Month: novembre 2017

Gene therapy: the trap of biomanufacturing

With the recent approval of Yescarta and Kymriah CAR-T therapies in the US market, several years after approval of Glybera and Strimvelis in Europe, the therapeutic proof of concept of gene therapy has been validated. The next, though highly challenging, step for gene therapy development will be to bypass current limitations of biomanufacturing technologies.

The principle of gene therapy is to bring functional DNA to a patient suffering genetic disease. The current trend, for both ex vivo and in vivo treatments, is the use of viruses for delivering the repaired DNA to patient cell. Manufacturing these vectors is a technical and financial bottleneck for current gene therapy development.

Ex vivo gene therapy is the first stage of innovative biomanufacturing

Yescarta (Gilead) and Kymriah (Novartis) have been approved in 2017 in the US1,2. Both treatments are intended to treat rare cancers and are based on CAR-T technology: a genetic modification of immune cells to make them attack the tumour of the patient. In Europe, Strimvelis (GSK) was approved at the end of 2016 for the treatment of Severe Combined Immunodeficiency due to Adenosine Deaminase deficiency (ADA-SCID) by modification of patient hematopoietic stem cells. All these treatments consist of an ex vivo modification of autologous (from the patient himself) cells to give their function back or provide a new function.

Manufacturing processes of these therapies have been validated but are long and complex: they require cell extraction and modification (with DNA loaded viruses) before reintroducing the cell to the patient. Thus, Strimvelis process is only carried out at MolMed and San Raffaele Hospital (Milan Italy), where it has been developed, and patients must travel there to get treated – cryopreservation of modified cells is not set yet.

Ex vivo therapies need smaller amount of viruses compared to in vivo therapies. This is one of the main reasons why they reached the market first.

Several other ex vivo treatments, developed by American firms, such as BlueBird Bio with Lenti-D (for the treatment of cerebral adrenoleukodystrophy) and LentiGlobin (for the treatment of transfusion-dependant B-Thalassemia) and European biotech, such as Orchard Therapeutics (OTL-101 for ADA-SCID) are expected to reach the market soon. Biomanufacturing is already prepared for these products; BlueBird Bio set a supply agreement with Lonza in the US and Apceth in Europe, whilst Orchard partnered with PharmaCell.

In vivo gene therapy faces the technical and financial challenges of targeting large organs

Glybera was the first in vivo gene therapy approved in Europe in 2012, for lipoprotein lipase deficiency. It was withdrawn for profitability reasons, with only one treatment sold since its approval in 2012. Uniqure sold Glybera for a fee in excess of 1m€. The price was high partly due to high R&D and manufacturing costs, driven by production of loaded viruses (dose around 1012 vg/kg).

In vivo gene therapy is mostly based on DNA loaded adeno associated viruses and requires higher doses of viruses because of the lower rate of transfection compared to ex vivo. Furthermore, viruses must reach the right tissue after in vivo injection. For these reasons, most of the approved-to-date gene therapies are ex vivo and most mature in vivo therapies are focussing on easy-to-reach small organs. Examples include Spark therapeutics’ Luxturna or Gensight’s GS010 product, which are both intended for ophthalmic disease.

Luxturna is in the process of approval in the US and Europe, and focusses on Leber congenital amaurosis and retinitis pigmentosa diseases. Its administration requires a dose around 1012vg/kg, to target eyes.

To target larger organs such as the liver, CNS or skeletal muscles, the required dose of viruses must be increased. AveXis, for Spinal Muscular atrophy, expects the clinical trial dosage to be around 1014vg/kg3, a hundred time higher than Glybera and Luxturna. AveXis took the strategic decision to control their manufacturing activity by having in-house capabilities and developing future marketable processes. In September, this process received FDA authorization for use in next trials.

On a technical prospective, most of the actual AAV production processes are based on sub-optimal transient transfection of mammalian cells, which requires expensive plasmids and transfection agents in large quantities. Other approaches are under development, such as stable cell lines and baculovirus-mediated production, to answer the demand of large volumes when reaching clinical or commercial stage4. Even if the recent move from adherence culture to suspension bioreactors was an improvement, each step of the product manufacturing needs to be optimized to improve yields, starting from the type of vector used.

Pharmaceutical companies and CMOs have increased interest for gene therapy biomanufacturing

Pharmaceutical industries have started investing in gene therapy manufacturing capacities. In 2016, Pfizer demonstrated strategic importance of gene therapy manufacturing technologies: they acquired Bamboo therapeutics, which had become famous for the discovery of a more yield-efficient mammalian cell line.

