Earlier this month, we reached a big regulatory milestone: Prosetin received Orphan Drug Designation, or orphan status, for the treatment of ALS from the Food and Drug Administration (FDA). Here, we break down what orphan status means, why it’s important, and what it means for Prosetin’s potential clinical development.

What is Orphan Drug Designation?

The Orphan Drug Designation program was established by the Orphan Drug Act (ODA) of 1983, which recognized a critical problem in drug development—drug companies were not interested in developing treatments for so-called rare diseases including ALS because they could not expect to make a profit, or potentially even recoup development costs, based on limited numbers of treatable patients. The ODA offers financial incentives for companies that develop treatments for these rare diseases, defined in the bill as any disease which affects fewer than 200,000 Americans. ALS was actually named as one of a handful of representative diseases in the ODA, making potential treatments for ALS very strong candidates for orphan status.

The ODA contributed to sea change in drug development for rare diseases. In the 10 years before it was passed, only 10 industry supported products for rare diseases were approved by FDA. Since the ODA, more than 450 drug products for rare diseases have been approved—and in 2017, 39% of all new drugs that FDA approved were orphan drugs.

What benefits does orphan status confer?

Orphan status provides meaningful incentives and benefits for clinical drug development. Most notably, these include:

  • 7 years of market exclusivity from the date of approval – “Market exclusivity” is granted to drugs at the time of FDA approval, and means that for seven years after approval, no generic alternatives can compete with the approved orphan drug. Generally, new drugs only receive five years maximum of market exclusivity, so orphan status offers a significant extension.
  • 25% tax credit for clinical testing expenses – This credit helps to reduce the barriers typically presented by high costs of clinical development.
  • Waiver of PDUFA (Prescription Drug User Fee Act) fees for NDA – for any orphan drug that shows benefits in clinical development, the substantial filing fee (in 2021, $2,875,842) to actually apply for FDA approval is waived.

Orphan status also allows sponsors like Project ALS to compete for research grants from the OOPD and NIH to support clinical studies for developing orphan drugs, and to receive regulatory assistance and guidance from the FDA in the design of an overall drug development plan.

What does orphan status mean for Prosetin?

First, it’s important to note that Orphan Drug Designation is overseen by an independent group at FDA—the Office of Orphan Products Development (OOPD)—while FDA’s Division of Neurology I (DNI) is responsible for assessing the safety and efficacy of all potential drugs for ALS and other neurodegenerative diseases. This means that Prosetin receiving orphan designation does not have a direct impact on the timing or viability of any potential clinical trials, and Prosetin and all drugs that receive orphan status are still held to the same standards for safety and efficacy as all FDA-defined investigational drugs.

At the same time, orphan status provides new opportunities for Prosetin. In the near term, we are now eligible to apply for orphan drug specific research grants that could support more rapid, robust clinical development of Prosetin, and to seek additional FDA assistance and guidance toward our clinical trial design. Over the longer term, should Prosetin show benefits in clinical development, its orphan status will provide additional incentives to Project ALS and potential future partners to move it forward quickly.

With Prosetin, Project ALS aims to sponsor an investigational new drug for the treatment of ALS—a first for us or any ALS non-profit organization. We are committed to transparent updates every step of the way, and to sharing what we learn through this process with the ALS community. We’re proud that Prosetin has received orphan status, and remain focused on our goal of getting Prosetin to clinical trial as an FDA-defined investigational new drug as efficiently and responsibly as possible.