-
14 September 2018
Aurobindo snaps up USbusinesses from SandozAurobindo is set to
become the second largest generics player in the US by number
ofprescriptions, and the second largest dermatology player in the
US, after agreeing toacquire Sandoz’ dermatology and oral solids
businesses in a deal worth US$1.0 billion.
Expected to close “in the course of 2019” following the
completion of customary closingconditions, including clearance from
the US Federal Trade Commission (FTC), the all-cashdeal includes an
upfront payment of around US$900 million, and another US$100
million inperformance-based earn-outs, financed through a
fully-committed debt facility. The acquiredbusinesses achieved
sales of US$1.2 billion in 2017.
Noting that deal would add approximately 300 products to
Aurobindo’s operations in theUS, including authorised generics,
in-licensed and branded dermatology products, “as well asadditional
development projects”, the Indian firm said its “market-leading,
vertically-integrated,highly-efficient manufacturing base” would
“enhance the position of the acquired portfolioover the medium
term”. Aurobindo will pick up certain operations from the former
FougeraPharmaceuticals dermatology business, as well as taking full
control of Sandoz’ Eon Labs unit.
“The portfolio being divested generated sales of [around] US$600
million in the first halfof 2018 for Sandoz,” Aurobindo revealed.
“After expiration of certain in-licensed productcontracts, and
rationalisations of acquired products that will not negatively
impact profitability –but before the impact of any potential
FTC-led divestments – the portfolio is expected togenerate over
US$900 million in sales for the first 12 months after completion of
the transactionfor Aurobindo.” No details on the acquired
businesses’ profitability were revealed by Aurobindo,which saw its
annual US Formulations sales increase by 9% to Rs74.4 billion.
Commercial and manufacturing capabilities in the US set to be
added through the dealinclude a “fully-dedicated dermatology sales
force”, along with three manufacturing facilities inthe US,
bringing “specialised capabilities in creams, ointments, lotions,
topical solutions andtopical suspensions that are highly
complementary to Aurobindo’s current manufacturingfootprint”.
Aurobindo says it and Sandoz will enter into a transitional
services agreement to“support the ongoing growth plans of the
businesses”. G
For Sandoz’ rationale and further details of the transaction,
turn to page 3.
Amgen launches first biosimilarAmgen says it has entered “fully
into the field of biosimilars” after announcing the launchof the
company’s first biosimilar; its Kanjinti (trastuzumab) version of
Roche’s Herceptinin Spain. “The comprehensive clinical data that
supported the authorisation of Kanjinti in Europeand now the
funding from [Spain’s] National Health System confirms the drug is
equivalent tothe reference product,” commented José Motellón,
medical director of Amgen Iberia.
“Amgen and [development partner] Allergan are working with local
markets to ensurethe timely launch of Kanjinti in Europe and intend
to make Kanjinti available to patients in theEuropean Union (EU),”
a spokesperson for Amgen told Generics bulletin. “We expect
tolaunch on a country-by-country basis with exact timing dependent
on each individual country.”The European Commission granted Amgen
an EU marketing authorisation for the oncologybiosimilar at the end
of May (Generics bulletin, 1 June 2018, page 5).
Commenting on the launch, Amgen said that not using its vast
knowledge in originalbiologics to develop and produce more
cost-effective biosimilars “would have been irresponsibleon our
part”. Amgen has a second oncology biosimilar approved in the EU,
Mvasi (bevacizumab),but the product has not yet been launched.
G
COMPANY NEWS 3
Teva tasks Nason to 3head TAPI business
Aurobindo deal gives Sandoz 3room to focus
Lupin in the clear on firm’s 4‘sartan’ drugs
Julphar hails progress 5despite sales decline
Licences and launches let 5JGL bounce back
Regional differences show 7Mylan’s potential
MARKET NEWS 8
Global bio reference comes 8under attack
US industry identifies a trinity 8of obstacles
EU switching is safe but 9needs more data
Canada should resist 9US trade proposition
REMS abuses in US cost 10US$13bn a year
FDA lists risk factors 11for facility inspections
France trials range of 11biosimilar incentives
PRODUCT NEWS 12
Celltrion wants lower 12RA criteria in the UK
Glenmark’s Seretide approved 13in Germany
Xbrane ‘shifts focus’ to 13biosimilar portfolio
Oracea ruling leaves 15Amneal waiting years
Alvogen’s gefitinib is 15approved in the EU
REGULARS
Events – Conferences and meetings 8Price Watch UK – Our regular
listing 13People – Albrecht hands over 16Stada to Goldschmidt
Issue No.368
Gen 14-9-18 Pgs.1-16.indd 1 11/09/2018 15:55
-
Recognisinnng the best in the globalgenerics aaand biosimilarsss
industries
Cocktail Reception &Awards Presentation
Tuesday 9 October 2018Palacio Municipal de CongresosMadrid,
Spain
Sponsor, Join us!Find out more about Sponsoring anAward and
Joining us on the night:
Visit: www.generics-bulletin.comEmail:
[email protected]
Call: +44 (0) 1564 777 550
Presented by In association with
Sponsored by
Gen 14-9-18 Pgs.1-16.indd 2 11/09/2018 15:55
-
3GENERICS bulletin14 September 2018
COMPANY NEWS
MANUFACTURING
Sun’s Halol gets observationsSun Pharma’s Halol formulations
manufacturing facility in Gujarat,India, is back under US Food and
Drug Administration (FDA)scrutiny, after receiving six ‘Form
483’observations.
Clarifying media reports, Sun revealed in a filing with the
BombayStock Exchange (BSE) that the observations pertained to a
pre-approval inspection at Halol that took place at the end of
August. “Thecompany will be submitting its response to the
observations to theFDA within 15 business days,” the Indian firm
noted.
After almost four years of compliance issues at Halol,
Sunreceived an establishment inspection report (EIR) from the FDA
forthe facility in June this year clearing the way for new product
approvals(Generics bulletin, 22 June 2018, page 3). G
BUSINESS STRATEGY
Teva tasks Nason tohead TAPI businessTeva’s senior
vice-president for European Technical Operations,John Nason, has
been appointed president of the Israeli firm’sstand-alone Teva
Active Pharmaceutical Ingredients (TAPI) businesswith additional
responsibility for the company’s Biologics operations.
In his new role, Nason, who joined Teva three years ago,
leadsthe company’s vertically-integrated business unit responsible
for thedevelopment, production, marketing and sales of bulk API for
boththird-party formulators and for Teva.
Referring to his European Technical Operations role, Teva
saidNason had “worked closely with the company’s commercial
andresearch and development (R&D) organisations to meet
customer andpatient needs while closely managing the
competitiveness of theproduct portfolio”. “In that position, Nason
was an active member ofthe operations leadership team responsible
for setting strategy andmanaging Teva’s global operations,” Teva
noted, “a role he will retainas president of TAPI and Teva’s
Biologics operations.”
Based at Teva’s global headquarters in Petach Tikva, Israel,
Nasonreports directly to Carlo de Notaristefani, executive
vice-president forTeva’s Global Operations. His previous employers
include Bristol-Myers Squibb and Novartis. G
BUSINESS STRATEGY
Civica is new non-profit in USAgroup of seven US healthcare
organisations representing around500 hospitals has realised plans
to form a non-profit genericscompany, as a means to tackle
shortages and address rising drug costs,officially establishing
itself as Civica Rx and naming former Amgenexecutive Martin
VanTrieste as its chief executive officer.
The number of representatives has risen since it was announced
inJanuary this year (Generics bulletin, 26 January 2018, page 3),
with“more than 120 health organisations representing about a third
of thenation’s hospitals” in the meantime having contacted Civica
Rx andexpressing a “commitment or interest in participating with
the new firm”.
“Civica Rx has identified 14 hospital-administered generic
drugsas the initial focus,” the company said. Headquartered in
Utah, Civica Rxexpects to have products on the market “as early as
2019”. G
MERGERS & ACQUISITIONS
Aurobindo deal givesSandoz room to focusSandoz plans to focus
more intently on “higher growth areas” inthe US to “achieve
sustainable and profitable growth”, includingcomplex generics,
value-added medicines and biosimilars, after agreeingto sell its
dermatology and oral solids businesses to Aurobindo in a dealworth
US$1.0 billion. “Through this transaction, we are refocusingour
business but also striving to ensure continuity of supply
ofimportant long-used generic medicines for patients and
customersin the US,” stated Sandoz’ chief executive Richard
Francis.
Complex generics on which Sandoz intends to focus, in terms
ofclinical development, business development and investment
efforts,include injectables, respiratory products and ophthalmics.
“Sharpening ourportfolio focus in the US allows us to devote more
time and resourcestoward our strategy,” said Francis, “creating
higher value and opening upaccess to important medicines where
alternatives are truly needed.”
Rumours have dogged Sandoz for months about the potential saleof
certain assets, amid steep price erosion in the US market.
Earlierthis year, parent company Novartis said it would “not
consider a firesale” for Sandoz’ US oral solids unit, “given it is
still profitable andhighly cash-generative” (Generics bulletin, 23
February 2018, page 3).
Through the agreed sale to Aurobindo, Sandoz will hand over
threemanufacturing facilities in the US: Fougera
Pharmaceuticalsdermatological facilities in Hicksville and
Melville, New York, alongsideSandoz’ dermatology development
centre; and the Eon Labs oral-solid dosage facility in Wilson,
North Carolina.