Owning biomanufacturing forces in US and Europe is essential to provide treatments to patients in both locations. The European pharmaceutical group Merck (EMD Serono) invested in gene therapy manufacturing plants in the UK and the US (BioReliance), strategically combining positions in North America and Europe for supplying therapies to patients on both continents.

Their plants, like many of the gene therapy manufacturing entities, offer CMO services. Gene therapy CMOs are not traditional manufacturers, as they also innovate production processes, to ascertain an easy-to-scale, affordable technique. Following the US, firms across Europe including Oxford BioMedica, YposKesi, Lonza, UniQure, Cell for Cure, etc… are developing and strengthening capabilities in gene therapy biomanufacturing. Europe will position as a competitive player in gene therapy.

Biomanufacturing will remain the challenge of gene therapy development in the next year, especially regarding viral production. Recent development of CRISPR-Cas9 editing therapy, may even enhance this trend, as virus may be the answer to treatment delivery.

1 – Press release – “Kite’s Yescarta becomes first CAR-T therapy approved by the FDA for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy” – oct 2017
2 – Press release – “Novartis receives first ever FDA approval for a CAR-T cell therapy, Kymriah™ (CTL019), for children and young adults with B-cell ALL that is refractory or has relapsed at least twice” – aug 2017
3 – Press release – “AveXis announces plan to initiate pivotal trial of AVXS-101 in SMA type 1 using product from new GMP commercial process” – sept 2017
4 – Tony Hitchcock “manufacturing of AAV vectors for gene therapy” – jul 2017

How will Brexit affect the strategies of US biotechs already in the UK, in Europe, or about to cross the Atlantic?

Dwight D. Eisenhower and Charles de Gaulle didn’t necessarily see eye to eye on many things, but both understood the strategic advantage the UK could provide to the US to set foot in Europe.

What was true from a military or political standpoint in the XXth century was still very relevant from a business point of view in the XXIst century until, on June 23rd, 2016, the UK electorate voted in favour of leaving the European Union, or in short, Brexit. As per the timelines of article 50 of the Lisbon Treaty, describing the procedure to exit the EU, Brexit will become effective on March 29th, 2019.

Current state UK for US biotechs

For the time being, the UK offers a quite favourable environment for US biotech’s: a large English-speaking population (65M+ inhabitants) with access to a performant healthcare system (NHS budget of ~170B€ in 2015-2016 [1]), supported by the lowest Corporate Tax in the G20 (20% [2]) and generous tax deductions on work related to R&D (SME may get up to 230% of R&D expenditure in deduction from their profit [3]). Furthermore, it provides access to the Single Market: 500+ Million people with a 14 Trillion €GDP [4] ($16 Trillion).

The risks and uncertainties that come with Brexit

While Brexit will impact all interactions between the UK and EU, from innovation and its funding to trade and tariffs, four areas of particular relevance for US biotechs will be covered here.

Innovation at risk

The UK is currently the main beneficiary from the European Research Council grants [5], with most projects involving intra-European collaboration [6]. Exiting EU with no deal to maintain participation to European funding would certainly hinder academic research. Interestingly, it would harm also R&D in the private sector, as there is a positive correlation between government and private R&D spending [7]: a poorly negotiated Brexit would reduce the attractiveness of the UK R&D ecosystem.

R&D occurs where ideas, money and talented people meet. The UK currently provides access to high-quality infrastructure, and world-class educational institutes that attract current and future leading scientists: about 16% of STEM academics are non-UK EU nationals [8], and their employment or even stay could be at risk upon Brexit.

Such factors may ultimately impact the decision on where firms will establish their research centres.

Fewer, costlier Clinical Trials

The UK is consistently in the top three countries in Europe for the number of clinical trials in Phase I, II or III and this premium spot could be threatened as the UK leaves the EU: to simplify management and increase efficiency & transparency of clinical trials across Europe, the European Commission has designed the Clinical Trial Regulation (EU No. 536/2014 [9]). As the UK pulls out of the EU, it might be easier for companies to set up clinical trials across Europe and leaving the UK aside.

Trickier Intellectual property protection

The EU is trying to simplify IP protection with unified patents and a unified patent court imposing jurisdiction in all EU member countries (Unified Patent Court Agreement (16351/12) and regulations 1257/2012 and 1260/2012 [10]). Being outside of the EU, the UK would not fall under this court jurisdiction. Whilst the UK may offer easy and quick access for local patent submission, the work to get IP protection in both the UK and EU would still need to be duplicated.

