RARE Daily

Reata Warns of Possible Delays in Seeking Approval for Friedreich’s Ataxia Drug

August 11, 2020

Rare Daily Staff

Reata Pharmaceuticals warned that the U.S. Food and Drug Administration may require the company to conduct a second pivotal trial of its experimental Friedreich’s ataxia drug omaveloxolone before considering it for approval.

The news, contained in a release reporting its results for the second quarter of 2020, sent Reata’s shares falling by a third on Monday.

Friedreich’s ataxia (FA) a is progressive, neurodegenerative condition caused by mutations in the FXN gene. Signs and symptoms usually begin in puberty and lead to progressive impaired muscle coordination, gradual loss of muscle strength and sensation in the arms and legs, muscle stiffness, and impaired speech.

The company had planned to apply for approval of omaveloxolone following the positive results from its MOXIe Part 2 study in October 2019, subject to discussion with regulatory authorities.  Reata said that it recently completed a meeting with the FDA in which the agency said that it is not convinced that the MOXIe Part 2 study is adequate to support a single study approval without additional evidence and said in preliminary comments that it may need a second pivotal trial that confirms the results of the MOXIe Part 2 study with a similar magnitude of effect. The study used the modified Friedreich’s Ataxia Rating Scale (mFARS), a neurological exam that looks for signs that reflect areas affected in Friedreich’s ataxia.

In response to the preliminary comments, the Friedreich’s Ataxia Research Alliance, FA clinicians, and Reata provided the FDA with information to demonstrate that it will be difficult to conduct an additional, prospective clinical trial in FA because of the slow progression rate of FA, the limited number of FA patients available for clinical research, the small number of clinical trial investigators who can conduct the mFARS exam, and the impact of the COVID-19 pandemic on the ability to conduct neuroscience clinical trials. 

The company said conducting an additional pivotal study would result in a long delay in the availability of a potentially effective therapy to patients with a progressive, life-threatening disease with no treatment options. 

The FDA acknowledged the unmet need of patients with FA, reiterated its commitment to facilitate the development of omaveloxolone within the constraints of the regulatory standards, and emphasized its willingness to consider all available options to meet the regulatory standards.  The FDA also acknowledged that launching a new neuroscience clinical trial now may not be possible because of the COVID-19 pandemic.

At the meeting with the FDA, FARA, key opinion leaders, and Reata proposed a second study (the “crossover study”) to provide additional evidence of effectiveness. The study would measure the effect of omaveloxolone on mFARS in patients who were previously randomized to placebo in the MOXIe Part 2 study and are being treated with omaveloxolone in the MOXIe open-label extension study.  The FDA acknowledged that a study like the proposed crossover study could provide important additional information and asked the company to submit a design for the crossover study for their consideration.

Reata said if the FDA accepts the crossover study, it could complete it as early as the fourth quarter of 2020. If the FDA views the crossover study data as sufficiently positive to provide confirmatory evidence, the company said it will apply for approval of the drug during the first quarter of 2021. 

If the FDA rejects the proposal or if the data are not supportive, Reata said it would evaluate whether it is feasible to conduct a second pivotal study in FA patients as suggested by the FDA. 

The company said whatever happens with the FDA, it plans to pursue marketing approval outside of the United States.


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