FDA program aims to support developers of rare disease therapies

More communication, better 'insight' expected with new START pilot

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The U.S. Food and Drug Administration (FDA) has launched a pilot program, dubbed START, to accelerate the development of therapies for rare diseases like aromatic l-amino acid decarboxylase (AADC) deficiency.

Called, in full, the Support for clinical Trials Advancing Rare disease Therapeutics Pilot Program, the START initiative will enable a limited number of rare disease therapy developers — to be called sponsors — to have more frequent communication with the regulatory agency. The ultimate goal of the START program is facilitating the clinical development of these sponsors’ therapeutic candidates.

The FDA will be accepting START applications between Jan. 2 and March 1 of next year.

“We hope the insight gained from this pilot will provide information on how best to facilitate more efficient development of potentially life-saving therapies with rare disease indications and help sponsors generate high-quality, compelling data to support a future marketing application,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research (CBER), said in an agency press release.

“These are complex products and we recognize the importance of sponsor communication with the FDA to facilitate development of products for patients with unmet medical needs,” Marks added.

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START program could be used to advance AADC deficiency treatments

In the U.S., a rare disease is defined as one affecting fewer than 200,000 people nationwide. There are more than 7,000 rare diseases, cumulatively affecting more than 30 million people in the U.S., according to the FDA.

This includes AADC deficiency, an extremely rare genetic disorder estimated to affect about 1-3 newborns per 100,000 live births in the U.S. The disorder impacts the nervous system, hindering communication between nerve cells, and results in severe delays among children in reaching developmental milestones.

The rarity of conditions such as AADC deficiency means that companies don’t have as much financial incentive to develop treatments.

To combat this issue, the government passed the Orphan Drug Act in 1983. Under this legislation, rare disease therapies that are granted orphan drug designation from the FDA provide their sponsor certain financial incentives and regulatory support to encourage their development.

The START program will be another effort from the regulatory agency to accelerate the development of treatments for rare diseases.

Program participants will be able to obtain frequent advice and communication with FDA staff to address development issues related to their therapeutic candidate, such as clinical trial design and selection of study populations, including appropriate control groups.

Sponsors of therapeutic candidates that are now in clinical trials in the U.S. under an active investigational new drug application will be eligible to apply for the pilot.

This includes applications overseen in two different departments — CBER and the Center for Drug Evaluation and Research (CDER) — each involving distinct eligibility criteria.

CBER-regulated candidates must be a gene or cellular therapy intended to address an unmet medical need for rare or serious conditions that are likely to result in significant disability or death in the first 10 years of life.

CDER-regulated candidates must be intended to treat rare neurodegenerative conditions, including those caused by metabolic defects of genetic origin.

Up to three participants from each CBER and CDER will be selected based on the sponsor’s demonstrated ability to move its clinical development program forward toward a marketing application for U.S. approval.

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Other efforts underway to speed therapies for rare diseases

Sponsors will receive support in START until their therapeutic candidate has reached a predefined regulatory milestone. For example, this could include initiation of a pivotal clinical trial to back the filing of a marketing application, or holding a pre-filing meeting with the FDA.

Should the pilot program be successful, the FDA may consider another round of the program at a later date.

We [at the FDA] share the goal of delivering potentially life-saving products to patients, and are committed to helping sponsors achieve regulatory milestones, while ensuring the safety, effectiveness and quality of these products.


“We look forward to increased engagement with sponsors developing these important products for the rare disease community,” said Patrizia Cavazzoni, MD, director of CDER, adding, “We share the goal of delivering potentially life-saving products to patients, and are committed to helping sponsors achieve regulatory milestones, while ensuring the safety, effectiveness and quality of these products.”

Meanwhile, the FDA also is engaging in other efforts to facilitate rare disease therapy development, including plans to publish guidance documents related to cell and gene therapies.

The agency also is seeking feedback from stakeholders related to the opportunities and challenges in developing cell and gene therapies for rare diseases, as well as the development and dissemination of educational materials related to rare disease drug development.

Information gained will be used to support workshops, educational meetings, and other publicly available resources to help facilitate rare disease therapy development.

The FDA recently shared a draft guidance on how to classify and use confirmatory evidence from sources such as clinical, mechanistic, and animal studies to supplement efficacy data from well-controlled clinical trials. Guidance documents for cell and gene therapy development are expected to be published in the near future.