Delays in Drug Approval

At the moment, CE marking for medical device offers marketability across EU, and European Commission marketing authorization, after EMA evaluation, is valid in all countries in the European Economic Area (EEA), which is currently comprised of 28 EU countries, including the UK, plus Norway, Lichtenstein, and Iceland. Approval could become more complex and be delayed depending on the outcome of the ongoing negotiations.

Possible negotiation outcomes

After the June 23rd vote, Theresa May became the new prime Minister and the British Government invoked article 50 of the Lisbon Treaty on the European Union on March 29th, 2017, setting the UK on a course to leave the EU on March 29th, 2019. Since then, negotiations have been afoot and three possible scenarios have been discussed:

EEA membership (like Norway, Lichtenstein, Iceland)

• Enforce the “four freedoms”: Free movement of persons, goods, services and capital within the European Single Market (ESM).
• Contribute financially to access the ESM and to support other EU programs (eg ~800M€ for Norway in 2016 [11]).
• Implement most EU legislations including Marketing Authorization after EMA evaluation, and free marketability of CE labelled medical devices – excluding agriculture and fisheries.

 

This would be the solution with the least impact and most activities would continue as they do now.

Given that Theresa May vowed to exit the Single Market in January 2017, and that this status would not guarantee the UK pays less money to Europe, it would be politically difficult for the current UK government to promote this option. The Association of the British Pharmaceutical Industry however is pushing to reach an agreement to secure the ongoing cooperation between UK and Europe as fast and clearly as possible [12].

EFTA only (like Switzerland)

• Participate with the ESM (four freedoms) but not to the European Union Customs Union
• Switzerland is the only one of four EFTA members that is not an EEA member: instead of using the rules defined under the EEA membership, it has a set of bilateral agreements with the European Union.
• EMA evaluation and EC marketing authorization do not apply here, approval must be obtained from SwissMedic (Swiss Agency for Therapeutic Products) before being commercialized locally.

The UK would retain access to the Single Market.

However, the UK would need to locally approve drugs. This would cause delays as the MHRA is not staffed to handle this extra burden. This would also double the regulatory burden for US companies, as they would need to file once with EMA and once with MHRA, both agencies not having necessarily the same requirement, timelines and dossier format.

WTO (like the rest of the world)

• Default model: need to negotiate bilateral trade agreement on everything including trade and customs.
• EMA evaluation and EC marketing authorization do not apply here, approval must be obtained locally.

The UK would no retain access to the Single Market: trade agreements would have to be negotiated, which would hinder drug movement, both those produced in the UK and exported to continental Europe, and those produced in Europe trying to reach UK patients. Although a 0% tariff on pharmaceuticals is most likely (under the Most Favoured Nation status), other goods could experience tariffs (esp. medical devices). GMP certifications would also be subject to bilateral agreement.

The UK would need to locally approve drugs with the same consequences as the EFTA only scenario.

As negotiations progress at a pace slower than expected, some companies have already activated their contingency plans to mitigate the WTO scenario: Eisai and AstraZeneca have started exploring approval and testing procedures outside of UK. Others, like GSK, are about to invest money to develop their own contingency plans [13].

Conclusion:

While the UK would remain an attractive market, it is currently hard to foresee which version of the three scenarios will materialize: entry to Europe and UK will become a more complicate, prompting for expertise at the regional level to optimize market entry strategies in a timely manner.

As the UK may put some space between itself and the EU, there is hope that ties with the members of the Commonwealth of Nations, (especially Australia, Canada, and India), could be strengthened. In this case, UK could shift from a US foothold in the EU to a US foothold in other high-growth areas of the globe.

References

1° http://www.bbc.com/news/health-38887694, Accessed Nov 08th 2017

2° https://www.gov.uk/government/publications/why-overseas-companies-should-set-up-in-the-uk/why-overseas-companies-should-set-up-in-the-uk, Accessed Nov 08th 2017

3° https://www.gov.uk/guidance/corporation-tax-research-and-development-rd-relief, Accessed Nov 16th 2017

4° https://en.wikipedia.org/wiki/European_Single_Market, Accessed Nov 08th 2017

5° https://ec.europa.eu/unitedkingdom/news/european-research-council-10-%E2%80%93-uk-top-beneficiary_en, Accessed Nov 17th 2017

6° https://royalsociety.org/~/media/policy/projects/eu-uk-funding/phase-2/EU-role-in-international-research-collaboration-and-researcher-mobility.pdf, Accessed Nov 16th 2017

