This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands
An agency of the European Union
Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000
Descovy Procedural steps taken and scientific information after the authorisation
Application
number
Scope Opinion/
Notification1
issued on
Commission
Decision
Issued2 /
amended
on
Product
Information
affected3
Summary
IAIN/0047/G This was an application for a group of variations. B.II.e.5.a.1 - Change in pack size of the finished
product - Change in the number of units (e.g.
tablets, ampoules, etc.) in a pack - Change within
the range of the currently approved pack sizes B.II.e.5.a.1 - Change in pack size of the finished
product - Change in the number of units (e.g.
tablets, ampoules, etc.) in a pack - Change within
13/03/2020 SmPC,
Labelling and
PL
1 Notifications are issued for type I variations and Article 61(3) notifications (unless part of a group including a type II variation or extension application or a worksharing application). Opinions are issued for all other procedures. 2 A Commission decision (CD) is issued for procedures that affect the terms of the marketing authorisation (e.g. summary of product characteristics, annex II, labelling, package leaflet). The CD is issued within two months of the opinion for variations falling under the scope of Article 23.1a(a) of Regulation (EU) No. 712/2012, or within one year for other procedures. 3 SmPC (Summary of Product Characteristics), Annex II, Labelling, PL (Package Leaflet).
EMA/194924/2020 Page 2/22
the range of the currently approved pack sizes
II/0044 C.I.13 - Other variations not specifically covered
elsewhere in this Annex which involve the submission
of studies to the competent authority
27/02/2020 n/a
WS/1746 This was an application for a variation following a
worksharing procedure according to Article 20 of
Commission Regulation (EC) No 1234/2008. B.I.d.1.a.4 - Stability of AS - Change in the re-test
period/storage period - Extension or introduction of a
re-test period/storage period supported by real time
data
06/02/2020 n/a
PSUSA/10515
/201904
Periodic Safety Update EU Single assessment -
emtricitabine / tenofovir alafenamide
31/10/2019 n/a PRAC Recommendation - maintenance
IG/1125 B.II.b.1.a - Replacement or addition of a
manufacturing site for the FP - Secondary packaging
site
25/06/2019 n/a
WS/1429 This was an application for a variation following a
worksharing procedure according to Article 20 of
Commission Regulation (EC) No 1234/2008. Update of sections 4.2, 4.4, 4.8, 5.1 and 5.2 of the
SmPC of Descovy, Genvoya and Odefsey with data in
patients on chronic haemodialysis from the Study
GS-US-292-1825; this is a Phase 3b Open-Label
Study to Evaluate the Safety, Tolerability,
Pharmacokinetics and Efficacy of E/C/F/TAF Fixed
26/04/2019 06/06/2019 SmPC,
Labelling and
PL
In study GS US 292 1825, the efficacy and safety of of
emtricitabine + tenofovir alafenamide in combination with
elvitegravir + cobicistat as a fixed-dose combination tablet
in HIV-1 infected adults with end stage renal disease
(estimated CrCl < 15 mL/min) on chronic haemodialysis
were evaluated. There were no new safety issues identified
in these patients. No clinically relevant differences in
tenofovir alafenamide pharmacokinetics were observed in
patients with end stage renal disease on chronic
haemodialysis as compared to those with normal renal
EMA/194924/2020 Page 3/22
Dose Combination (FDC) in HIV-1 Infected Subjects
on Chronic Haemodialysis. The Package Leaflet is
updated accordingly. In addition, the Worksharing applicant (WSA) took
the opportunity to remove boceprevir drug-drug
interaction information in section 4.5 of the SmPC
since this medicinal product has been withdrawn
from the EU market, as well as to introduce some
minor amendments throughout the product
information of Descovy, Genvoya and Odefsey. The
Package Leaflet is updated accordingly. Moreover, the Package Leaflet of Genvoya and
Odefsey have been updated regarding the lactose
wording, as per the revised Annex to the European
Commission guideline on ‘Excipients in the labelling
and package leaflet of medicinal products for human
use’; as well as an administrative correction to the
Genvoya Package Leaflet in order to add “lurasidone”
to the second list of contra-indicated drugs. C.I.4 - Change(s) in the SPC, Labelling or PL due to
new quality, preclinical, clinical or pharmacovigilance
data
function. Efficacy was maintained through 48 weeks but
emtricitabine exposure was significantly higher than in
patients with normal renal function. Although there were no
new safety issues identified, the implications of increased
emtricitabine exposure remain uncertain. Therefore, it is recommended that Descovy, Genvoya and
Odefsey should generally be avoided but may be used in
adults with end stage renal disease (estimated CrCl < 15
mL/min) on chronic haemodialysis if the potential benefits
are considered to outweigh the potential risks. No dose
adjustment is required in these patients. Based on this,
sections 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC of Descovy,
Genvoya and Odefsey have been updated accordingly.