Around 750 employees in Hicksville, Melville and Wilson, aswell
as the field representatives for Fougera’s PharmaDerm
brandeddermatology business and Sandoz employees based in
Princeton,North Carolina, are expected to transfer to Aurobindo
upon closing.
“We recognise that the transfer of ownership for a business
ofthis size is a complex process, and we are aware that it may
createsome uncertainties for our associates in the US,”
acknowledged CarolLynch, Sandoz’ US president. “It is thus a
priority for us to make thetransition as clear and quick as
possible.”
From a portfolio of around 300 products, Aurobindo will gain
accessin the generic dermatology portfolio to a “wide range of
therapeuticareas”, including topical antibiotics, gynaecological
and dermatologicalantifungal agents, anti-acne agents, local
anaesthetic analgesics, anti-itch, and a dermatological
chemotherapeutic agent. For the oral non-dermatological basket of
products, therapeutic categories includeautoimmune disease
treatments, oncology drugs and hormones.
“The acquisition enhances Aurobindo’s market leading pipeline
ofabbreviated new drug application (ANDA) filings with
additionalpipeline projects, including ANDAs that have already been
filed,products under development, and first-to-file opportunities
whichhave the potential to be exclusive,” Aurobindo noted.
“We expect a seamless integration of the acquired businesses
withthe rest of the Aurobindo group given the success we have
achievedin our acquisitions to date,” commented N Govindarajan,
Aurobindo’smanaging director. “We will be focused on leveraging our
group’smarket-leading vertically-integrated and highly efficient
manufacturingbase to enhance the market position and medium-term
profitabilityof the businesses we are acquiring.”
Jefferies, which acted as financial advisor to Aurobindo, said
thatthe deal “represents the largest out-bound merger and
acquisition(M&A) transaction by an Indian pharma company and
would provideAurobindo a meaningful entry into the US dermatology
space”. Gn [email protected]
Gen 14-9-18 Pgs.1-16.indd 3 11/09/2018 15:55
-
4 GENERICS bulletin 14 September 2018
COMPANY NEWS
[email protected]
Issue 368 l 14 September 2018
Director of Subscriptions: Val Davis Group Sales Manager: Rob
Coulson
Awards Manager: Natalie Cornwell Production Controller:Debi
Robinson
Head of Pharma: Mike Ward Managing Director: Philip Jarvis
l General enquiries: [email protected] l Subscription
enquiries: [email protected]
l Editorial enquiries: [email protected] l
Advertising enquiries: [email protected]
Editor: Aidan Fry
[email protected]
Deputy Editor: David Wallace
[email protected]
Assistant Editor: Dean Rudge
[email protected]
Business Reporter: Grace Montgomery
Terms & Conditions: See
www.generics-bulletin.com/subscribe.While due care has been taken
to ensure the accuracy of information contained in this
publication,the publisher makes no claim that it is free of error
and disclaims any liability whatsoever for anydecisions or actions
taken as a result of its contents.
Published by OTC Publications Ltd, 4 Poplar Road, Dorridge,
Solihull B93 8DB, UK.Tel: +44 (0) 1564 777550 Fax: +44 (0) 1564
777524Company registered in England No 02765878.© OTC Publications
Ltd. All rights reserved.Generics bulletin® is registered as a
trademark in the European Community.Printed by Warwick Printing
Company Ltd. ISSN 1742-0784
MANUFACTURING
Lupin in the clear onfirm’s ‘sartan’ drugsValsartan active
pharmaceutical ingredient (API) manufactured byLupin is “safe” with
“no chance” of containing the toxic impurityfound in some other
valsartan active ingredients, an inspection ofone of the Indian
firm’s facilities by US regulators has confirmed.
Lupin’s announcement followed the US Food and DrugAdministration
(FDA) completing a current good manufacturing(cGMP) inspection at
the firm’s Tarapur manufacturing site inMaharashtra, India,
conducted from 27-31 August by three agencyinvestigators. “The
inspection closed with one observation, a proceduraldeficiency,”
the Indian firm noted, releasing no further details.
As well as valsartan, the inspection had focused on the safety
oftwo other ‘sartan’ APIs, losartan and irbesartan. All three drugs
arein the angiotensin II receptor blocker (ARB) therapeutic class,
usedto treat high blood pressure.
In July, the FDA announced that low levels of the
impurityN-nitrosodimethylamine (NDMA), which can cause cancer, had
beenfound in valsartan API manufactured by a Chinese supplier,
leadingthe FDA to issue recalls (Generics bulletin, 27 July 2018,
page 17).
Follows global valsartan recallsValsartan finished-dose drugs,
including combination products,
using API made by Zhejiang Tianyu were affected by the
recall.Regulators across the globe, including in Canada and Europe,
havealso acted, with NDMA classified a probable human
carcinogen.
Referring to the inspection at Tarapur, Lupin underlined
that,“during the inspection, the FDA concluded that manufacturing
processesof Lupin sartans are safe with no chance of presence of
the NDMAimpurity in the APIs”.
Earlier this month, the FDA announced that a “major
operation”was underway to investigate and address the “troubling
finding”,leading the agency to also test all ARBs for traces of the
toxic material(Generics bulletin, 7 September 2018, page 15). The
US agencymaintained that it was still not “100 percent sure” what
the root causeof the impurity was, noting that full understanding
would require“correlation of multiple test results from valsartan
APIs made bydifferent processes with the various process steps used
by differentmanufacturers or at different times”.
The European Directorate for the Quality of Medicines
(EDQM)recently took further action on valsartan API suppliers (see
page 12). G
CONCORDIA INTERNATIONAL has completed its
recapitalisationtransaction that reduces the Canadian firm’s total
debt by aroundUS$2.4 billion and its annual cash interest expense
by about US$170million. In return for a US$586.5 million private
placement, investorshave received 87.69% of the firm’s voting
shares, with existingshareholders getting just one share for each
300 they previouslyheld. The deal gives Concordia approximately
US$200 million ofunrestricted cash on hand. “We have an enviable
global specialtygenerics platform, and will be seeking both organic
and inorganicgrowth opportunities to leverage this platform to its
full potential,”chief executive officer Graeme Duncan
maintained.
JB CHEMICALS & PHARMACEUTICALS has secured boardapproval for
a share buy-back of up to 9.46% of the Indian firm’sequity for an
amount not exceeding Rs1.30 billion (US$18.1 million).
AVARA PHARMACEUTICAL SERVICES has completed its purchaseof
Sandoz’ injectables facility in Boucherville, Canada. The
contractdevelopment and manufacturing organisation (CDMO) had
struckthe deal earlier this year (Generics bulletin, 1 June 2018,
page 3).
AMPAC FINE CHEMICALS is now part of South Koreanconglomerate SK
Holdings after the active pharmaceutical ingredient(API) producer
completed its transition from its previous owner,private-equity
firm HIG Capital, announced earlier this year(Generics bulletin, 27
July 2018, page 3).
CSPC PHARMACEUTICAL said its “common generic-drug
businessincreased market penetration” and its “bulk-drug business
keptmarket-leader position” as the Hong Kong-based company
increasedits turnover by 49.8% to HK$10.8 billion (US$1.37 billion)
in thefirst half of this year. That total included common generics
salesahead by 42.3% to HK$3.31 billion as the firm’s
azithromycin,captopril and tramadol tablets passed consistency
evaluations.
INTAS PHARMACEUTICALS increased its turnover by 30.6% toRs109
billion (US$1.52 billion) in its financial year ended 31 March2018.
The privately-owned Indian group – which operates under theAccord
name in Europe and North America – improved its profitbefore
interest, tax and depreciation by 39.3% to Rs24.6 billion.
GRINDEKS has formed a “strategic long-term co-operation” ondrug
research and development with the Latvian Institute of
OrganicSynthesis. The agreement replaces a current partnership that
focuseson individual research projects, such as into cardiovascular
drugs.G
IN BRIEF
Gen 14-9-18 Pgs.1-16.indd 4 11/09/2018 15:55
-
5GENERICS bulletin14 September 2018
COMPANY NEWSFIRST-HALF RESULTS
Julphar hails progressdespite sales declineJulphar says it has
made “significant progress in the GulfCo-Operation Council (GCC)
and North Africa” even as the UnitedArab Emirates (UAE)-based group
posted a 4% sales fall to AED558million (US$152 million) in the
first half of this year. However,second-quarter sales advanced by
19% to AED294 million.
Highlighting the “solid financial results”, general manager
JeromeCarle described the first six months of 2018 as “a busy but
veryproductive period”. “We saw an acceleration of our revenue in
theLevant region in the second quarter and continue to improve on
lastyear’s performance,” he commented. “Our subsidiaries, led by
GCCand Egypt, are also delivering strong performances locally.”
“We have made significant progress in North Africa by
deliveringstrong results in Libya and Morocco,” Carle continued,
noting that
the firm had also “divested several non-strategic assets” during
thesecond quarter that would improve its cash-flows and enable it
to focusmore clearly on core operations.
“We have just launched several new products in key
therapeuticareas, such as cardiovascular, and our expansion plans
are on track,particularly in Saudi Arabia and Africa, where we are
making inroadsin a number of key markets,” he explained.
