HTA Regulation

Getting gene therapies to market faster

The FDA approval process is slow. Even for COVID-19 vaccines, the process can be time consuming. However, regulators around the world do have some expedited programs. However, a number of countries have programs that expedite review, particularly for the diseases with unmet need, orphan drugs, or when new treatments represent a significant advance over the standard of care. Wang et al. (2020) summarizes some of these programs as follows:

Fast Track
Facilitate development and expedite the review of drugs to treat serious conditions and fill an unmet medical need
USBreakthrough therapyExpedite review of drugs with the potential for substantial improvement over available therapy
USRegenerative Therapy Advanced DesignationIncludes all benefits of fast track and breakthrough, includes early interactions with FDA
USPriority Review designationFDA goal is to make a decision on the application within 6 months
EuropeConditional market authorizationAvailable for medicines that address unmet medical needs where the benefit of immediate availability outweighs the risk of a less comprehensive review
EuropeApproval under exceptional circumstanceMarketing authorization in absence of comprehensive data that cannot be obtained even after authorization
EuropePriority medicine (PRIME) designationEMA scheme to support development of medicines that target and unmet medical need
JapanTime limited, conditional market authorizationMarketing authorization conditional on further data. Conditional approval may last a maximum of 7 years
JapanSAKIGAKE designationProgram aiming to accelerate the application of innovative drugs for serious and life-threatening diseases
JapanRegenerative medicine specific orphan drug designationAllows subsidy to cover direct expenses of the development and authorization of orphan products indicated for serious diseases with high medical needs
JapanPriority reviewDesignation means that Pharmaceuticals and Medical Devices Agency (PMDA) review time is reduced to 9 months(from a standard 12 months review)

The article discusses in detail some of the regulatory rules for gene therapy approval. At the time the article as published, 7 gene therapies had received marketing authorization. These are:

  • Glybera (alipogene tiparvovec). Approved for familial lipoprotein lipase deficiency under exceptional circumstance in Europe.
  • Imlygic (talimogene laherparepvec). Approved for unresectable melanoma in Europe under standard approval (with additional monitoring) and in the US through a fast track approval.
  • Strimbelis (autologous CD34+ cells transduced to express ADA). Approved to treat severe immunodeficiency due to ADA deficiency in Europe under standard approval (with additional monitoring).
  • Yescarta (axicabtagene ciloleucel). Approved for B-cell lymphoma under PRIME in Europe and under a breakthrough therapy designation and priority review in the US.
  • Luxturna (voretigene neparvovec). Approved for the treatment of retinal dystrophy under orphan designation with additional monitoring in Europe and breakthrough designation/priority review in the US.
  • Kymriah (tisagenlecleucel). Approved to treat acute lympblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL) under PRIME in Europe and under breakthrough designation/priority review in the US.
  • Zolgensma (onasemnogene abeparovovec-xioi). Approved to treat spinal muscular atrophy in Europe through conditional marketing authorization with additional monitoring and in the US under breakthrough designation/priority review.

Even after marketing approval, payers must determine whether they will cover these treatments. The authors conclude their article on this latter issue as follows:

 Various approaches have been adopted by different countries to mitigate the potential risk of reimbursing gene therapies with substantial uncertainties surrounding long-term outcomes. Payers generally have expressed openness to such innovation. However, it is questionable how they will react and deal with the continuously increasing number of gene therapies seeking market access.

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