FDA Publishes Guidance to Help in Developing New ALS Therapies

FDA Publishes Guidance to Help in Developing New ALS Therapies

After gathering input from patients, researchers, and advocates, the U.S Food and Drug Administration (FDA) has released new guidance on the development of therapies for amyotrophic lateral sclerosis (ALS).

Among its recommendations, it is advising more communication with companies early on in the product development process, access to experimental therapies through compassionate use or the Right to Try Act, and broader inclusion criteria in clinical trials.

The final guidance, “Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment Guidance for Industry,” issued by the Center for Biologics Evaluation and Research, is intended to help companies and researchers develop new therapies, while providing the agency’s view of clinical trial designs and ways to measure effectiveness.

“We know the lack of new treatments for ALS is deeply frustrating for patients and caregivers,” reads a joint statement by Norman E. “Ned” Sharpless, MD, the FDA’s acting commissioner of food and drugs, Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, and Peter Marks MD, PhD, director of the Center for Biologics Evaluation and Research. “Staff from the FDA have been meeting regularly with members of the ALS community, including patients, their families and caregivers, and have heard their concerns loud and clear.”

One recommendation is for scientists and companies to interact with the FDA early in product development, so that the agency can advise the companies on how to carry out these programs and to efficiently design studies required to obtain regulatory approval. However, because the recommendations are non-binding, the agency “is open to considering alternative approaches to meeting our requirements for approval,” according to the statement.

Communication with patients is also key in helping companies understand how people with ALS view treatment goals and risks.

In clinical trials, all patients “should receive the best standard of care, and no patient should be denied effective therapies” as opposed to receiving a placebo. Companies also should not “unnecessarily exclude patients from trial enrollment based on characteristics such as age or disease stage,” although selecting specific groups may be justified.

To expedite trials and avoid the use of a placebo, the agency recommends approaches such as master protocols — a single infrastructure, trial design, and protocol to simultaneously assess different therapies with a common placebo group — and add-on designs, which test investigational medications in patients already on an existing ALS treatment.

In later stages of development, the companies may consider so-called decentralized studies, where methods including mobile technologies help collect data “in patients’ homes or by their local providers, to facilitate broader and potentially faster enrollment,” the guidance reads.

At all phases, the agency recommends incorporating exploratory biomarkers. Trials lasting six to 12 months should be sufficient to establish meaningful benefits, it says.

As for how to measure efficacy, the FDA recommends the ALS Functional Rating Scale-Revised or similar scales, patient-reported outcomes, assessments of muscle strength and respiratory function, as well as analyzing the effect on mortality. Yet, it supports “regulatory flexibility” with medical products for serious diseases including ALS, while still ensuring their effectiveness and favorable benefit-to-risk profile.

“As such, we stand ready to use the expedited development and approval programs available to help bring new treatments for ALS to patients as quickly as possible,” the statement says.

Another aspect covered in the guidance is patients’ willingness to seek out investigational products. The agency “remains committed to helping patients and health care professionals evaluate options,” which include participating in a clinical study, having access to an unapproved therapy through compassionate use or providing information about the Right to Try Act, which provides early access to experimental therapies to patients unable to join a clinical trial and who have tried all approved options.

Still, the FDA notes that companies must be willing to provide access to treatments under compassionate use and Right to Try. It also encourages companies to offer access to treatment candidates after trial completion “when continued access to a promising medicine would be appropriate under the expanded access program.”

The agency also asks pharmaceutical companies to provide updated information about their research in ALS and about whether their products are available via compassionate use or Right to Try. It further mentions that, as noted in the expanded access guidance, assessing serious adverse events in these programs must consider the context in which the treatment is provided.

“We want to reassure sponsors that providing a drug under expanded access very rarely impacts development timelines,” the FDA says.

“The FDA remains deeply committed to supporting the ALS community,” the statement reads, adding that the agency also “looks forward to continuing our dialogue with the ALS community, and is looking into how to proceed with additional meetings that will best facilitate this engagement.”

José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.
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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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11 comments

  1. MAX HORN says:

    HAVE THERE BEEN ANY TRAILS WITH STEM CELL INJECTIONS IN THE SPINE. I UNDERSTAND THAT IT WAS BEING DONE IN CANADA.WE ARE MOVING WAY TO SLOW TO MANY ROAD BLOCKS.
    RESPECTFULLY
    MAX HORN

    • Michelle Osuski says:

      I know that Mayo clinic in Minnesota is working on stem cell. I was told that when I was there in July. I was told that I was too old.

    • Becky says:

      My husband had them in Jerusalem 3 years ago under a compassionate care act. No longer available of course. Really don’t know if it helped because nothing to compare to. Has declined though in last year.

    • John Michael says:

      In the spine and intrathecaly are very different procedures. Intraspinal you may check with dr Svensson from cedar Sinai, the other dr glass from Emory failed. That leave brainstorm nurown in phase3

      • Terri S. Mieyal says:

        Why aren’t they discussing CuATSM? – a copper based compound being developed by Collaborative Medicinal Development, LLC which has already passed phase 1 safety trials in 32 humans, where it demonstrated the ability to slow als progression by as much as 70%. No phase 2 FDA trial has yet been announced, although due to the stellar results of the phase 1 safety trial this will happen sometime in 2019/2020…

  2. Randy says:

    The third stage of stem cell ended in July and now they say 1 year or more we have to wait for the results to come out. You see so many positive results, why so long of a wait???
    Time is not on the side of the patients with ALS.

    • Michelle Osuski says:

      Exactly my mom died of ALS over45 years ago. Now I have ALS and still waiting.I suppose it will be an astronomical cost also like cancer medication.

    • ronnie cooley says:

      Randy I agree with you 100. But I believe that the company’s that are involved in the development of a ALS drug is looking at the profit end of the deal. And the FDA is still dragging there feet on getting anything approved. And the patients and caregivers are the ones who are going to suffer. But thats my opinion. Take care and God bless all of the ALS patients and caregivers.

      • Terri Mieyal says:

        Why aren’t they discussing CuATSM? – a copper based compound being developed by Collaborative Medicinal Development, LLC which has already passed phase 1 safety trials in 32 humans, where it demonstrated the ability to slow als progression by as much as 70%. No phase 2 FDA trial has yet been announced, although due to the stellar results of the phase 1 safety trial this will happen sometime in 2019/2020…

  3. Cindy says:

    If you are interested in stem cell therapies search articles in Harvard’s Stem Cell Institute to familiarize yourself with what’s up and coming. Or follow progress in Brainstorms NUROWN clinical trial which is in phase 3 in this country. There is also a platform clinical trial coming in early 2020 which will involve 5 new treatments. Not stem cell. Search Healey Center for ALS at Massachusetts General Hospital. There will be around 50 plus trial sites around the country. Try to remain informed and hopeful. I am an ALS patient with symptoms that began 3 years ago. God bless us and our caregivers.

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