As Figure 1 shows, Julphar’s first-half sales shortfall was
duepredominantly to turnover in Saudi Arabia – where the firm holds
a51% stake in the Julphar Saudi Arabia venture – tumbling by
nearlya third to AED124 million, and to a lesser extent to a 2%
slip to AED134million in the UAE-based group’s domestic market.
With 25 product launches planned in the UAE this year, and200
product registrations scheduled in the region, Carle maintainedthat
continued investment in its pipeline and expansion in key
marketswould “keep Julphar on track to return to sustainable growth
in linewith its targets”.
“Our balance sheet looks stronger as we continue to reduce
ourlong-term debts and manage our working capital position,” he
stated.Having seen its first-half gross margin weaken by just over
10percentage points to 39.1%, Julphar – which is also known as
GulfPharmaceutical Industries – posted a 22% slide in operating
profit toAED57.6 million. But second-quarter operating profit
climbed by43% to AED35.6 million. G
Region First-half sales(AED millions)
Change(%)
Proportionof total (%)
Synthesis 541 +65 10
Ingredients 190 +29 4
Finished doses 51 +919 1
Julphar 557.6 -4 100Figure 1: Breakdown of Julphar’s sales in
the first half of 2018 (Source – Julphar)
FIRST-QUARTER RESULTS
API gains boost Ipca’s salesA27% rise in turnover from active
pharmaceutical ingredients(APIs) contributed to Ipca Laboratories
increasing its groupturnover by just over a fifth to Rs8.68 billion
(US$121 million) inits financial first quarter ended 30 June 2018.
Exports of APIs climbedby 17% to Rs1.58 billion, while the Indian
company’s domestic salesof bulk drugs shot up by two-thirds to
Rs600 million (see Figure 1).
India was the driving force behind Ipca’s total Formulations
salesadvancing by 18% to Rs6.25 billion. Domestic sales ahead by
36%to Rs4.01 billion more than compensated for Formulations
exportssliding by 5% to Rs2.24 billion despite stronger
institutional sales.
Holding cost of materials consumed steady, despite the
salesgrowth, enabled Ipca to bounce back from a prior-year pre-tax
lossof Rs212 million to post a pre-tax profit of Rs782 million.
G
Business segment First-quarter sales(Rs millions)
Change(%)
Proportionof total (%)
India 4,009 +36 46
Exports 2,240 -5 26
Formulations 6,249 +18 72
India 600 +66 7
Exports 1,577 +17 18
APIs 2,178 +27 25
Others 249 +48 3
Ipca 8,676 +21 100
Figure 1: Breakdown by business segment and region of Ipca
Laboratories’ salesin its financial first quarter ended 30 June
2018 (Source – Ipca)
BUSINESS STRATEGY/FIRST-HALF RESULTS
Licences and launcheslet JGL bounce backStarting to sell in 17
new markets through partners and business-to-business deals while
launching 28 products itself helped Croatia’sJGL to significantly
reduce its pre-tax loss in the first half of 2018.The firm also
almost halved its net debt to earnings before interest,tax,
depreciation and amortisation (EBITDA) ratio from 7.98 to 4.27.
Growth in Croatia and Ukraine, as well as in Russia – where
theOTC specialist increased its market shares for key brands like
theAqua Maris and Meralys nasal sprays, and also “successfully
completed”an inventory reduction process – pushed up sales by JGL’s
core Pharmabusiness by around a quarter to CrK269 million (US$42.1
million).
In Croatia, JGL “grew faster than the market” for OTC
products,helping to compensate for the “constant pressures on
prescription drugprices”. Turnover in Ukraine nearly doubled amid a
market recovery.
Russia accounted for two-fifths of JGL Pharma’s first-half
sales,Croatia 22% and Ukraine 5%, with another 11% derived from
business-to-business licensing. Viewed by product, Aqua Maris made
up 32%or CrK86.9 million, of sales, followed by Dramina
(dimenhydrinate)with CrK22.3 million, Meralys with CrK18.9 million
and Vizol S(ectoin) eye drops with CrK6.7 million.
Including Pablo pharmacies, group turnover grew by a fifth
toCrK349 million. Hailing the “excellent sales results”, chief
executiveofficer Mislav Vučić insisted that the group would persist
with its“chosen path of transformation”. Having bounced back to
profitabilityat EBITDA level, JGL cut its pre-tax loss by 70% to
CrK20.7 million.G
TJOAPACK is partnering with UK-based technology firm Veratrak
to“establish the use of blockchain across the pharmaceutical
industry”.The two firms believe the technology can improve the
pharma supplychain. Netherlands-based contract packager Tjoapack
has also launcheda postponement packaging service whereby patient
informationleaflets and national legislative requirements are
implemented aslate as possible to meet local demand. G
IN BRIEF
Gen 14-9-18 Pgs.1-16.indd 5 11/09/2018 15:55
-
Gen 14-9-18 Pgs.1-16.indd 6 11/09/2018 15:55
-
7GENERICS bulletin14 September 2018
COMPANY NEWS
Figures 1-4: Breakdown of Mylan’s second-quarter product sales
totalling US$2.76 billion by therapeutic franchise, shown in each
of its three operating regions andglobally (Source – Mylan)
Central Nervous System &AnaesthesiaUS$220.7m
InfectiousDisease
US$58.2m
Respiratory &Allergy
US$129.4m
CardiovascularUS$149.1m
GastroenterologyUS$145.1m
Diabetes &MetabolismUS$80.2m
DermatologyUS$74.3m
Women’sHealthcareUS$66.8m
OncologyUS$18.4m
ImmunologyUS$2.5m
OtherUS$45.9m
Europe
Central Nervous System &AnaesthesiaUS$76.4m
InfectiousDisease
US$251.6m
Respiratory & AllergyUS$53.7m
CardiovascularUS$46.2m
GastroenterologyUS$92.1m
Diabetes &MetabolismUS$33.5m
DermatologyUS$27.2m
Women’sHealthcareUS$22.2m
OncologyUS$32.8m
ImmunologyUS$10.7m
OtherUS$117.7m
Rest of World
Central Nervous System &AnaesthesiaUS$497.0m
InfectiousDisease
US$372.4m
Respiratory &Allergy
US$364.7mCardiovascularUS$271.4m
GastroenterologyUS$271.1m
Diabetes &MetabolismUS$227.8m
DermatologyUS$186.0m
Women’sHealthcareUS$174.2m
OncologyUS$153.4m
ImmunologyUS$27.3m
OtherUS$210.2m
Mylan
Considerable regional variations in the balance of Mylan’s
saleswhen measured by therapeutic franchise suggest that the
globalplayer still has local portfolio gaps that could be
filled.
For example, oncology drugs accounted for US$153 million,
or5.6%, of the company’s total product sales in the second quarter
ofthis year that decreased by 6% to US$2.76 billion, excluding
US$52.8million of ‘other’ revenues (Generics bulletin, 31 August
2018,page 3). But the bulk of that oncology total came from the US,
wheresales of US$102 million made up just over a tenth of the
regionaltotal (see Figure 1).
By contrast, cancer therapies made up less than 2% of all
Mylanproduct sales in Europe, with oncology sales of just US$18.4
millionin the three-month period (see Figure 2).
Brands including EpiPen (epinephrine) and its authorised
generic,as well as Perforomist (formoterol fumarate), ensured that
respiratoryand allergy medicines made up well over a sixth of North
Americanproduct sales. That proportion could increase substantially
if Mylansucceeds in bringing a generic of Advair Diskus
(fluticasone/salmeterol) to the US market. Having responded to
issues raised by
the US Food and Drug Administration (FDA), Mylan has an
FDAaction date for its substitutable generic in mid-October this
year(Generics bulletin, 31 August 2018, page 19).
CNS and anaesthesia leadCentral nervous system (CNS) and
anaesthesia drugs were
responsible for at least a fifth of product sales in both
Mylan’s NorthAmerica and Europe regions during the second quarter,
but only a tenthof turnover in its Rest of World region. With the
latter encompassingmost emerging markets and developing countries,
nearly a third of Rest ofWorld sales came from treatments for
infectious diseases (see Figure 3).
On a global basis, treatments for infectious diseases and
forrespiratory and allergy complaints each contributed more than
13%of total product sales (see Figure 4).
Mylan is currently “evaluating a wide range of alternatives”
forits business amid “negative trends and dynamics” that it sees
as“unsustainable for the US healthcare system” (Generics
bulletin,10 August 2018, page 1). Gn
[email protected]
BUSINESS STRATEGY/SECOND-QUARTER RESULTS
Regional differences show Mylan’s potential
Central Nervous System &AnaesthesiaUS$199.9m
InfectiousDisease
US$62.6m
Respiratory &Allergy
US$181.6m
CardiovascularUS$76.1m
GastroenterologyUS$33.9m
Diabetes &MetabolismUS$114.1m
DermatologyUS$84.5m
Women’sHealthcareUS$85.2m
OncologyUS$102.2m
ImmunologyUS$14.1m
OtherUS$46.6m
North America
Gen 14-9-18 Pgs.1-16.indd 7 11/09/2018 15:55
-
8 GENERICS bulletin 14 September 2018
FDA BIOLOGICS HEARINGREGULATORY AFFAIRS
Global bio referencecomes under attackMoves to facilitate
biosimilar development by encouraging theUS Food and Drug
Administration (FDA) to accept non-UScomparator drugs came under
attack from originators’ body PhRMAduring an FDA public hearing on
biologics competition and innovation.