7° https://www.kcl.ac.uk/sspp/policy-institute/publications/SpilloversFINAL.pdf, Accessed Nov 16th 2017

8° http://www.sciencecampaign.org.uk/asset/F50CF4C1-93C7-4F38-89E55D6BDBB70ED6/, Accessed Nov 16th 2017

9° http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000629.jsp, Accessed Nov 08th 2017

10° https://www.unified-patent-court.org/, Accessed Nov 08th 2017

11° https://infacts.org/norwegians-pay-same-brits-eu-access/, Accessed Nov 08th 2017

12° http://www.abpi.org.uk/media-centre/Documents/BARNIER_DAVIS_Joint_Association_Pharma_Letter_12_July_2017.pdf, Accessed Nov 08th 2017

13° https://www.economist.com/news/britain/21731409-industry-long-production-timelines-cannot-afford-wait-any-longer-pharmaceutical-firms Accessed Nov 17th 2017

European biosimilar market: a tremendous opportunity with variable market access constraints

With the recent recommendation of an anti-cancer blockbuster biosimilar by the EMA, the market has the opportunity to soar. Driven by the fierce interest of payors for affordable alternatives to many biologics, national authorities proactively push for biosimilar adoption. To be successful, players must understand the specifics of each market and tailor their strategy accordingly.

The global market opportunity for biosimilars is emerging as a result of three factors. Through 2020, 30 blockbuster biologics, which achieved $109 billion global sales in 2016, face loss of patent exclusivity in at least one major market. In these major markets, regulatory agencies have now defined appropriate regulatory pathways for the approval of new biosimilars. Moreover, the implementation of cost containment practices on the part of governments and insurers has increased demand for such high-quality and less costly versions of blockbuster biologics. Europe dominates the market for biosimilars, but a sharp understanding of specific national attributes is required for players to perform.

EMA has been a pioneer in biosimilars regulation

In the early 2000s, the EMA led the way in establishing regulatory guidelines for the development and assessment of biosimilars, nailing down key principles that have subsequently been adopted worldwide. The EMA regulatory processes’ efficiency is demonstrated by the successful approval of 32 biosimilars already (vs. 10 in the US).

The last update of EMA biosimilar guidelines (2014-2015) attests to its will to evolve in recognition of: technological advances, accumulated experience with marketed products, and availability of new biosimilar targets. The EMA now allows clinical trials conducted outside Europe to be used for biosimilar filing, saving costs of an extra clinical trial for the sponsor. The updated guidance also addresses specific issues to ease the development of complex biosimilars (e.g. monoclonal antibodies), such as the amount of immunogenicity data needed. Furthermore, biosimilar makers can now benefit from EMA’s “Biosimilars Project” which offers free and tailored scientific advice for the development of new targets based on the originators’ data (quality, analytical and functional) in EMA’s possession.

Substitution policies are within the remit of each country

The EMA centralized procedure does not require a switching study to grant approval to biosimilars and substitution policies are within the remit of each European country. Although EMA considers approved biosimilars as equivalent therapeutics alternatives to biologics, automatic substitution is not routinely performed, mainly due to concerns regarding traceability and to the potential impact of repeated switching on immunogenicity. In some countries (UK, Italy, Spain, and Nordics), guidelines or laws prohibit automatic substitution whereas in others (France, Netherlands, Poland, and Baltics), automatic substitution is implemented at the pharmacist or physician level. For biosimilar makers not familiar with European markets, national policies can sometimes be confusing: in Finland and Germany, national authorities (respectively the FIMEA and the Paul-Ehrlich-Institut) consider biosimilars interchangeable with their reference biologicals, however automatic substitution is not included in their current recommendations, which in the end leaves the prescriber with the decision between originator and biosimilar. In this uncertain and quickly evolving environment, biosimilar makers which are able to provide strong switching data have a certain competitive advantage.

Nordic countries are at the forefront of the real-world clinical evidence gathering effort

The initial resistance that followed Europe’s first biosimilar approval in 2006 shows that physicians’ confidence cannot be taken for granted, because of biosimilars’ high complexity and of the stakes for targeted patients. Therefore, payors are aware that forcing biosimilars adoption for cost reasons alone cannot work. Consequently, European countries have been at the forefront of the real-world clinical evidence gathering effort. In Norway, the NOR-SWITCH study has been pivotal in proving biosimilars quality reliability and clinical equivalence with their originators. Funded by the Norwegian Ministry of Health, NOR-SWITCH examined switching from originator infliximab to biosimilar CTP13 in about 500 patients and showed that switching was not inferior to continued treatment with originator. NOR-SWITCH triggered a radical changed in physicians’ perception, spurring the infliximab biosimilar to a market share above 90%.