WS/1566 This was an application for a variation following a
worksharing procedure according to Article 20 of
Commission Regulation (EC) No 1234/2008. Update of section 4.8 of the SmPC following a safety
review by the MAH assessing the clinical evidence of
02/05/2019 SmPC, Annex
II, Labelling
and PL
Based on post-marketing surveillance data, there is
sufficient evidence to consider that a causal association
between tenofovir alafenamide-containing products and two
adverse events, angioedema and urticaria, with the
frequency uncommon. The Product information is updated
EMA/194924/2020 Page 4/22
a causal association between tenofovir alafenamide-
containing products and two adverse events,
angioedema and urticaria. The Package Leaflet is
updated accordingly. In addition, the MAH took the
opportunity to implement minor linguistic
amendments and editorial changes to the Odefsey
and Vemlidy products information. C.I.4 - Change(s) in the SPC, Labelling or PL due to
new quality, preclinical, clinical or pharmacovigilance
data
accordingly.
IG/1009 B.I.b.1.d - Change in the specification parameters
and/or limits of an AS, starting
material/intermediate/reagent - Deletion of a non-
significant specification parameter (e.g. deletion of
an obsolete parameter)
18/12/2018 n/a
WS/1466/G This was an application for a group of variations
following a worksharing procedure according to
Article 20 of Commission Regulation (EC) No
1234/2008. A.4 - Administrative change - Change in the name
and/or address of a manufacturer or an ASMF holder
or supplier of the AS, starting material, reagent or
intermediate used in the manufacture of the AS or
manufacturer of a novel excipient B.I.a.1.z - Change in the manufacturer of AS or of a
starting material/reagent/intermediate for AS - Other
variation B.I.a.1.f - Change in the manufacturer of AS or of a
29/11/2018 n/a
EMA/194924/2020 Page 5/22
starting material/reagent/intermediate for AS -
Changes to quality control testing arrangements for
the AS -replacement or addition of a site where
batch control/testing takes place
IG/1001 B.I.b.1.d - Change in the specification parameters
and/or limits of an AS, starting
material/intermediate/reagent - Deletion of a non-
significant specification parameter (e.g. deletion of
an obsolete parameter)
23/11/2018 n/a
PSUSA/10515
/201804
Periodic Safety Update EU Single assessment -
emtricitabine / tenofovir alafenamide
31/10/2018 n/a PRAC Recommendation - maintenance
IA/0038 B.II.b.3.a - Change in the manufacturing process of
the finished or intermediate product - Minor change
in the manufacturing process
25/10/2018 n/a
WS/1441 This was an application for a variation following a
worksharing procedure according to Article 20 of
Commission Regulation (EC) No 1234/2008. C.I.11.b - Introduction of, or change(s) to, the
obligations and conditions of a marketing
authorisation, including the RMP - Implementation of
change(s) which require to be further substantiated
by new additional data to be submitted by the MAH
where significant assessment is required
04/10/2018 n/a
WS/1430 This was an application for a variation following a
worksharing procedure according to Article 20 of
Commission Regulation (EC) No 1234/2008.