“PhRMA is concerned with proposals to waive
bridging-studyrequirements based on non-public information where a
non-UScomparator is produced at the same facility as the reference
product,”stated the association’s vice-president of intellectual
property and law,David Korn. Only if biosimilar applicants could
use “publicly availableinformation” to demonstrate that the non-US
reference drug had “thesame drug substance, dose, dosage form, and
route of administrationas the US reference product”, as was made
using the same cell line,should bridging-study requirements be
waived, he argued.
“In cases where this information is a trade secret, FDA
relianceon these trade secrets, or disclosure of them to the
biosimilar developereither explicitly or implicitly through waiver
of a bridging-studyrequirement, would raise serious issues under
federal law and thetakings clause,” Korn warned.
Shortly beforehand, Christine Simmon – executive director atthe
Biosimilars Council within the Association for Accessible
Medicines(AAM) – had expressed strong support for “eliminating the
requirementfor sponsors to conduct expensive and unnecessary
bridging studieswhen using a non-US-licensed reference
product”.
“We are concerned that some aspects of the FDA’s draft
guidanceon interchangeability impose unnecessarily burdensome
scientificstandards on interchangeability determinations or may be
inconsistentwith statutory requirements,” Simmon said, adding that
such standardscould deter biosimilar development programs, thereby
significantlyaffecting patient access. G
REGULATORY AFFAIRS
Originators query switchingOne interchangeable biosimilar should
not be substituted for anotherin the US, and US Food and Drug
Administration (FDA) guidanceshould reflect that, several biologics
originators argued during an FDApublic hearing on biologic
competition and innovation. The same pointwas echoed by the
originator-backed Alliance for Safe BiologicMedicines (ASBM).
AbbVie’s Nathan Doty described switching between
interchangeablebiosimilars of the same reference brand as “not
scientifically justifiable”due to structural differences that could
“induce immunogenicity whenpatients are switched between them”.
“You cannot predict in advancewhat differences might prompt an
immune response,” he argued.
Similarly, Janssen’s Andrew Greenspan urged the FDA to
“addressbiosimilar-to-biosimilar switching”, as Veterans Affairs
hospital ashad done with different brands of infliximab. “The FDA
should considermethods of obtaining post-marketing data about
biosimilar-to-biosimilarswitching,” he advised. Absent such data,
he demanded that biosimilarlabelling convey the lack of switching
data and that, if interchangeable,that interchangeability was only
with the reference product.
Urging the agency to finalise its draft interchangeability
guidance,trade body BIO’s executive vice-president for emerging
companies,Cartier Esham, insisted clinical switching studies were
essential forpharmacy-level substitution. G
PRICING & REIMBURSEMENT/INTELLECTUAL PROPERTY
US industry identifiesa trinity of obstaclesReimbursement
issues, patent tactics to extend monopolies and“unwarranted
restricted access to reference products” are the threebiggest
obstacles to biosimilars reaching the hands of healthcareproviders
and patients in the US, Christine Simmon, executive director ofthe
Biosimilars Council within the Association for Accessible
Medicines(AAM), told a US Food and Drug Administration (FDA) public
hearing.
Addressing the hearing on facilitating biologic competition
andinnovation, Simmon pointed out that FDA approval was no
guaranteeof biosimilar availability. “You might believe that I have
just namedthree things the agency can’t do anything about – we
would disagree,”she told the FDA. “The FDA is more than a regulator
of biosimilars.”
On reimbursement, Simmon encouraged the FDA to work withthe US
Department of Health and Human Services (HHS) and itsCenters for
Medicare and Medicaid Services (CMS) to promote low-cost biologics
by addressing barriers to access created by rebate trapsand
exclusionary contracting.
Originators manipulating intellectual-property provisions to
procure‘patent thickets’ remained “a primary reason” approved
biosimilarswere not being launched, she highlighted. The
“exorbitant cost oflitigating meritless patents” was chilling
competition, she said inurging the FDA to work with the US patent
and Trademark Office(USPTO) not only to “stem the issuance of
non-innovative patents”but also to support the use of inter partes
reviews that gave biosimilardevelopers “an earlier and more
accurate picture of the patent landscapein a timely and less
expensive manner”.
While Simmon said the Biosimilars Council and AAM appreciatedthe
FDA’s move to name originators that were blocking access tosamples
needed for biosimilarity testing, they were “not aware of
anycompanies that have changed their practices as a result of the
FDA’snaming and shaming”. Pointing to a report that the AAM had
justcommissioned that showed the cost of restricted access to
samples tobe over US$13 billion per year (see page 10), she
insisted passing theproposed Creating and Restoring Equal Access to
Equivalent Samples(CREATES) Act would force originators to change
their behaviour.
Supporting Pfizer’s recent citizen petition that seeks to
combatmisinformation on biosimilars (Generics bulletin, 7 September
2018,page 9), Simmon said several statements around ‘non-medical
switching’ignored both routine physician-led switching between
biologics inthe US and extensive data from Europe. G
REGULATORY AFFAIRS
Gottlieb promises FTC actionThe US Food and Drug Administration
(FDA) is working closelywith the US Federal Trade Commission (FTC)
to address anti-competitive behaviour on biological drugs, FDA
Commissioner ScottGottlieb told a public hearing. “We will be
taking some steps inconjunction with them in the coming months,” he
heralded.
The biosimilars action plan that the agency recently unveiled
wasintended not only to make the biosimilar development and
reviewprocess “more efficient and predictable”, it was also aimed
at improvingcommunication with patients, physicians and payers,
Gottlieb explained(Generics bulletin, 27 July 2018, page 9). “Our
action plan is dynamic,and we continue to evaluate additional FDA
actions that are needed toshape the appropriate balance between
innovation and competition”. G
Gen 14-9-18 Pgs.1-16.indd 8 11/09/2018 15:55
-
9GENERICS bulletin14 September 2018
MARKET NEWS
Bachem is the leading independentsupplier of active
pharmaceuticalingredients (APIs) for the human andveterinary
pharmaceutical market.
• Atosiban• Glucagon• Goserelin Acetate• Lanreotide• Leuprolide
Acetate• Octreotide Acetate• Teriparatide Acetate• Tetracosactide•
Triptorelin Acetate• (Arg8)-Vasopressin Acetate
www.bachem.com
MEET US ATCPhI WORLDWIDE 2018BOOTH 8B20
INTELLECTUAL PROPERTY
Canada should resistUS trade propositionCanada’s government must
resist proposals from the US that wouldsee restrictive and onerous
intellectual-property provisionsintroduced as part of a trade deal
between the two countries, theCanadian Generic Pharmaceutical
Association (CGPA) has warned.
Commenting on the resumption of trade negotiations betweenthe US
and Canada – shortly after the US and Mexico struck
anagreement-in-principle that would include 10 years of data
exclusivityfor biologics (Generics bulletin, 7 September 2018, page
1) – CGPApresident Jim Keon said the association understood that
“there aremany US proposals on the table that would require changes
to Canadianlaw and delay competition from generic and biosimilar
medicines,including longer periods of data protection for biologic
drugs”.
“If such proposals were adopted, they would create billions
ofdollars in new costs for employers who sponsor employee drug
benefitprograms, governments, and patients who pay for medicines
out ofpocket,” Keon warned. “It is our understanding that the
measurespursued by the US in the negotiations go far beyond the
measuresincluded in the Comprehensive Economic and Trade
Agreement(CETA) with the European Union,” he added, “and would be
far moreharmful for Canadians if adopted.”
“Canada must not agree to North American Free Trade
Agreement(NAFTA) concessions that reduce access to essential
medicines andincrease costs for those who pay for drugs,” Keon
concluded. G
REGULATORY AFFAIRS
EU switching is safebut needs more dataCollaborative switching
studies are needed across Europe to help“clarify all aspects of
switching to biosimilars”, according to astudy that has just been
published in the European Medical Journal.Acknowledging that data
on switching from a brand biologic to itsbiosimilar suggest that
“switching is not detrimental for patients bothin terms of safety
and efficacy”, Syneos Health’s ‘overview of theEuropean experience’
nevertheless suggests that “large-scale andlong-term data are
warranted to provide a more robust assessment”.
Numerous switching studies – including high-profile and
large-scale examples such as Norway’s NOR-SWITCH study – had led
toan “overall conclusion…that switching to the biosimilar product
didnot raise special concerns in terms of either efficacy or
safety”, theoverview points out. However, a “nocebo” effect –
whereby negativepatient perceptions cause an unexpected and
unexplained worseningin treatment outcomes – was cited as a
potential reason for a tendencytowards higher discontinuation rates
following switches.
“It is of fundamental importance to collect real-world data
derivedfrom large-scale observational or registry studies,” the
report insists,recommending that “specific collaborative switching
programmesshould be implemented that involve all stakeholders, with
physiciansmaintaining a leading role”. Moreover, “a communication
strategyinvolving the patient and all other stakeholders that
focuses on thepatient’s specific circumstances... will play a
crucial role”. G
Gen 14-9-18 Pgs.1-16.indd 9 11/09/2018 15:55
-
10 GENERICS bulletin 14 September 2018
MARKET NEWS
9-11 Octobern CPhI Worldwide
Madrid, SpainCPhI Worldwide offers an exhibition and networking
opportunities.Running alongside this event will be the ICSE,
InnoPack, P-MECand Finished Dosage Formulation exhibitions.