Policies targeting biologics procurement strongly enhance biosimilars adoption

Backing biosimilars with high quality data is not sufficient to drive uptake. National voluntarist policies are needed at the procurement level. Indeed, despite payors clear benefit from biosimilar usage, there might not be any financial incentives for the hospital, physician or patient to use the biosimilar.

In Nordic countries, the impressive uptake of biosimilars provides sharp insights on the impact of procurement-level strategies. In Norway, epoetins were originally covered by general reimbursement, thus neither the patient nor the physician recognized the biosimilar-associated savings, leading to little switching and low uptake. In 2016, epoetins were transferred to hospital tenders. Two months later, the epoetin biosimilar had gained a 65% market share. This drastic switch was enabled by cost containment awareness among physicians, but also due to an efficient electronic prescription system on which physicians could quickly and massively recall their patients’ prescriptions. In Finland and Denmark, biosimilars also deeply penetrate the biologics market because of strong financial incentives and a management push for biosimilars in hospitals. Opinion leaders often use the NOR-SWITCH study results as a key argument.

Incentives strongly facilitate biosimilars adoption

Tendering at hospital level does not automatically drive biosimilars adoption. Payors must closely monitor the actual adoption at hospital level. For instance, in Ireland and Belgium, although hospitals can procure biologics by competitive tendering, until recently they were indirectly incentivized to purchase the highest price product because they could keep the discount, which are larger for more expensive products. In Spain, some regions such as Madrid have contracts with hospitals to closely monitor the uptake of biosimilars and reward the hospitals that comply with the contract objectives. Prescription quotas can also be installed to force the adoption of biosimilars. In Germany, different prescription minima are set by each regional insurer to promote the use of biosimilars, with physicians being financially threatened for not achieving their objectives. Similar quotas exist in Italy, along with specific education programs designed to foster the use of biosimilars. Consequently, Germany and Italy are now among the top adopters of biosimilars in Europe.

An alignment of positive positions from expert societies, medicine agencies and hospital management, along with financial incentives, is key to fully drive biosimilars adoption. In all countries that enable such collaborations between payors and prescribers, the biosimilars market share is significant. For players, success then strongly depends on their capacity to find the right contracting channel, which is reliant on: the national market structure and clinical practices, and their therapeutic area. Therefore, players must adapt their business models depending on the country-specific market access conditions. But in a market regulated by an agency continually renewing its effort to closely accompany biosimilar makers with an adapted framework, and where 80% of physicians are incentivized to use biosimilars, opportunities cannot be missed.

Information and points of view disclosed in this article are based on Cepton’s knowledge and on the following sources, which we recommend reading:
1. Schiestl M, Zabransky M, Sörgel F. Ten years of biosimilars in Europe: development and evolution of the regulatory pathways. Drug Design, Development and Therapy. 2017;11:1509-1515. doi:10.2147/DDDT.S130318.
2. Scott Morton, Fiona, Ariel Dora Stern, and Scott Stern. “The Impact of the Entry of Biosimilars: Evidence from Europe.” Harvard Business School Working Paper, No. 16-141, June 2016. (Revised July 2017.)
3. Generics and Biosimilars Initiative online resources

Managed Access Programs (MAPs) provide patients with anticipated access to drugs before their full-fledged commercialization. As often seen in Europe, the situation is complex: on one hand, MAPs can refer to several different schemes within a country, on the other hand MAPs are regulated at country level, with almost as many situations as there are countries. Yet, MAPs are an integral part of a successful market entry strategy for Europe. How can you maximize your chances to implement a successful MAP that will help the patients in need and speed up your adoption by the medical community?

What are MAPs and why are they necessary?

While market authorization can now be granted at a European Level, “Pricing and Reimbursement” are still the prerogative of each Member State: in some countries, a drug can fall into the paradoxical state where it is approved and yet cannot be prescribed, for lack of reimbursement. To mitigate this problem, Managed Access Programs have emerged in most European countries.

MAPs are programs designed to accelerate patient access to new, efficacious drugs, in an ethical, compliant, and controlled way until they become fully marketed (approved, with price and reimbursement schemes in place). MAPs bridge the gaps that exist between clinical trials and commercially available drugs: they are usually set up once phase III results are known, and the marketing authorization has been filed, i.e. even before the marketing authorization is granted.

