FDA Tell Protalix and Chiesi It won’t Grant Accelerated Approval for Fabry Therapy

Rare Daily Staff

The U.S. Food and Drug Administration notified Protalix BioTherapeutics and Chiesi Global Rare Diseases that it would not grant accelerated approval of pegunigalsidase alfa (PRX‑102) for the treatment of adult patients with Fabry disease.

The companies did not disclose the reason for the decision but said that it is studying the complete response letter from the FDA to determine what additional actions are required to obtain approval of PRX‑102.

“While disappointing, we remain confident in the strength of our data and in the depth of our program,” said Dror Bashan, Protalix’s president and CEO. “We remain committed to the program and to working with the FDA and Chiesi toward the approval of PRX‑102.”

Fabry disease is an X-linked inherited disease caused by deficient activity of the lysosomal α‑Galactosidase‑A enzyme, resulting in progressive accumulation of abnormal deposits of a fatty substance called globotriaosylceramide (Gb3) in the blood and blood vessel walls throughout the human body. Symptoms of Gb3 deposition range from episodes of pain, gastrointestinal (GI) symptoms, fatigue, angiokeratoma, and abnormal sweating, to serious complications including cardiovascular, renal, and cerebrovascular events.

Pegunigalsidase alfa (PRX‑102) is an experimental, plant cell culture-expressed, and chemically modified stabilized version of the recombinant alpha-Galactosidase-A enzyme. Protein sub-units are covalently bound via chemical cross-linking using short PEG moieties, resulting in a molecule with unique pharmacokinetic parameters. In clinical studies, PRX‑102 has been observed to have a circulatory half-life of approximately 80 hours. Protalix designed PRX‑102 to potentially address the continued unmet clinical need in Fabry patients.

The PRX-102 application was initially submitted under the accelerated approval pathway and was granted Priority Review by the FDA. Priority Review is granted to therapies that the FDA determines have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions. The submission for PRX‑102 included a comprehensive set of preclinical, clinical, and manufacturing data compiled from the completed phase 1/2 clinical trial of PRX‑102, including the related extension study succeeding the phase 1/2 clinical trial, interim clinical data from the phase 3 BRIDGE switch-over study and safety data from Protalix’s on-going clinical studies of PRX‑102 in patients receiving 1 mg/kg every other week.

The companies said they remain committed to the phase 3 clinical program which is progressing, and patients continue to receive PRX‑102 treatment in the ongoing BALANCE study sponsored by Protalix, and various long-term extension studies.

In addition, Chiesi is providing access to pegunigalsidase alfa through its Expanded Access Program for Fabry disease patients in the United States who cannot be adequately treated with currently available FDA-approved drugs. The EAP is open to patients with a clinical diagnosis of Fabry disease who, in the opinion of the treating physician, have no comparable or satisfactory alternative treatment options with currently available FDA-approved therapies for Fabry disease. Other eligibility criteria apply.

Photo: Dror Bashan, president and CEO of Protalix BioTherapeutics