Contact: UBM Information. Tel: +31 20 708 1637.E-mail:
[email protected]. Website www.cphi.com.
22-23 Octobern Next Steps: Manufacturing &
Quality WorkshopMaryland, USAThis event, organised by the
Association of Accessible Medicines(AAM), will provide information
on manufacturing and qualitycomponents of generics and biosimilars
businesses.
Contact: AAM. Tel: +1 202 249 7127.E-mail:
[email protected]. Website
www.accessiblemeds.org.
24-26 Octobern 21st APIC/CEFIC European Conference
Budapest, HungaryThis conference will discuss the latest
development in the field ofGMP and regulatory compliance.
Contact: Concept Heidelberg. Tel: +49 6221 84 44-0.E-mail:
[email protected]. Website www.api-conference.org.
29-30 Octobern World Biosimilar Congress
Basel, SwitzerlandThere will be networking receptions and
lunches, an exhibitionand a conference included in this event.
Contact: Terrapinn. Tel: +44 207 092 1257.E-mail:
[email protected]. Website www.terrapinn.com.
21 Novembern 2nd Value Added Medicines Conference
Brussels, BelgiumOrganised by Medicines for Europe, this one-day
event will look atopportunities presented by value added medicines
across the industry.
Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail:
[email protected]. Register online
atwww.medicinesforeurope.com/events.
26-27 Novembern EuroPLX 68
Athens, GreeceThis two-day meeting provides an opportunity to
discuss andnegotiate agreements, development, in-licensing,
marketing,promotion and distribution.
Contact: RauCon. Tel: +49 6221 426296 0.E-mail:
[email protected]. Website: www.europlx.com.
EVENTS – October – November
9 October 2018
Sponsor,Join us!
[email protected] www.generics-bulletin.comCall: +44
1564 777550
Palacio Municipal de Congresos,Madrid, Spain
REGULATORY AFFAIRS
REMS abuses in UScost US$13bn a yearMore than US$13 billion in
annual lost savings stems from brandindustry abuses of Risk
Evaluation and Mitigation Strategies(REMS) and safety programs in
the US, according to a Matrix GlobalAdvisors study commissioned by
the country’s Association for AccessibleMedicines (AAM). Matrix
Global Advisors chief executive Alex Brillsaid the findings were
“conservative”, adding that “absent congressionalaction, these
costs can be expected to increase”.
Noting that this figure represented “an increase of 250% in
thelast four years”, the AAM said that such abuses – revolving
largelyaround brand companies using risk programs as a pretext to
denysamples to generics firms that are needed to conduct studies
requiredfor US Food and Drug Administration (FDA) approval – “can
beexpected to affect more biosimilars as their development
increases”.
“Unfortunately, withholding samples is an accepted
businesspractice for some as a means to artificially protect and
extend theirmonopolies beyond what Congress intended,” commented
AAMpresident and chief executive officer Chip Davis. “That is why
Congressmust pass the bipartisan Creating and Restoring Equal
Access toEquivalent Samples (CREATES) Act.”
According to the study, the total US$13.4 billion figure in
unrealisedsavings includes US$5.8 billion for private insurers,
US$5.2 billionfor the federal government and US$1.8 billion for
consumers.
“Of the total US$13.4 billion in lost savings, US$3.1 billion
isattributable to products restricted by REMS, and US$10.3 billion
toproducts with non-REMS restrictions created by brand
manufacturers,”the study states.
The AAM pointed out that FDA Commissioner Scott Gottliebhad
already highlighted the importance of the issue, when he last
yearcalled on originators to “end the shenanigans” (Generics
bulletin,17 November 2017, page 11), while the FDA publicly
released a‘name and shame’ list earlier this year of “access
inquiries” relatingto difficulties experienced by generics firms in
obtaining samplesfor development (Generics bulletin, 25 May 2018,
page 9).
And at a recent FDA hearing on ‘facilitating competition
andinnovation in the biological products marketplace’ (see page 8),
AAMsenior vice-president of policy and strategic alliances
ChristineSimmon – who is also executive director of the AAM’s
BiosimilarsCouncil – pointed to the harmful effects of REMS
abuses.
“As biologic spending continues to grow,” Simmon said,
“restrictedaccess schemes will have an increasingly harmful effect
on potentialcost-saving biosimilar competition.” Noting that there
were currently“more than 60 biosimilar development programs
underway, promisingnew savings and access for patients”, Simmon
warned that “withoutaccess to samples of the brand reference
products, it is simply impossiblefor biosimilar manufacturers to
develop more affordable alternativesto what is currently available
to America’s patients”.
Separately, a report by I-MAK highlighted by the AAM haspointed
out the scale of “excessive pharmaceutical patenting”
byoriginators. According to the ‘Overpatented; Overpriced’ report,
thetop 12 branded drugs on the US market last year are protected by
atotal of 848 patents, or an average of 71 per drug.
“We are increasingly seeing evidence of how the patent systemis
being used to tip the balance and delay patient access to a point
wellbeyond what Congress intended,” the AAM commented, pointing
inparticular to Humira (adalimumab) with 132 patents that
blockedcompetition for up to 39 years. Gn
[email protected]
Gen 14-9-18 Pgs.1-16.indd 10 11/09/2018 15:55
-
11GENERICS bulletin14 September 2003
MARKET NEWS
Drug Delivery Solutions Pvt Ltd
OperationsEuropeRest of World
: [email protected]: [email protected]
Get in [email protected]
Racecadotril 10,30 mgTaste Masked Granules in Sachet
Athena has an EU GMP approved facility forGranules, Tablets,
Capsules & Sachet lines.
EU dossiers ready for DCPDomperidone 10 mg ODTFenofibrate 160 mg
Tablet, 160,200,267 mg CapsuleLevocetirizine 5 mg ODTMeloxicam
7.5,15 mg ODTMetformin 750 mg SR TabletOndansetron 4,8 mg
ODTPrednisolone 5,10 mg Soluble TabletTramadol + Paracetamol 37.5 +
325 mg Tablet & ODTVitamin D3 400, 800, 1K, 25K, 50K IU
ODTZolpidem 5,10 mg Sublingual & ODT
Bioequivalent to Tiorfan® Bioprojet France
REGULATORY AFFAIRS
France trials range ofbiosimilar incentivesFrench legislation
setting out an ‘experiment’ to trial several differentmethods of
incentivising biosimilar prescription in hospitals has beenwarmly
welcomed by local generics and biosimilars association Gemme.
Published in France’s Journal Officiel, the detailed decree
setsout a plan that has been developed with local health insurer
CNAMand will run for three years from 1 October 2018. Its stated
objectiveis to “test a new incentive mechanism to encourage and
promoteprescribing of biosimilar medications” for hospital
prescriptionsthat are dispensed by community pharmacies, to “find
the best wayto promote the development of biosimilars”. Etanercept
and insulinglargine will be the focus of these efforts.
“The principal objective of this experiment is to achieve a
morerapid rise of at least 15 points in biosimilar prescribing,”
the legislationstates, with a maximum of 40 healthcare
establishments participatingin the experiment. In the interests of
balance, around 16 universityhospitals and three private
establishments will be included amongthe total number of
establishments.
Various incentive mechanisms are outlined in the text,
including“innovative financial models” that adopt a gainsharing
approach, aswell as “innovative organisational models” that cover
the structureof healthcare professionals as well as the use of
digital tools to boostbiosimilar prescribing. Meanwhile, ways of
“improving the efficiencyand quality of procurement” are also set
out by the document.
Ultimately, the legislation states, the goal of promoting
biosimilaruptake is to stimulate competition and give healthcare
establishmentsenhanced negotiating power when buying from
suppliers.
Taking into account the expected costs of the experiment,
netsavings of around C6 million (US$7 million) for health insurers
areexpected in 2018, the decree states, with a further C12 million
tofollow in 2019 and 2020. In 2018, the legislation notes, the
figurewill contribute to an overall C40 million savings goal set
out in France’slatest healthcare budget that is linked to
developing biosimilars(Generics bulletin, 6 October 2017, page
4).
A “periodic review” of progress will take place, with a
finalevaluation published in early 2022 at the latest. Evaluation
methods willinclude comparing the evolution of biosimilar
penetration rates over thecourse of the experiment, in both
participating and non-participatinghealthcare establishments.
Meanwhile, “qualitative” evaluation methodswill include
questionnaires and focus groups for participating doctorsthat will
address practical aspects of the experiment as well as
evaluatingtheir knowledge and experience of biosimilars.
Local industry association Gemme, which has long campaignedfor
government policy proposals to bolster the biosimilars market
inFrance, responded positively to the experiment. “Gemme
welcomesthe publication of this decree,” the association told
Generics bulletin,noting that it “translates, through an initial
experiment, the will of thegovernment to develop biosimilars in
France”. Furthermore, Gemmeadded, “we would like to see other
similar experiments in the future”.
France recently set a goal of achieving 80% biosimilar
penetrationfor individual molecules within their markets by 2022 as
part of abroader five-year healthcare strategy (Generics bulletin,
12 January2018, page 1). After last year setting out a list of 11
similarity groupsshowing which biosimilars correspond to certain
brand biologics(Generics bulletin, 10 November 2017, page 11),
local medicinesagency ANSM recently added a further three reference
brands tothe list (Generics bulletin, 7 September 2018, page 13).
