Update: Advisory Committee Meeting for Translarna


The U.S. Food and Drug Administration (FDA) on Thursday will convene a meeting with the Peripheral and Central Nervous Systems Drugs Advisory Committee (PCNS), to review the new drug application, or NDA, for ataluren (brand name Translarna) to treat some forms of Duchenne muscular dystrophy (DMD).

The FDA is expected to make a decision on Translarna on or before Oct. 24.

What is an FDA advisory committee meeting?

Part of the FDA mission is to evaluate new therapies and determine which are safe and effective for their intended use. Advisory committees provide the FDA with independent advice from outside experts on issues related to human and veterinary drugs, vaccines, medical devices and food.

The PCNS Advisory Committee reviews and evaluates data concerning the safety and effectiveness of marketed and investigational human drug products for use in the treatment of neurologic diseases and makes appropriate recommendations to the Commissioner of Food and Drugs. One of several dozen technical and scientific advisory committees, it is responsible for reviewing potential treatments for DMD.

Although the committee provides advice to the agency, the FDA makes the final decision on whether to approve a new drug. To learn more about FDA Advisory Committee Meetings, visit: Common Questions and Answers about FDA Advisory Committee Meetings.

Translarna is designed to slow functional decline in DMD

Translarna is under development by PTC Therapeutics to treat DMD caused by a type of genetic mutation known as a “nonsense mutation” or “premature stop codon.” This type of mutation causes the muscle cell to stop reading the genetic code used to manufacture the muscle protein dystrophin before it reaches the end, thus preventing production of the protein.

A “read-through” drug, Translarna is designed to act by changing the way muscle cells interpret genetic information, coaxing them to produce dystrophin despite the presence of a nonsense mutation in the DMD gene. The drug, which is taken by mouth, may help approximately 13 percent of people with DMD.

MDA has contributed nearly $3 million towards Translarna’s development and phase 2 clinical testing.

Mixed trial results will be discussed by the committee

In October 2015, PTC announced results from its phase 3 “ACT DMD” clinical trial of Translarna, which demonstrated that the drug failed to meet its primary endpoint. However, a post-hoc analysis indicated that the drug may slow functional decline in a subset of DMD patients, while other patients were not responsive to treatment. Among those who responded, treatment was associated with statistically significant improvements to several clinical outcome measures.

Translarna received “conditional approval” in the European Union in August 2014 for use in people with DMD caused by a nonsense mutation who are at least 5 years old and able to walk.

NDA for Translarna filed over protest

PTC completed submission of its NDA to market Translarna in the U.S. in January 2016, but in February received a Refuse to File letter from the FDA stating that the application was not sufficient to permit a substantive review. It submitted an appeal in July to the next level of FDA management and reported in October that the appeal had been denied.

PTC used the FDA’s “file over protest” regulations to file the NDA. These regulations allow a company to have its NDA filed and reviewed following a refuse to file determination.

The critical requirement remains that substantial evidence of effectiveness must be provided in order for the FDA to support approval of a new drug.

Advisory committee meeting details

The meeting is scheduled to take place on Thursday, Sept. 28, from 9 a.m. to 4:30 p.m. ET., at the Tommy Douglas Conference Center in Silver Spring, Md.

The FDA has made available background materials and webcast information for the advisory committee meeting on its website.

To view the complete set of background information including a meeting agenda, meeting roster, committee roster and briefing information, visit 2017 Meeting Materials, Peripheral and Central Nervous System Drugs Advisory Committee.

The Center for Drug Evaluation and Research (CDER) plans to provide a free of charge, live webcast of the meeting, beginning at approximately 9 a.m. ET. The webcast will be archived and posted following the meeting.

View the live webcast here, or copy the following URL into your browser: http://fda.yorkcast.com/webcast/Play/734c628502b84ae2baedc5fa6c5db5b41d.

MDA involvement

It is the role of the FDA to examine the data for new drugs and make a determination about whether each is safe and effective enough to be marketed.

MDA’s aims with regard to engagement in the FDA’s Advisory Committee process are to share our commitment to helping find safe and effective treatments and cures as quickly as possible, and to emphasize that the importance of interrupting the course of disease cannot be overstated, and slowing disease progression is a critical and meaningful step in that process.

MDA submitted written comments to the FDA earlier this month and MDA Scientific Program Officer Laura Hagerty, Ph.D., will deliver MDA’s oral comment at the meeting.

As an organization with more than 65 years of research and clinical care experience, our message to the agency, committee, and to the DMD community is that DMD is a serious — and lethal — disease for which there are few treatments and no cures. While there are more treatment options than ever before available to DMD families, an unmet medical need continues to exist for those living with Duchenne. While we all work tirelessly toward a cure, the opportunity to safely and effectively slow disease progression is essential.