The companies indicated they are studying the CRL to determine the best way to understand the problems and what course of action they might take.
Protalix Biotherapeutics and Chiesi Global Rare Diseases announced the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for their Biologics License Application (BLA) for pegunigalsidase alfa (PRX-102) for adults with Fabry disease. The application was for accelerated approval.
The companies indicated they are studying the CRL to determine the best way to understand the problems and what course of action they might take.
Fabry disease is an X-linked inherited disorder. It is caused by insufficient activity of the lysosomal alpha-Galactosidase-A enzyme. This results in progressive accumulation of abnormal deposits of globotriaosylceramide (Gb3), a kind of fatty substance. It accumulates in the blood and blood vessel walls. Symptoms include pain, gastrointestinal symptoms, fatigue, angiokeratoma (dark spots on the skin caused by dilation of capillaries), abnormal sweating as well as serious problems such as cardiovascular, renal, and cerebrovascular events.
PRX-102 was initially submitted under the accelerated approval pathway and received the FDA’s Priority Review designation. The submission included full preclinical, clinical and manufacturing data based on completed Phase I/II clinical trials and an extension study after the Phase I/II trial, interim data from the Phase III BRIDGE switch-over trial and safety data in ongoing studies.
PRX-102 is a plant cell culture-expressed and chemically modified stabilized form of the recombinant alpha-Galactosidase-A enzyme. In clinical trials, it was shown to have a circulatory half-life of about 80 hours.
“Based on extensive clinical data including results from the Phase III BRIDGE clinical trial of PRX-102 for the proposed treatment of Fabry disease, we continue to feel strongly that PRX-102 is an important option for the treatment of Fabry disease in adult patients, and we are continuing with our efforts to make this therapy available to patients,” said Giacomo Chiese, head of Chiesi Global Rare Diseases. “We thank the patients and clinicians participating in our completed and ongoing clinical studies evaluating PRX-102. We are continuing to coordinate closely with the FDA to address and quickly resolve the deficiencies contained in the CRL.”
On February 23, 2021, the two companies announced positive topline data from the BRIGHT Phase III trial of PRX-102, 2 mg/kg, administered every four weeks, for Fabry disease. The study was to evaluate the safety, efficacy and pharmacokinetics of the treatment in up to 30 patients with Fabry disease who had received previous enzyme replacement therapy, either Replagal (agalsidase alfa) or Fabrazyme (agalsidase beta).
Topline data indicated the 2 mg/kg IV infusion every four was well-tolerated and the patients maintained stable clinical status. No new patients showed signs of treatment-induced anti-drug antibodies after the change to treatment with PRX-102.
The study enrolled 30 adults, 24 males and 6 females. The most common disease symptoms were acroparesthesia, which is tingling, prickling, burning or numbness in the hands or feet; intolerance to heat; angiokeratomas; and hypohidrosis, or decreased sweating, which can result in heatstroke.
“While disappointing,” said Dror Bashan, Protalix’s president and chief executive officer, of the CRL, “we remain confident in the strength of our data and in the depth of our program. We remain committed to the program and to working with the FDA and Chiesi toward the approval of PRX-102.”