For the sake of clarity, MAPs in this article will be considered to be mostly Compassionate Use Programs, but be aware that the term “MAP” sometimes has a broader definition and could be used interchangeably with – or include – programs such as Early Access Programs, conditional approval, PriMe (Priority Medicine scheme) …

Even within a given country, MAPs could either concern individual patients or groups of patients. The first case is referred to as NPP for Named Patient Program, the second as Cohort Programs.

Who will benefit from a MAP?

The patients

Getting access to effective medicine when no other option is available: the benefit to the patient is obvious.

One way for patients to receive treatment early is to be included into clinical trials (e.g. Open label extension after the randomized phase of the pivotal trial), but not all patients are eligible to participate in the trials, which are protocol-driven and have stringent inclusion and exclusion criteria. Thus, MAPs are often the only option for patients who cannot wait for the drug to be commercialized and cannot enter clinical trials.

Furthermore, MAPs are validated by local authorities and the drug can only be distributed through well defined channels, reducing the risk for counterfeit drugs.

The physicians

For physicians, MAPs are extremely useful as well, because on top of the direct benefit it provides to their patients, it also allows them to better understand the drug and have their first hands on experience with a new drug.

It can also please the early adopters within the physician population, who, once convinced of the benefits the drugs bring to patients, can become the best brand advocates, whether to recommend to their colleagues or to intervene as experts during pricing and reimbursement negotiations.

The payers

Most compassionate use programs require the drug to be provided free of charge by the market authorization holder (MAH). Some named patient programs and the Autorisation Temporaire d’Utilisation in France (ATU, ‘Temporary Authorization for Use’) are the exception to the rule: the healthcare system would pay for the drug in this case.

The MAH still takes care of the pharmacovigilance (PV): this provides safety data from a larger population sample in a more “real-life” setting, which helps better assess the safety, tolerability, and Quality of Life aspect of the reimbursement and pricing negotiations.

The market authorization holder

Despite having to provide the drug for free in most cases and assuming the costs of PV, some associated benefits have been noticed as MAPs became more common:

• Patient-centric company image: MAPs show the goodwill of the company towards patient needs, which helps strengthen the ties between the MAH, the medical community (both KOL and community prescribers) and the patient advocacy groups. Furthermore, it increases the likelihood that patients try the treatment offered through the MAP instead of others.
• Spontaneous awareness: More physicians and patients will experience the benefits associated with the treatment, which will likely fuel discussion among patient groups. This increased spontaneous (i.e. non-promoted) awareness will more likely speed up the widespread medical adoption once the drug is commercialized. It is likely it has an impact on the 1st year market share[i] (a gain close to 1/3 in terms of market share was loosely associated with the implementation of a NPP in a small retrospective study).

However, one cannot stress enough that the primary goal of a compliant MAP should be to provide efficacious treatments to patients with unmet needs.

Diversity of schemes across Europe

The diversity of programs available in France (FR), Germany (DE), Italy (IT), Spain (ES) & the United Kingdom (UK) illustrates the complexity of setting up a European MAP for a newly approved drug:

Absence of global EU framework: Within the scope of Article 83 of Regulation (EC) No 726/2004, the EMA provides recommendation through the Committee for Medicinal Products for Human Use (CHMP), but does not create a single legal framework.

There are 5 different authorities to coordinate:

• Agence nationale de sécurité du médicament et des produits de santé (ANSM, FR)
• Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM, DE) & Paul-Ehrlich-Institute (PEI, DE)
• Agenzia Italiana del Farmaco (AIFA, IT)
• Agencia Española de Medicamentos y Productos Sanitarios (AEMPS, ES)
• Medicines and Healthcare Products Regulatory Agency (MHRA, UK)

Diversity in program types: Cohort programs only (DE), Named Patient Program only (UK) or both cohort and NPP available (FR, ES, IT).

Conclusion

European MAPs are more complex than their US counterpart, with no centralized approach (yet). However, and despite their non-negligible cost, they provide benefits for all stakeholders within the healthcare ecosystem, including the market authorization holder. Thus, MAPs are an integral part of strategy to foster fast adoption by the medical community but require careful planning to reach their goals while keeping expenditure under control.

Cepton Strategies will be attending the JP Morgan conference in January. We would be delighted to discuss these points with you in detail and address your concerns for the European market. Please click here for more information and to get in touch.

[i] A.K. Bates, Journal of Medical Marketing (2008) 8, 319 – 324