FDA Widens Path for Rare-Disease Treatments With New Approval

Federal regulators approved a drug to treat a debilitating disease using data collected about patients over decades, creating an opening for researchers of other rare conditions who often struggle to prove their treatments work.

The Food and Drug Administration on Tuesday approved Reata Pharmaceuticals Inc.’s drug Skyclarys, or omaveloxolone, for treating the neurological disorder Friedreich’s ataxia in adults and adolescents age 16 and older.

The FDA last year said results from a single clinical trial didn’t sufficiently demonstrate the drug slows the progression of a disease that causes progressive damage to the spinal cord, muscle weakness, and movement problems and often kills people by age 35. Instead of running another trial, Reata submitted additional data including an analysis from a so-called natural history study that has continued to collect information about patients for more than two decades.

“Data created by patient communities can be regulatory grade,” said Annie Kennedy, chief of policy, advocacy and patient engagement at the EveryLife Foundation for Rare Diseases, a nonprofit advocacy group. “This approval is proof of that principle.”

Unlike clinical trials, natural history studies don’t test a drug. Instead, patients every year undergo a battery of tests to track how a disease is progressing. For its omaveloxolone analysis, the Reata investigators compared disease progression in patients who received the drug to people in the natural history study who were close matches based on factors including gender and age of diagnosis but didn’t take omaveloxolone.

The FDA typically requires results from two clinical trials demonstrating a drug’s efficacy to ensure positive results in one trial are replicable. But with rare conditions, finding enough patients to run two clinical trials can be daunting, said Jennifer Farmer, chief executive officer of the Friedreich’s Ataxia Research Alliance, which funds research on the disease, including the natural history study. Families of patients have raised about $1 million a year to fund the study, Ms. Farmer said.

Reata’s pivotal trial included 103 patients—drawn primarily from the approximately 22,000 people worldwide with the disorder, mainly in the U.S., Europe and Australia. Some traveled hundreds or more miles to reach trial sites. Not everyone interested in participating was eligible. Given the challenges, Ms. Farmer said, “You might not be able to do another trial at all.”

An analysis by Friedreich’s ataxia clinicians and Reata determined that people who received the drug and continued to take it over three years experienced an almost 55% reduction in the progression of the disease compared with people in the natural history study who didn’t receive the drug.

“The data collected in the natural history study were critical to showing the drug’s benefit,” said Reata CEO J. Warren Huff.

The company said it plans to charge $370,000 a year for the drug and that through insurance and a patient-assistance program, patients should be able to gain access.

The FDA has said it is willing to approve a drug based on results from one trial and “confirmatory evidence” the drug is effectiveThere isn’t always agreement between the FDA and rare-disease researchers and advocates on what constitutes sufficient evidence.

The FDA last year approved Amylyx Pharmaceutical Inc.’s Relyvrio therapy for treating amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig’s disease, after some staff questioned whether one trial was sufficient to show the drug works.

The FDA said it relied on Amylyx’s finding in the trial that the drug slowed disease progression and an additional analysis the company conducted involving the same patients. The analysis showed that people on the trial who continued taking the drug lived longer than expected.

The FDA has encouraged patient groups to start natural history studies. The FDA-funded Rare Disease Cures Accelerator-Data and Analytics Platform collects patient-data across many rare diseases, including from clinical trials and natural history studies.

The Friedreich’s Ataxia Research Alliance grew from the experience of Ron and Raychel Bartek and their son, Keith, who was diagnosed with the disease in 1997 and died in 2010 at the age of 24. When the couple learned there was no cure, they joined with others to form the advocacy group.

To figure out how to measure the disease’s progression, the group brought 14 patients to the National Institutes of Health in 1999 and had each examined by 10 doctors who treat Friedreich’s ataxia. Twelve of the patients returned 18 months later to undergo the same tests by the same 10 doctorsThe project became the start of a natural history study that includes information from over 1,300 patients in the U.S., said Mr. Bartek. An effort is under way to further expand it by combining U.S. and European natural history studies, he said.

“For many rare diseases,” said Dr. David Lynch, principal investigator of the natural history database and director of the Friedreich’s ataxia program at Children’s Hospital of Philadelphia, “natural history studies are a necessary step to getting to a treatment.”

Write to Amy Dockser Marcus at [email protected]