Strategic Patient Advocacy vs. Evidence Package: The “Rare” Challenge for Orphan Drug Manufacturers

On September 19, 2016, the USA FDA granted accelerated approval to $SRPT (SAREPTA THERAPEUTICS) lead product, EXONDYS 51™(eteplirsen), the first targeted treatment for (DMD), a devastating rare disease. What makes the case unusual is that in approving EXONDYS 51™, the FDA went against the recommendation of its Advisory Committee, a decision at least partly influenced by patient advocacy activities, an increasingly powerful force in drug development, regulatory approval, and commercialization.

FIGURE 1. Impact of Patient Advocacy on Regulatory Approval for EXONDYS 51™ in the USA

EXONDYS 51™‘s review got off to a rocky start in January 2016 with a negative FDA Advisory committee report (Figure 1). The committee criticized $SRPT’s main clinical trial due to its size, design and unsatisfactory assessment of the main clinical endpoint, the 6-minute walk test. Patient advocacy groups quickly mobilized in support of EXONDYS 51™. They promoted a letter of support signed by 36 clinicians defending the trial results. They lobbied congressional representatives, who in turn put pressure on the FDA. They packed the room at an FDA external advisory board hearing in April and presented their case directly to the members. Still, the external advisory board voted EXONDYS 51™ down 7-6.

Moving away from the clinical outcome and focusing on a proxy indicator, FDA asked $SRPT to provide additional evidence showing increased expression of dystrophin, the gene mutated in DMD, in patients enrolled in an ongoing trial. Despite disappointing results from this request, in September 2016 FDA finally handed $SRPT a positive accelerated approval. The decision causedturmoil in the FDA and resulted in a JAMA article by an external FDA expert strongly criticizing the case and advocating against a repeat.

The post-approval positive mood surrounding Sarepta was tempered when early reports started to suggest insurers might present an obstacle to access due to the USD 300,000 per year price tag and limited clinical efficacy data (Figure 2). ANTHEM ($ANTM), the second largest commercial insurer in the USA, announced that they consider the drug “investigational and not medically necessary” and did not expect to provide coverage. Other payers agreed to cover, but with restrictions. A recent survey of payers demonstrated that only 45% of potentially prescribed patients are expected to have their therapy approved for reimbursement by their respective insurers.

Patient Project MD (PPMD), the largest US non-profit supporting DMD families, sided with $SRPT, and announced that they would work with the biotech to reverse $ANTM’s decision to not provide coverage for EXONDYS 51™. While $SRPT’s regulatory success has incentivized Patient Advocacy Groups (PAGs) and orphan drug manufacturers to join forces, the evidentiary requirements from commercial plans remain rather unchanged. While PAGs can push the case, the evidence package is still the dominant factor determining the extent and urgency of reimbursement, which in turn represents the greatest potential challenge for commercial success in the USA (and beyond).

On the other hand, PPMD, was recently critical of MARATHON PHARMACEUTICAL’s decision to charge USD 89,000 annually for another DMD product, EMFLAZA™ (deflazacort), calling the price “hefty”. The active ingredient, deflazacort, has been available outside the USA for decades, and was previously being imported by some USA-based patients at generic level prices (approximately one dollar per 6mg tablet), which likely explains PPMD’s lack of enthusiasm. After MARATHON paused the launch, PPMD suggested discussions including all stakeholders to agree on a new price.

FIGURE 2. EXONDYS 51™ Coverage Among USA Commercial Health Plans

Figure 2 from PPT

Outcomes of EXONDYS 51™ and EMFLAZA™ cases are the latest indicators of the power of patient advocacy in the effort to clear regulatory and market access barriers.  While the impact on regulatory decision-making is still quite palpable, their ability to affect commercial payers in the USA may still be behind their ability to influence similar decisions in other countries.  As the role of value frameworks and pathways develop in line with large payers’ ability to create exclusion lists based on non-coverage decisions, the role of patient advocacy is likely to expand to greater levels in the pursuit of reimbursement among commercial payers in the future.

CBPartners advises orphan disease drug manufacturers regarding their pricing, market access and commercialization strategy in the USA, Europe / other development markets, and the emerging markets.