Jens Heisterberg - Patient involvement in drug development and licensing

Patient involvement in drug development and

licensingBenefits, challenges and pitfalls

Jens HeisterbergVP Regulatory Intelligence

Novo Nordisk A/S

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Patient Involvement SeminarCopenhagen, 2 March 2017

• Physician, clinical pharmacologist

• Since June 2016 at Regulatory Intelligence, Novo Nordisk A/S

• Chief medical officer at the Danish Medicines Agency 2010 - May 2016

• Danish CHMP member for about 6 years

• Know the EU regulatory system well

• Some, but limited knowledge about the US regulatory system

My background

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• Transparency• Clearly define purpose and scope of interaction• Obtain written informed consent by patients

• Independence• Treat patients as equal partners• Respect and encourage different opinions• Ensure that patients are free to collaborate with other companies or organisations

• Arm’s length principle• Contact patients only through patient organisations, market research agencies or

other third parties• Never base interactions on the condition that patients will use the company’s products• Never promote or advertise products• Never discuss or undermine competitor products• Never discuss patient-specific or treatment-specific issues

• Fees• Pay compensation fee for work time lost rather than salary• Comply with local legal regulations

When companies engage with patients…

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• Medical doctors knew the interests of their patients

• Experts could speak on behalf of the patients

• There was no need to ask the patients

The “good” old days…

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• Patient input to identification of unmet medical need

• Patient input to design of clinical trials

• Patient review of information material

• Patient reported outcomes in clinical trials

• Patient engagement in evaluation of benefit-risk balance

• Patient participation in licensing decisions

What could patient involvement in drug development and licensing entail? Examples

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• Patient input to identification of unmet medical need

• Patient input to design of clinical trials

• Patient review of information material

• Patient reported outcomes in clinical trials

• Patient engagement in evaluation of benefit-risk balance

• Patient participation in licensing decisions

Focus of this presentation

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Licensing medicines in the EU: Four procedures

• National

• Mutual recognition (MRP)

• Decentralised (DCP)

• Centralised

The centralised procedureMandatory for some medicines

• Biologics

• Advanced therapies

• Medicines for certain diseases• AIDS

• Cancer

• Neurodegenerative disorders

• Diabetes

• Auto-immune diseases

• Viral diseases

• Orphan medicines

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The centralised procedure

• Legally binding in the entire EU/EEA

• Scientific assessment performed by the Committee for Medicinal Products for Human Use (CHMP) under EMA

• Marketing authorised issued by the European Commission

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CHMP

• Committee for Medicinal Products for Human Use

• Makes recommendations to the EU Commission• The centralised procedure

• Arbitration cases (when member states cannot reach agreement in other licensing procedures)

• Members• One member and one alternate member from each member state

• Five co-opted members representing a specific expertise (biotechnology, quality, paediatrics, biostatistics…)

• Monthly 4-day meeting at EMA

• Decisions made by simple majority

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Assessment process

• Two Rapporteur teams are appointed – each from one member state• Assessor teams consist of:

• Quality assessors• Non-clinical assessors• Clinical team

• Efficacy• Safety and tolerability• Risk management plan

• 210-day procedure plus clock stops• Other member states provide comments during the procedure• Often interactions with the FDA• The CHMP adopts questions which are then forwarded to the applicant

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There is a lot of hype and buzz…

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Patient-focussed

• To get more efficacious and safer medicines on the market

• Patients are experts on their own disease and may qualify benefit-risk evaluations

• Unknown if that is the case (some evidence, but difficult to test conclusively)

• To address a democratic gap

• Patients are the ones experiencing the side effects as well as the benefits of new medicines

• As the end-user and ultimate stakeholder, one may argue that patients have a democratic right to be involved in the licensing process

But why at all involve patients in the licensing process? Top-level perspective

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It all started in the eighties and the nineties

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Extracts from:Cassy Boff. History of AIDS Activism (2006). www.tcnj.edu

Milestones of EMA interactions with patients and consumers

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From: EMA website, accessed 16Feb2017

Number of patient and consumer involvement in EMA activities increasing significantly

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From: European Medicines Agency’s interaction with patients, consumers, healthcare professionals and their organisations. Annual report 2015

Patients/consumers in EMA activities

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From: European Medicines Agency’s interaction with patients, consumers, healthcare professionals and their organisations. Annual report 2015.

Committee Patient representation Remark

CHMP Pilot ongoing: Patients involved in CHMP discussions in selected cases when CHMP is undecided and there is an unmet medical need

PRAC 1 member and 1 alternate

COMP 3 members

HMPC

CAT 2 members and 2 alternates

PDCO 3 members and 3 alternates

Which EMA committees have patient representation?

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Body Patient representation

Remark

Patients' and Consumers' Working Party

Other working parties For some working parties, patients representatives may be consulted

Scientific Advisory Groups

Patient representatives often consulted and part of meetings

Which EMA Working Parties/Scientific Advisory Groups have patient representation?

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Patient and consumer involvement in EMA activities

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From: European Medicines Agency’s interaction with patients, consumers, healthcare professionals and their organisations. Annual report 2015.

• Presence of patient representatives often changes the dynamics of a meeting with regulators and experts

• Best when specific, user-focussed input is provided

• Perspective on efficacy compared to already established therapy

• Clinical significance of side effects in the context of efficacy results

• Aspects on practical use

• Advantage if patient representative is familiar with the specific situation of the patients targeted with the medicine in question

Personal experience with patient involvement in the drug licensing process

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• General input on seriousness of disease and unmet medical need has been less helpful

• Regulators become uncomfortable when things get emotional

• Most patient representatives make a true effort to represent the views of their fellow patients and not just themselves

• However, some representatives pursue “hobby horses” of their own

• Sometimes patients are less risk-aversive than regulators, sometimes not

Personal experience with patient involvement in the drug licensing process

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• Potential conflicts of interest

• It can be an intimidating experience for patients to sit with regulators and experts

• Need for thorough preparations, mentors…

• Practical issues (access in case of mobility challenges, special food requirements…)

• Good English language skills often mandatory

Challenges with patient involvement in the drug licensing process

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• This is a possibility

• For example, a company is entitled to an oral explanation if facing a negative opinion at the end of the licensing procedure

• …and patients (or relatives) can be part of the company delegation

• Requires careful considerations by the company

• Essential that the patients are free to speak their mind and do not appear choreographed to present company positions

When companies bring their own patients in front of regulators…

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• Many examples where patients have provided valuable input to the evaluation of benefits and risks of new medicines and qualified the decision-making

• Several aspects to take into consideration when bringing patients together with regulators

• Patient involvement in the licensing process still in its infancy

• How to best structure/organise patient involvement? Which committees?

• Voting/decision power?

Conclusion

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