FDA Hearing Highlights ALS Drug Development Concerns

by Amy Madsen on Mon, 2013-02-25 17:41

Powerful testimony from individuals with ALS, caregivers, advocates and others will inform the FDA’s approach to the review and approval of new ALS therapies

Stanley Appel (center in red tie), physician-scientist and member of the MDA Board of Directors, gives testimony at the first-ever FDA hearing on ALS.
Article Highlights:
  • At a public hearing Monday, Feb. 25, 2013, conducted by the U.S. Food and Drug Administration, people with ALS and their families, clinicians and other medical professionals urged the FDA to consider the unique needs of patients and their families — for whom time is of the essence — when considering trial design and review of therapies for ALS.
  • Input in the form of verbal and written remarks was given by patients, caregivers, advocates, health care providers, academia, industry and others — including MDA President and CEO Steven M. Derks and Stan Appel, who directs the MDA/ALS Center at Methodist Neurological Institute in Houston.
  • The public may continue to submit comments to the FDA on this subject through March 25, 2013.
Update (Feb. 28, 2013): The daylong FDA ALS webinar has been archived and is now available for viewing on the FDA site.

At a standing-room-only public hearing Monday, Feb. 25, 2013, people with ALS and their families, researchers, clinicians and other medical professionals urged the U.S. Food and Drug Administration (FDA) to address the unique needs of patients and their families when considering the development of therapies for amyotrophic lateral sclerosis (ALS).

More than 200 people attended the hearing, titled, "Considerations Regarding Food and Drug Administration Review and Regulation of Drugs for the Treatment of Amyotrophic Lateral Sclerosis."  MDA was among the ALS patient organizations that played a significant role in prompting the FDA to conduct the first-ever hearing on ALS.

Those offering testimony included MDA President and CEO Steven M. Derks and longtime MDA research grantee Stan Appel, who is chairman of the Department of Neurology at the Methodist Neurological Institute in Houston and who directs the MDA\ALS Center at that institution. (Appel also is a member of the MDA Board of Directors and serves on its Translational Research Advisory Committee.)

Derks noted that the ALS patient and family community provides a "unique population" for FDA drug development regulation consideration.

"Patient perspectives," he said, "should be taken into account at every step of the therapy development and regulatory processes ... We are asking you to include these voices in your discussions regarding expanded access to trials, accelerated approval decisions and clinical trial design and enrollment.”

'A tremendous unmet medical need'

Appel noted that despite investments in infrastructure, natural history, basic science and clinical trials, the health outcomes for people with ALS have not changed sufficiently.

He proposed three main points, echoed by numerous other speakers throughout the day, to address the "tremendous unmet medical need" in ALS.

  • Prior to the initiation of efficacy trials, it may be necessary to design short, less-expensive clinical trials that can determine whether a drug can hit a therapeutic target.  Such trials could help scientists more quickly determine whether a potential therapy has any chance of success in treating ALS.
  • Because ALS can progress rapidly, accelerated review of devices such as noninvasive ventilation and cough-assist devices is necessary to improving quality and length of life. 
  • The symptoms of ALS — paralysis, loss of speech, loss of the ability to swallow and breathe — are in many ways equivalent to the possible side effects of experimental drugs. In other scenarios, they may be considered "intolerable," but the ALS patient community has demonstrated a willingness to tolerate significant risk. Withholding experimental therapy to prevent severe complications may be considered best practice, but a more informed risk-benefit analysis is needed for ALS.

Moving forward; overcoming regulatory barriers

Stem cell and neurobiology expert Clive Svendsen at Cedars-Sinai Medical Center in Los Angeles, urged the FDA to help research scientists speed discovery by eliminating regulations that require researchers to repeat work that has been done before. For example, it shouldn't be necessary to spend time demonstrating the safety of a particular procedure if the procedure has been determined to be safe in another trial.

Moving ahead quickly and efficiently is the goal, as noted by Svendsen and others.

"Regulatory barriers inhibit treatment, based on a traditional model that I believe should be updated," said neurologist Jonathan Glass, director of the MDA/ALS Center at Emory University School of Medicine in Atlanta. “A major impediment to developing new treatments is adherence to standardized paths that are counterproductive and do not address the complexities of this disease.”

Data sharing and the 'disease burden' of life with ALS

Other clinic team members, people with ALS and family members added their voices to the mix.

"Can we come together?" asked Mary Paolone, from the MDA/ALS Center of Hope in Philadelphia. "Can the FDA modify its policies and procedures to reflect the understanding that ALS is taking lives – human lives – at a rate that is simply unacceptable for this day and age?

Debra Quinn, who has ALS, suggested that technologies such as Skype and other forms of Web communication be considered in the introductory phases of clinical trials to help people with ALS avoid the cost and inconvenience of travel. Quinn also suggested that trial participants be allowed to continue receiving experimental therapies between trials.

Quinn's daughter Kristin shared her mother's sentiments, noting, "Today, more parents are sharing the family history of ALS with their children, and [they] understand and welcome scientific advances such as genetic testing and stem cell research.

"ALS patients have very little to lose, so I urge the FDA to give them more opportunity to leave a meaningful contribution behind."

Robert Anderson, who has ALS, was one of several speakers who addressed the FDA via prepared computer-generated speech. "We are gamblers on a big scale and any roll of the dice is better than ALS,” he said. "I ask that you join our fight as well. Give us the highest priority you can.”

For more information

Written comments about the hearing may be submitted online, through March 25, 2013, at Docket No. FDA-2013-N-0035 (click on the "Comment Now!" button), or via the United States Postal Service:

Division of Dockets Management
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852

The entire webinar is now available and has been divided into one-hour segments for easier viewing.

To learn more, read the comment recently submitted to the FDA by MDA and ALSA regarding these issues.

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