Gn [email protected]
REGULATORY AFFAIRS
FDA lists risk factorsfor facility inspectionsFacilities’
compliance history, their recalls history and the “inherentrisk” of
the drugs made at the plant are all factors that that the USFood
and Drug Administration (FDA) should take into account whendeciding
which sites to visit for routine current good manufacturingpractice
(cGMP) surveillance inspections. Other factors listed in anew
manual of policies and procedures (MAPP), effective from
26September, are whether the site has been inspected within the
pastfour years and any inspections conducted by overseas
authorities.
This internal policy forms part of the US commitment to
“providegreater transparency regarding prioritisation and
scheduling ofinspections”, as well as to communicate information
following audits,under the revised Generic Drug User Fee Amendments
(GDUFA II).
Efforts include updating the agency’s publicly available
inspectionclassifications database, communicating with foreign
regulatoryauthorities regarding the compliance status of
establishments, providinginformation on the agency’s risk-based
site selection model, andcommunicating information from inspections
that may impactapprovability to applicants and facility owners.
FDA Commissioner Scott Gottlieb noted that the agency had
alsopursued opportunities to collaborate with other countries. The
FDAalso recently updated its inspections classifications database,
whichnow supports inclusion of facility status based on
classification ofinspection reports from recognised foreign
regulatory authorities. G
Gen 14-9-18 Pgs.1-16.indd 11 11/09/2018 15:55
-
12 GENERICS bulletin 14 September 2018
PRODUCT NEWSBIOLOGICAL DRUGS
Celltrion wants lowerRA criteria in the UKLeading biosimilars
player Celltrion Healthcare has claimed thatthe UK “lags behind
most of Europe” in access to biologics forpatients with rheumatoid
arthritis (RA), as it called for easing ofinitiation boundaries for
biologics that Celltrion says will help thecountry’s National
Health Service (NHS) address access inequality.
“There are set thresholds in disease activity before biologics
canbe used in RA patients, but these thresholds vary across
Europe,”Celltrion explained. According to the Korean firm, the
percentage ofpatients who are treated with tumour necrosis factor
alpha (TNF-α)inhibitors, such as infliximab, is 24% or higher in
countries includingItaly and France, “however, in the UK this drops
to just 15%”.
“This is because in the UK a patient must have a higher DAS-28[a
measure of how severe the disease is] threshold of 5.1 comparedto
only 3.2 in other European countries. Despite the [UK’s]
NationalInstitute for Health and Care Excellence (NICE) widely
acknowledgingthat appropriate biological treatments are clinically
effective for allsub-groups of RA patients, access to these
therapies remains restrictedin the UK on grounds of
cost-effectiveness.”
Celltrion’s Remsima (infliximab) biosimilar of Janssen’s
Remicadebegan rolling out across European markets in early 2015.
Switchingpatients to biosimilar infliximab delivered the NHS
savings of £99.4million (US$127 million) in its most recent
financial year (Genericsbulletin, 10 August 2018, page 13).
As well as the National Rheumatoid Arthritis Society (NRAS)and
the British Society for Rheumatology (BSR), Celltrion
receivedbacking in its plight for NICE to lower the DAS-28 score
from 5.1from Ben Parker, a consultant rheumatologist at
ManchesterUniversity Hospitals.
“We have identified clear disparities in access to biologics
acrossEurope,” noted HoUng Kim, Celltrion Healthcare’s head of
strategyand operations. “With the proven savings gained through the
use ofbiosimilars, this could be a real opportunity for the NHS to
addressthese concerning inequalities.” G
EPILEPSY DRUGS
Oxtellar XR ruling is upheldTWi Pharmaceuticals’ proposed
generic versions of SupernusPharmaceuticals’ Oxtellar XR
(oxcarbazepine) 150mg, 300mgand 600mg extended-release tablets
infringe three patents shieldingthe branded epilepsy treatment, a
US Court of Appeals has ruled,upholding an earlier district court
decision.
New Jersey District Judge Renee Marie Bumb had, in herAugust
2017 decision, also rejected TWI’s assertions that US
patents7,722,898, 7,910,131 and 8,821,930 were invalid, a decision
alsoupheld on appeal (Generics bulletin, 1 September 2017, page
24).
The three patents, of eight listed in the US Food and
DrugAdministration’s (FDA’s) Orange Book, all expire on 13 April
2027.
The decision comes after an appeals court at the end of
2016affirmed a prior district court decision, also handed down by
Bumb,that Actavis infringed certain Oxtellar XR patents
(Genericsbulletin, 6 January 2017, page 19).
Commenting on the TWi appeals court ruling, Supernus saidit
marked “the end of any outstanding litigation issues and
genericchallenges to Oxtellar XR”. G
EDQM – the European Directorate for the Quality of Medicines
–has stopped the distribution of medicines containing valsartan
froma further two Chinese manufacturers, following the detection of
thetoxic impurity N-nitrosodimethylamine (NDMA) in the
activepharmaceutical ingredient (API) that could cause cancer.
HeteroLabs’ and Zhejiang Changming’s certificates of suitability
(CEP)have been suspended by the EDQM, shortly after Zhejiang
Huahaiand Zhejiang Tianyu had theirs suspended (Generics bulletin,
13July 2018, page 1; Generics bulletin, 31 August 2018, page
21).The EDQM has requested that CEP holders with substances that
maypresent a contamination risk investigate and address the
possiblepresence of NDMA, including evaluating manufacturing
processes.Noting it had “been assessing the data received”, the
EDQM said that“it seems that a limited number of sources of
valsartan and otherstructurally-related active substances may
present a risk ofcontamination”. Meanwhile, Health Canada has
updated its list ofvalsartan products that are not recalled,
including to add a Mylanproduct. The agency also noted that “no
additional products havebeen recalled”.
SAMSUNG BIOEPIS has been sued by Genentech in a Delawaredistrict
court for allegedly infringing 21 US patents protecting
theoriginator’s Herceptin (trastuzumab) breast-cancer
treatment.Despite alleging that the firms engaged in the ‘patent
dance’ exchangeof information to assert the patents in suit,
Genentech’s complaintalso contends that Bioepis failed to comply
with its obligationsunder Section 262(l)(2) of the Biologics Price
Competition andInnovation Act (BPCIA) to produce to the firm a
complete copy ofthe abbreviated biologic license application (aBLA)
and additionalmanufacturing process information for its SB3
candidate.
CHILE’S Health Minister Emilio Santelices Cuevas has
reaffirmedthe country’s path to compulsory licences for hepatitis C
drugs,after rejecting an attack by Gilead and an undisclosed
pharmaceuticalassociation on Resolution 399/2018, which sets out
public healthjustifications for the issuing of such licences for
sofosbuvir totreat Chile’s hepatitis C epidemic.
JULPHAR has signed an agreement with Becton, Dickinson
andCompany (BD) to supply disposable insulin pens in the UnitedArab
Emirates (UAE). Through the deal, Julphar’s human
insulinformulations including Jusline R, Jusline N and Jusline
30/70 willbe available for administration through BD’s portfolio of
BD Vystradisposable pens. The same device will be used for insulin
analogues –including insulin glargine and insulin lispro – which
are still underdevelopment. “The disposable insulin pens are now in
the final stagesof the approval process,” Julphar noted, “and are
due to be launched assoon as they have been officially registered
by the Ministry of Health.”
UPSHER-SMITH has launched in the US an AA-rated genericversion
of Lomotil (diphenoxylate/atropine) 2.5mg/0.025mgtablets. Citing
data from Iqvia, Upsher-Smith observed that
thediphenoxylate/atropine tablet market had US sales of
approximatelyUS$64 million for the 12 months ended May 2018.
GERMAN generics players including Sandoz’ 1A Pharma andHexal,
Stada’s Aliud, Teva’s AbZ and Zentiva have securedclearance to
offer olmesartan/amlodipine tablets. Zentiva has alsoobtained
clearance for emtricitabine/tenofovir tablets. Furtherapprovals
have been given to Luye Pharma for fentanyl transdermalplasters,
Glenmark for nortriptyline tablets and salmeterol powderfor
inhalation, Acino for pregabalin capsules and Cipla fortenofovir
tablets. G
IN BRIEF
Gen 14-9-18 Pgs.1-16.indd 12 11/09/2018 15:55
-
13GENERICS bulletin14 September 2018
PRODUCT NEWS
Up to the minute live retail market pricing is available for the
UK and Eireon Wavedata Live at wavedata.net.Alternatively, contact
Charles Joynson at WaveData Limited, UK.Tel: +44 (0)1702 425125.
E-mail: [email protected].
Price WatchIndex
PharmacyProfit Index55.6 63.5
Monthly change -3.3 Monthly change +19.2
August 2018 August 2018
Profits enjoyed by UK independent pharmacists rocketedupwards in
August, according to the latest figures from WaveData,which
reflected a rise of more than a third in pharmacy profits,based on
our representative basket of generics.
As the reimbursement price for the basket jumped by just overan
eighth to £2,252.48 (US$2,902.72) – compared to £1,999.88 inJuly
(Generics bulletin, 3 August 2018, page 12) – the basket priceslid
slightly to £1,183.34 from the previous figure of £1,254.09.This
generated a pharmacy profit value of £1,069.14, comparedto just
£745.79 in July.
