HIGH IMPACT – The European Commission (EC) has granted conditional marketing authorization (CMA) to ROCTAVIAN (valoctocogene roxaparvovec) gene therapy for the treatment of severe hemophilia A in adults without Factor VIII inhibitors and without antibodies to AAV5.

  • Roctavian is the first approved gene therapy for hemophilia A.
  • BioMarin stated there are 3,200 patients who will be indicated for Roctavian within the 24 countries covered by the EMA approval.
    • Reiterated survey data that they expect 35% of eligible patients to be treated at peak and 80% of providers will prescribe to at least one patient
  • BioMarin reiterated it will seek to expand access outside the EU through named patient sales based on the EMA approval in the Middle East, Africa, and Latin America
  • The EC decision was based on:
    • Two-year outcome data from the Phase 3 GENEr8-1 study showed a reduction in the mean ABR and mean annualized FVIII consumption rate
    • Five and four year follow up data from the ongoing Phase 1/2 dose escalation study
  • The CMA recognizes that the benefit to public health of the immediate availability of Roctavian on the market outweighs the uncertainties inherent to the fact that additional data are still required. Standard marketing authorization will be contingent upon the provision of additional data:
    • Longer-term follow up data from Phase 3 GENEr8-1
    • Data from trial investigating efficacy and safety of Roctavian with prophylactic use of corticosteroids (enrollment now complete)
  • The EC also endorsed EMA’s recommendation for Roctavian to maintain orphan drug designation, thereby granting a 10 year period of market exclusivity versus similar medicines with the same therapeutic indication.
    • In response to question, noted that exclusivity will not have a huge impact because next hemophilia A gene therapies are far away from reaching market
  • BioMarin is targeting a BLA resubmission in the US for Roctavian by the end of September 2022
    • An additional three months of review may be required based on data read-outs that will occur during the review period
    • In the Q&A, the company stated that the BLA resubmission does not require data from the prophylactic steroid trial. They also stated that the EU CMA bodes well for U.S. approval

BioMarin hosted a conference call to discuss Roctavian’s EU approval, launch plans, and pricing agreements:

  • On the call: Jean-Jacques Bienaimé (CEO), Henry J. Fuchs (President, Worldwide R&D), Jeff Ajer (CCO), Brian R. Mueller (CFO)
  • Details on the expected label:
    • Contraindicated for active infections and known liver issues
    • Patients will have liver health screened prior to treatment and one year after treatment
    • Warnings will include instructions for managing liver health, preferred corticosteroid regimen, possible thrombotic events, and possibility of vector genome integration (though expect SmPC to also state that AAV integration leading to cancer has never been reported)
    • The SmPC will contain the preferred corticosteroid regimen. In the Q&A, the company stated they expect most patients to require corticosteroids that will be tapered off within 6 months
    • Patients are expected to enroll in a registry to follow-up on safety and efficacy for 15 years
  • Launch details:
    • Currently finalizing payer agreement in Germany, expected to start dosing patients in Q4 2022
    • Applied for early access program in France and waiting on review. France will be second market
    • Spain and Italy will be 3rd and 4th markets, followed by markets across EU, Middle East, Africa, and Latin America
    • Launch metrics including number of active markets will be shared starting in Q3 earnings call and updated on earnings calls thereafter
    • In the Q&A, the company stated that Roctavian launch will only require marginal investment due to BioMarin’s strong global operations
    • When asked about early adopters, the company did not provide specifics but, as previously guided, they are looking at Hemlibra patients who are looking for superior outcomes as well as factor replacement patients who are not adequately controlled
  • Pricing details:
    • EU net price including discounts and expected rebates will be ~€1.5 mil
    • Outcomes based agreement will be customized for each payer, but general terms will be to collect total price then set agreement time frame (anticipating 5-8 years) and rebate cost of treatment-year if patient goes back on prophylaxis
      • Example given: If payer agreement is for 5 years and patient requires prophylaxis after 4 years, company will rebate 20% of upfront cost (1/5 treatment years not met).
    • List price for Germany will be shared in October
    • US price will be higher than EU prices. Price is modeled based on cost of current SOC. Current SOC is cheaper in EU than in US.
    • The assumed non-responder rate used to derive net price is around the non-responder rate seen in Phase 3 trial (6/134 or ~4.5%)
    • In the Q&A, the company stated they are confident about achieving reimbursement even though the approval was conditional due to the quality and quantity of the data so far

inThought Analysis

Conditional approval in the EU has been widely expected since the CHMP gave a positive opinion in June. As expected, the price of Roctavian is modeled off the cost of current SOC and the outcome based agreement with payers described on the call is in line with expectations. Outcome based agreements are becoming the preference among payers for gene therapy. Bluebird Bio described a similar outcome based agreement for their recently approved gene therapy for beta-thalassemia.

The expected approval of the first hemophilia gene therapy will be viewed as a major milestone in the development of hemophilia treatments and will generate significant excitement in the hemophilia community. While eligibility restrictions, pricing, concerns about long-term durability/ability to re-dose, among other factors, may limit the initial uptake, the launch of a new class of hemophilia treatments will prompt many HCPs/patients to revisit treatment options and will likely add to patients exploring the potential of new technologies.


Source: BloMarin Press Release