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.”
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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.”