Based on Index values of 100 that were set in March 2016,the
Pharmacy Profit Index leapt by 19.2 index points comparedto the
44.3 Index value seen in July, while the Price WatchIndex slid by
3.3 index points to 55.6. G
The Price Watch Index is based on the actual average trade price
according to WaveData of a representativebasket of 20 popular
generic products in March 2016, when the Index was 100. The basket
reflects recentofficial prescribing data for England and Wales and
represents what an average pharmacy would pay forthe products,
which were selected as being the top cash generators within
pharmacy. The Pharmacy ProfitIndex is calculated on the same basis
by applying Drug Tariff reimbursement prices to the basket.
August 2018
PRICE WATCH ....... UK
Basket Price Reimbursement Price Pharmacy Profit£1,183.34
£2,252.48 £1,069.14
RESPIRATORY DRUGS
Glenmark’s Seretideapproved in GermanyGlenmark has edged closer
to launching its first inhalation productin Germany after securing
a local marketing authorisation forits substitutable generic of
GlaxoSmithKline’s Seretide Accuhaler(fluticasone/salmeterol)
dry-powder inhaler.
“There is huge potential for the product in Germany,”
commentedAchin Gupta, executive vice-president and Glenmark’s
business headfor Europe and Latin America. “We are optimistic that
it will helpenhance growth of the European business.”
The Indian firm will sell the generic treatment for asthma
andchronic obstructive pulmonary disease (COPD) in Germany underthe
name Salflutin.
Glenmark’s fluticasone/salmeterol is the result of a
developmentand licensing agreement signed with Polish firm Celon
Pharma in2015, which gave Glenmark semi-exclusive marketing
distributionrights in 15 European markets. As well as Germany,
these includethe UK, Belgium, Italy, the Netherlands and Romania,
along with anumber of Nordic markets.
After successfully closing the decentralised registration
procedurefor the respiratory product in the Nordic region late last
year, Glenmarkhas to date launched the generic inhaler, known as
Salmex in somemarkets, in Denmark, Norway and Sweden, while also
securingmarketing approvals in Finland and Iceland (Generics
bulletin, 25May 2018, page 13). G
BIOLOGICAL DRUGS
Xbrane ‘shifts focus’to biosimilar portfolioXbrane Biopharma has
announced that it is shifting its full strategicfocus to its
biosimilars pipeline in the wake of striking a globalco-development
deal with Stada for its Xlucane (ranibizumab) rival toLucentis. The
strategic shift means that the Swedish firm will abandon,at least
for the time being, development efforts on generic
long-actinginjectables beyond its existing Spherotide (triptorelin)
product.
“As Xbrane’s leading biosimilar Xlucane moves into the
pivotalclinical trial,” the firm observed, “Xbrane is accelerating
developmentof Xcimzane (certoizumab) and Xoncane (pegaspargase) and
willinitiate development of two additional biosimilars on biologics
withpatent expiration in 2026-2028.” As a consequence, it
acknowledged,further development of long-acting injectables beyond
Spherotide“will only be pursued if additional resources become
available”,either “internally or via strategic partnerships”.
“The co-development agreement for Xlucane entered with Stada
inJuly validated the quality and commercial viability of
Xbrane’stechnological platform and capability in biosimilar
development,”the firm insisted (Generics bulletin, 27 July 2018,
page 19). This,combined with the “inherent attractiveness” of
biosimilars, had led thefirm to concentrate on biosimilars and move
away from generic long-acting injectables projects including
risperidone, leuprolide, exenatideand octreotide. “Initially the
development of the biosimilars in thepipeline is done with freed-up
resources from Xlucane development,”the firm said, “However,
long-term successful development requiresthat sufficient capital
can be raised in the market.”
Xcimzane will rival the Cimzia brand, a rheumatoid
arthritis,psoriasis and Crohn’s disease treatment for which the
main patentsare set to expire in 2024 in Europe and the US, Xbrane
noted. Meanwhile,Xoncane’s branded equivalent is the Oncaspar
leukaemia drug.For both biosimilars, Xbrane says it is “leveraging
the company’spatented e.coli-based protein expression technology”,
which offers“significant yield and cost advantage compared to
standard systems”.
“As Xlucane moves into the clinical trial,” said Xbrane
chiefexecutive Martin Åmark, “we are now able to dedicate more
developmentresources to Xcimzane and Xoncane programs. We see very
limitedcompetition and an opportunity to bring the first
biosimilars to market.”
For the two further undisclosed biosimilars, Xbrane said it
would be“expanding its technological platform and capabilities to
the developmentof mammalian cell-based biosimilars”, including
through “strategicpartnerships and a few key recruitments”. Xbrane
once again said it saw anopportunity to be “ahead of the game and
amongst the first to launch”.G
ONCOLOGY DRUGS
Australia approves FulphilaAustralia’s Therapeutic Goods
Administration (TGA) has endorsedMylan’s Fulphila (pegfilgrastim)
biosimilar, according to a listof new approvals published by the
medicines agency. Registeredthrough Mylan’s local Alphapharm
subsidiary, the Fulphila pre-filledsyringes are indicated “for the
treatment of cancer patients followingchemotherapy, to decrease the
duration of severe neutropenia and soreduce the incidence of
infections, as manifested by febrile neutropenia”.
Other TGA approvals included Alphapharm’s atazanavir
capsules,Neo Health’s anagrelide capsules and latanoprost eye
drops, Apotex’eplerenone tablets, and AFT’s pantoprazole powder for
injection. G
Gen 14-9-18 Pgs.1-16.indd 13 11/09/2018 15:55
-
A New ANDA Holder Program Fee Approach Under GDUFA IIFeesThe
ANDA Holder Program fee schedule for Fiscal Year 2019 was just
published by FDA and fees increased by17% from last year. Fees due
to the FDA by October 1, 2018 are as follows:
This is a significant expense for many firms. Those with amodest
number of ANDAs will again be paying substantialsums for drug
products they don’t currently market or that are identified as
Discontinued in the Orange Book. Fora small or medium-tier company
this can be a dramatic hurdle to retain the assets they worked so
hard to own. And,yes, discontinued ANDAs are still considered
approved ANDAs for user fee purposes unless the approval is
withdrawn.
In addition, a one-timemarketing status report was required to
be submitted to the FDA earlier in 2018, identifyingthe submission
as “MARKETING STATUS REPORT / ONE-TIME UPDATE.” While there has
been no guidance asto what happens to the ANDAs identified as “not
marketed”, one scenario may be they will be either movedto
discontinued status or have their approval withdrawn.
PenaltiesWhat is the penalty for not paying the program fee?1)
If the fee is not paid within 20 calendar days after the due date,
the parent company will be placed on a
publicly available arrears list.2) Any ANDA submitted by the
applicant or its affiliateswill not be received.3) All drugs
marketed pursuant to any abbreviated new drug application held by
such applicant or an affiliate
of such applicant shall be deemed misbranded.
A SolutionFor the second year, ANDA Repository, LLC. offers
significant user fee relief and a solution for companies thathave
discontinued ANDAs or drug products not currently marketed. Like
with a parking lot, car owners needspace for their cars, whether in
use or not. Only here, in exchange for the space (and a fee) car
owners transferstitle of the car to the parking lot owner. The
former car owners can, with appropriate notice, resume
ownershipwhen they choose to use the car again. Since the parking
lot owner has enough cars, this venture benefits forall the parties
involved, and the cars remain safe and secure.
In the example above, the car owner is an ANDA owner, and the
parking lot owner is ANDA Repository, LLCwhichcharges ANDA owners
an annual fee that is significantly less than the ANDA Holder Fee
that the FDA charges smallor medium sized firms.
There is NO need to pay excessive fees or be forced to withdraw
your valued assetsdue to short-termmarket conditions, capacity
constraints, API supplier issues, etc.!
Alternatively, if your choice is toWITHDRAWyour ANDAs, wemay be
interested in purchasing them!
URGENT – FY2019 GDUFA Fees JustAnnounced... Increased by 17%
The FY2019 GDUFA Generic Drug Applicant Program Feeis due
October 1st so please contact us soon!
Tier ANDAS Owned FeeSmall 1-5 $186,217Medium 6-19 $744,867Large
20 or more $1,862,167
Phone: +1-570-261-1901 Email: [email protected]
Gen 14-9-18 Pgs.1-16.indd 14 11/09/2018 15:55
-
15GENERICS bulletin
PRODUCT NEWS
AUTOIMMUNE DISEASES TREATMENTS
Remsima broadens accessHikma says it has considerably broadened
access to infliximab inMorocco by introducing its Remsima
biosimilar early last year.The Jordanian firm claims to have helped
increase the size of thelocal market by about 50% to 11,000 vials
per year whilst raisingRemsima’s market share to more than 75%.
“This example demonstrateshow we grow our business and we are not
limited to taking marketshare from the originator,” commented
Hikma’s chief executiveofficer Siggi Olafsson.
Olafsson said Morocco represented about US$3 million of a
totalUS$45 million infliximab market in the Middle East and North
Africa(MENA) region where Hikma has to date launched Remsima in
fiveother countries – Iraq, Jordan, Libya, Saudi Arabia and
Tunisia. By theend of this year, infliximab launches in a further
two MENA marketsare planned under a licensing deal with South
Korea’s Celltrion. G
DERMATOLOGY DRUGS
Oracea ruling leavesAmneal waiting yearsAmneal Pharmaceuticals
has received a mixed verdict in patent-infringement proceedings
with Galderma Laboratories over eightUS patents shielding Oracea
(doxycycline) 40mg capsules. The rulingmeans Amneal is forbidden
from obtaining final abbreviated newdrug application (ANDA)
approval until at least one asserted patentexpires in December
2025.
