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FDA Releases Guidance on ALS Therapies

Man in wheelchair


23 Sept. 2019. The Food and Drug Administration issued its latest guidance to developers of new drugs and biologics for treating amyotrophic lateral sclerosis. A statement announcing the document is signed by FDA’s acting commissioner Ned Sharpless, as well as Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research and Peter Marks, director of the agency’s Center for Biologics Evaluation and Research.

Amyotrophic lateral sclerosis, or ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder where neurons or nerve cells controlling muscles in the body begin to waste away, and can no longer send or receive signals from the brain or spinal cord. As the nerve cells stop functioning, muscles in the limbs, and later speech and breathing muscles, begin weakening and eventually stop functioning. Most people with the disease die of respiratory failure. There are currently no cures for ALS, and few effective treatments for slowing progression of the disease.

The FDA statement notes that the “lack of new treatments for ALS is deeply frustrating for patients and caregivers.” The agency says its final guidance on ALS, provides industry “with the FDA’s current scientific thinking so that effective treatments with a favorable benefit to risk profile can be most efficiently developed, studied, and ultimately made available to patients.”

The guidance document spells out design factors to consider for clinical trials testing new ALS treatments. FDA urges developers of new therapies to limit exposure of patients to placebo groups, and to consider adopting master protocols for clinical trials that enable simultaneous of testing of multiple treatments with a common placebo group. The guidance also recommends use of adaptive clinical trials, with Bayesian statistics that allow for continuous recalculation of outcome probabilities as new data are added.

As reported by Science & Enterprise on 19 September, a clinical trial is beginning that uses an adaptive or platform design with a master protocol to test new ALS therapies. The trial, at Massachusetts General Hospital in Boston, is testing three new ALS treatments, with plans to soon add two more therapies.

The new guidance encourages more use of patient-reported outcomes in measuring the effectiveness of new ALS treatments, in addition to standard functional rating scales. These outcome measures can include objective measures, such as, muscle strength as well as more subjective quality-of-life indicators. However, the document advises that the need for patient-reported outcome data be balanced against the burden placed on ALS patients.

In addition, says the document, clinical trials testing ALS treatments should consider using exploratory biomarkers as outcome indicators. These surrogate or indirect outcome measures may help predict clinical benefits from therapies, and could support a request for accelerated approval of a new therapy. For safety assessments, FDA says it will accept data from across all stages of the disease, and from participants not included in efficacy tests of the new treatments. In general, says FDA, exposure by patients to new therapies for one year is considered adequate for approval of new drugs intended for chronic use in treating ALS.

The statement notes that ALS patients deserve the highest-quality therapies that undergo rigorous evaluations measured against high standards. At the same time, says the statement, “FDA has long stressed the appropriateness of exercising regulatory flexibility in applying the statutory standards to medical products for serious diseases with unmet medical needs, while preserving appropriate assurance that they are effective and have a favorable benefit to risk profile.” As a result, says FDA, the agency is willing to use its expedited development and approval programs to bring new treatments to ALS patients.

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