The 2016 Rare Diseases & Orphan Products Breakthrough Summit, a two-day conference led by the National Organization for Rare Disorders (NORD), was held right outside of Washington D.C. in October. More than 600 participants had registered for the conference and delegates were excited about remarkable medical advances and the potential for future collaborations in the rare diseases space.

One of the key themes woven throughout the conference proceedings was the widespread adoption of gene technologies in drug development in rare diseases. Many rare disorders are caused by genetic defects and so gene technologies are uniquely suitable to target the underlying cause of these disorders, where the unmet need is often high. The rapid development of genome sequencing, new adeno-associated viral and lentiviral vectors, small interfering RNAs (siRNAs), antisense oligonucleotides, and CRISPR/Cas9 gene editing, have driven an explosion in the number of gene technologies in development for treating rare diseases.

Another topic often discussed at the conference was hurdles to patients’ access to drugs. Orphan drugs usually carry a high price tag and are dispensed through specialty pharmacies in the United States; collectively, the cost of covering orphan drugs continues to increase. Although high unmet need is still a key element that supports the coverage of expensive orphan therapies, payer resistance to reimbursement is increasingly observed when orphan drugs lack solid evidence of clinical benefits.

For instance, payers had different responses regarding the recent accelerated approval of Sarepta’s Exondys 51, an approval that was based on a small size trial and a surrogate biomarker for efficacy. Exondys 51, with a net average price of $300,000 per year as reported by its developer, is the first FDA-approved therapy targeting the underlying cause of Duchenne muscular dystrophy, a devastating disease affecting young boys. U.S. payers Cigna and United Healthcare will reportedly cover the drug, but Anthem decided not to reimburse for this agent, stating that the therapy is “investigational and not medically necessary" (Anthem Exondys 51 Medical Policy). It’s still unclear if in practice reimbursement of Exondys 51 for patients under Anthem plans could still be considered on a case by case basis. Another insurer, Aetna, reportedly plans to conduct their own clinical review of Exondys 51 before making any commitment.

Over the last few decades, the FDA has been very supportive of orphan drug development. Many approved orphan drugs enjoyed regulatory flexibility (for example, approval was based on one adequate and well–controlled [AWC] clinical trial and supportive evidence, instead of two or more AWC efficacy trials2) and faster approval time under one or more expedited or facilitated review programs, including priority review, fast track designation, accelerated approval, and breakthrough designation. However, the recent approval of Sarepta’s Exondys 51 was not considered “a good model for other development programs”, according to John Jenkins, director of the Office of New Drugs at the FDA’s Center for Drug Evaluation and Research (CDER), due to the use of biomarkers that were not well validated and the lack of rigorous blinding and control procedures. While the FDA can be flexible to a point regarding the clinical development of orphan drugs, the flexibility would not extend to approval of agents lacking solid evidence of effectiveness and safety (for additional analysis regarding the potential consequences of the unorthodox approval pathway of Exondys 51, see our previous blog: How Might the Aftermath of Eteplirsen’s FDA Approval Shape the Future Clinical and Commercial Landscape in Duchenne Muscular Dystrophy?).

Overall the summit presented an incredible opportunity for meeting key stakeholders in the rare disease area. The continued collaboration between public health agencies, the patient community, and drug manufacturers will be sure to increase the number of treatments available to rare disease patients.

For a more in-depth analysis of market access dynamics for orphan drugs in the United States and Europe, please see our recent contents Duchenne Muscular Dystrophy,  Orphan Drugs | Access & Reimbursement | US and Orphan Drugs | Access & Reimbursement | EU.

  1. Sokolic R, et al. Gene therapy investigational new drug applications for rare diseases at FDA’s Center for Biologics Evaluation and Research. 2016 NORD Summit Poster.
  1. Feng J, et al. Drug review trends in new orphan drug applications approved by FDA Center for Drug Evaluation and Research from 2008 to 2015. 2016 NORD Summit Poster.

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