04/10/2018 n/a
EMA/194924/2020 Page 6/22
B.I.d.1.z - Stability of AS - Change in the re-test
period/storage period or storage conditions - Other
variation
IG/0983 C.I.z - Changes (Safety/Efficacy) of Human and
Veterinary Medicinal Products - Other variation
13/09/2018 06/06/2019 SmPC
IAIN/0037 B.II.b.1.b - Replacement or addition of a
manufacturing site for the FP - Primary packaging
site
11/09/2018 n/a
T/0030 Transfer of Marketing Authorisation
25/04/2018 28/05/2018 SmPC,
Labelling and
PL
IB/0029 C.I.11.z - Introduction of, or change(s) to, the
obligations and conditions of a marketing
authorisation, including the RMP - Other variation
16/04/2018 n/a
PSUSA/10515
/201710
Periodic Safety Update EU Single assessment -
emtricitabine / tenofovir alafenamide
12/04/2018 n/a PRAC Recommendation - maintenance
WS/1310 This was an application for a variation following a
worksharing procedure according to Article 20 of
Commission Regulation (EC) No 1234/2008. Update of section 4.5 of the Descovy, Genvoya,
Odefsey and Vemlidy SmPCs in order to include
information on the drug-drug interaction with
sofosbuvir/velpatasvir/voxilaprevir fixed dose
combination based on the results of study GS-
22/03/2018 28/05/2018 SmPC
EMA/194924/2020 Page 7/22
US0367-1657, listed as a category 3 in the Vemlidy
RMP, in order to fulfil MEA 006 for Vemlidy. Study
GS-US0367 is a phase I multiple dose study to
evaluate the drug-drug interaction potential between
sofosbuvir/velpatasvir/voxilaprevir fixed dose
combination and HIV anti-retrovirals in healthy
subjects. In addition, the Worksharing applicant (WSA) took
the opportunity to make some small corrections to
section 4.5 of the SmPC for Descovy, Genvoya,
Odefsey and Vemlidy and to make corrections to the
DE, ES, HU, IS, IT, LV, NO, PT, SL and SV
translations for Vemlidy. C.I.4 - Change(s) in the SPC, Labelling or PL due to
new quality, preclinical, clinical or pharmacovigilance
data
II/0025 Update of sections 4.8, 5.1 and 5.2 of the SmPC in
order to reflect week 48 results from study GS-US-
311-1717, listed as a category 3 study in the RMP;
this is a Phase 3b, randomized, double-blind, switch
study to evaluate Descovy (F/TAF) in HIV-1 infected
subjects who are virologically suppressed on
regimens containing abacavir/lamivudine (ABC/3TC). In addition, the Marketing authorisation holder
(MAH) took the opportunity to make administrative
updates and Minor Linguistic Amendments to the
Product Information. C.I.4 - Change(s) in the SPC, Labelling or PL due to
18/01/2018 19/04/2018 SmPC
EMA/194924/2020 Page 8/22
new quality, preclinical, clinical or pharmacovigilance
data
WS/1305 This was an application for a variation following a
worksharing procedure according to Article 20 of
Commission Regulation (EC) No 1234/2008. B.I.a.1.z - Change in the manufacturer of AS or of a
starting material/reagent/intermediate for AS - Other
variation
18/01/2018 n/a
IG/0877 A.4 - Administrative change - Change in the name
and/or address of a manufacturer or an ASMF holder
or supplier of the AS, starting material, reagent or
intermediate used in the manufacture of the AS or
manufacturer of a novel excipient
21/12/2017 n/a
IG/0861 B.I.a.3.a - Change in batch size (including batch size
ranges) of AS or intermediate - Up to 10-fold
increase compared to the originally approved batch
size
17/11/2017 n/a
PSUSA/10515
/201704
Periodic Safety Update EU Single assessment -
emtricitabine / tenofovir alafenamide
26/10/2017 n/a PRAC Recommendation - maintenance
IA/0022 B.II.b.3.a - Change in the manufacturing process of
the finished or intermediate product - Minor change
in the manufacturing process
17/10/2017 n/a
WS/1205 This was an application for a variation following a
worksharing procedure according to Article 20 of
Commission Regulation (EC) No 1234/2008.
14/09/2017 19/04/2018 SmPC Based on data from the in vitro study AD-120-2045, co
administration of tenofovir alafenamide and xanthine
oxidase inhibitors (e.g. febuxostat) is not expected to
EMA/194924/2020 Page 9/22
Update of section 4.5 of the SmPC of Genvoya,
Descovy and Odefsey in order to provide the final
study report for the in vitro study AD-120-2045; this
is a non-clinical study on the Effect of Xanthine
Oxidase Inhibitors on Metabolism of Tenofovir
alafenamide fumarate in Primary Human
Hepatocytes. This study is listed in the respective Risk
Management Plans as an additional
pharmacovigilance activity (Category 3) (Genvoya:
MEA 006; Descovy: MEA 004; Odefsey: MEA 007). C.I.4 - Change(s) in the SPC, Labelling or PL due to
new quality, preclinical, clinical or pharmacovigilance
data
increase systemic exposure to tenofovir in vivo.
IB/0021 B.II.f.1.b.1 - Stability of FP - Extension of the shelf
life of the finished product - As packaged for sale
(supported by real time data)
05/09/2017 19/04/2018 SmPC
IG/0799 B.I.a.1.f - Change in the manufacturer of AS or of a
starting material/reagent/intermediate for AS -
Changes to quality control testing arrangements for
the AS -replacement or addition of a site where
batch control/testing takes place
14/07/2017 n/a
WS/1136 This was an application for a variation following a
worksharing procedure according to Article 20 of
Commission Regulation (EC) No 1234/2008. Update of sections 4.4, 4.8, and 5.1 of the SmPC in
06/07/2017 19/04/2018 SmPC and PL The following existing information in the SmPC was