Delaware District Judge Leonard Stark handed down the rulingto
Amneal, finding that the company’s generic infringed claims offive
patents and did not infringe claims of the remaining three. At
thesame time, Stark batted away an array of invalidity attacks
launchedby the US generics player against certain Oracea patent
claims.
In an 88-page ruling involving eight of the 10 patents listed
inthe FDA’s Orange Book against Oracea, Stark found that
Amneal’sproposed generic product infringed certain claims of US
patents:8,206,740; 8,394,405; 8,470,364; 8,603,506 and 9,241,946.
The ‘946and ‘506 patents expire in April 2022, the ‘405 and ‘364 in
April 2024and the ‘740 patent in December 2025, excluding extension
periods.
On the other hand, Amneal’s product did not infringe US
patents7,749,532, 7,211,267 and 7,232,572. The latter two patents
expire alsoin April 2022, while the ‘532 patent covers the brand
until December 2027.
The patents at-issue were split into two camps: the Chang
patents –‘740, ’405, ’364 and ’532 – and the Ashley patents –’267,
’572, ’506and ‘946. “The Chang and Ashley patents are generally
directed tolow-dose doxycycline formulations for the treatment of
the papulesand pustules of acne rosacea,” the court noted.
According to Stark, Amneal failed to prove “by clear
andconvincing evidence” that the Ashley patents were invalid for
lackof enablement, lack of written description or obviousness.
Individual claims of the ’267, ’506 and ’946 patent were not
invalidas anticipated, Stark also found. Finally asserted claims of
the ‘267and ‘572 patents were not found to be indefinite by
Stark.
Stark’s ruling comes more than three years after the US
PatentTrial and Appeal Board (PTAB) rejected Amneal’s assertions
that the‘740 and ‘405 patents, as well as US patent 8,394,406 that
expires inApril 2024, were not invalid as obvious (Generics
bulletin, 16 January2015, page 18). Amneal currently holds a
tentative approval for itsANDA, alongside Lupin and Mylan. G
ONCOLOGY DRUGS
Alvogen’s gefitinib isapproved in the EUAlvogen says it has
“successfully concluded multiple registrationapplications” in the
European Union (EU) for generic alternativesto AstraZeneca’s Iressa
(gefitinib) 250mg tablets. Having fully developedthe lung-cancer
therapy in-house through its Taiwanese affiliate,
LotusPharmaceuticals, Alvogen and its partners have filed for
marketingauthorisations in 24 European countries.
Citing Iqvia data showing that European sales of Iressa
totalledUS$136 million last year, Alvogen claims it is “among the
firstcompanies in Europe to obtain approval” for a bioequivalent
versionof the treatment for non-small cell lung cancer.
Mylan recently secured a positive opinion from the committeefor
human medicinal products (CHMP) within the European MedicinesAgency
(EMA) for its gefitinib 250mg tablets (Generics bulletin,3 August
2018, page 17). The register of decentralised and
mutual-recognition approvals maintained by EU Heads of Medicines
Agencies(HMA) shows gefitinib authorisations for companies
including DrReddy’s Betapharm, Doc Generici, Krka, Sandoz, Stada
and Synthon.
AstraZeneca enjoys supplementary protection certificate
(SPC)protection for Iressa until early March next year. Those SPCs
arebased on European patent EP0,823,900, which expired in April
2016,and a first marketing authorisation in Liechtenstein that was
grantedin March 2004, 15 years before the SPCs expire, on the basis
of legalarrangements with Switzerland’s Swissmedic agency.
In the UK, AstraZeneca challenged the local SPC expiry date of1
March 2019 and argued instead that the SPC should run until 22April
2021, based on the first marketing authorisation having beenan EU
approval for Iressa granted in 2009. The UK referred the issueto
the Court of Justice for the EU (CJEU), which in November
2013determined that “an administrative authorisation issued for a
medicinalproduct by Swissmedic, which is automatically recognised
in Liechtenstein,must be regarded as the first authorisation to
place that medicinalproduct on the market” (Generics bulletin, 6
December 2013, page 17).G
ANTIDEPRESSANTS
Ranbaxy dodges bupropion barSun Pharma’s Ranbaxy has avoided a
legal bar on obtaining Canadianapproval for its generic Wellbutrin
XL (bupropion) 150mg and300mg extended-release tablets. Federal
Court Judge Glennys McVeighfound that Ranbaxy’s formulation of the
antidepressant did not infringeValeant’s Canadian patent 2,524,300,
which expires on 8 August 2023.Immediately after the ruling was
delivered, Health Canada approvedRanbaxy’s generics.
Noting that Ranbaxy had not challenged the validity of the
‘300formulation patent, McVeigh said the dispute centred on whether
thegenerics firm’s tablets fell within the scope of the ‘300
patent’s soleindependent claim by containing a permeation enhancer
in an amountof “about 20% to about 40% of the moisture barrier dry
weight”.
On claim construction, McVeigh construed both
‘permeationenhancer’ and ‘about 20% to about 40% of the moisture
barrier dryweight’ to be essential elements in the ‘300 patent, and
said that‘about’ indicated a variance of up to 10%, giving an
effective rangeof 18% to 44%. As silicon dioxide, the only
permeation enhancerin Ranbaxy’s formulation, fell outside of that
range, the generic didnot infringe, McVeigh ruled. G
Gen 14-9-18 Pgs.1-16.indd 15 11/09/2018 15:55
-
16 GENERICS bulletin 7 September 2018
PEOPLE
Register online: www.europlx.com
The Original since 1995.Often copied. Never equaled.
Seeking and offering business opportunities in patented and
generic (incl.biosimilars), prescription and OTC drugs, medical
devices, and nutraceuticals -development, licensing, marketing,
promotion, and distribution…
Each euroPLX Conference’s actual collaboration interests are
summarised anddisplayed onwww.europlx.com as an hourly updated
Dynamic PartneringFocus, as soon as sufficient data are submitted
by registrants.
[email protected]. ++49 (6221) 426296-0
Insanely EffectivePharma PartneringeuroPLX is the world’s most
often heldpartnering conference for the pharmaand biopharma
industries.Because of results delivered. Year-round.
Join the 68th International PartneringConference for Pharma
Business Development
euroPLX 68 Athens (Greece)November 26 + 27, 2018, Hotel Grande
Bretagne, Athens
APPOINTMENTS
Dierks follows Walzas NuPharm’s chiefNuPharm has appointed
former Meda chief executive officer (CEO)Jörg-Thomas Dierks to
become CEO of the European centralnervous system (CNS) specialist,
replacing with immediate effectStephan Walz, who has “decided to
step down in order to pursueother activities”.
Boasting “30 years of healthcare experience”, Dierks has
heldpositions including chief operating officer and chief
scientific officerof Meda, as well as CEO – leading up to the
company being boughtby Mylan in 2016 (Generics bulletin, 26 August
2016, page 3) – aswell as chief operating officer of Germany’s
Viatris.
NuPharm was created in 2016 by combining five companies –Spain’s
Qualigen, Laboratorios Lesvi and Inke; Germany’s Neuraxpharm,which
also operates in Poland; and Italy’s FB Health – with
investmentgroup Apax Partners. It recently completed a deal to add
France’sBiodim for an undisclosed sum (Generics bulletin, 13 July
2018,page 3). “I am delighted to be joining NuPharm at an
excitingtime,” Dierks commented.
Noting that the company “has successfully created a
Europeanplatform of scale and become a key player in the treatment
of CNSdiseases”, Dierks said he would work with the management team
to“build on the positive developments that have been made and lead
thecompany through its next phase of growth, with the objective to
makeit a prominent European player in the CNS field”. G
APPOINTMENTS
Albrecht hands overStada to GoldschmidtFormer Sandoz US
president Peter Goldschmidt has taken overas chief executive
officer of Stada, taking the reins from ClaudioAlbrecht. The
“professional and amicable” handover is in line withsuccession
plans announced by the German company early this year(Generics
bulletin, 9 February 2018, page 1). According to Stada,Goldschmidt
will use the first 100 days of his tenure to “intensivelyget to
know the group, its partners, and its customers, and will
thendiscuss his strategic priorities with his team”.
“I look forward to working with the highly experienced team
atStada to continue the group’s long-term growth,” Goldschmidt
said.“I have known Stada as a key player in the industry for many
years, andI see enormous potential for the group. Together with all
employeeswe will strive to fully capitalise on the opportunities
for growth.”
Goldschmidt said he was “in complete alignment with our
majorityowners, Cinven and Bain Capital” – which took control of
Stada lastyear and appointed Albrecht as chief executive (Generics
bulletin,8 September 2017, page 1) – “on their strategy for
building a companywith long-term growth potential”. “Our focus
remains on continuingto market a competitive portfolio and working
closely with our globalnetwork of strategic partners.”
Under German ‘cooling-off’ regulations, Albrecht will not take
aseat on Stada’s supervisory board, but will return to his
AlbrechtProck & Partners consultancy business. G
Gen 14-9-18 Pgs.1-16.indd 16 11/09/2018 15:55