Protalix BioTherapeutics & Chiesi Global Rare Diseases Announce US FDA Acceptance of Biologics License Application 

Protalix BioTherapeutics, Inc. together with its development and commercialization partner Chiesi Global Rare Diseases recently announced the US FDA has accepted the Biologics License Application (BLA) and granted Priority Review designation for pegunigalsidase alfa for the proposed treatment of adult patients with Fabry disease. The BLA was submitted via the FDA’s Accelerated Approval pathway. Pegunigalsidase alfa is the company’s purposefully designed, long-acting recombinant, PEGylated, cross-linked α-galactosidase-A investigational product candidate. The FDA set an action date of January 27, 2021, under the Prescription Drug User Fee Act (PDUFA). The FDA also indicated in the BLA filing communication letter that it is not currently planning to hold an advisory committee meeting to discuss the application.

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. This designation shortens the FDA review period following the acceptance of the BLA to six months compared to 10 months under standard review. Pegunigalsidase alfa was granted Fast Track designation by the FDA in January 2018.

The BLA submission includes a comprehensive set of preclinical, clinical and manufacturing data compiled from the company’s completed Phase 1/2 clinical trial of pegunigalsidase alfa, 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 the company’s on-going clinical studies of PRX–102 in patients receiving 1 mg/kg every other week.

“The FDA’s acceptance of the BLA and grant of priority review for PRX-102 are significant achievements for Protalix and Chiesi, and represent a crucial step forward as we look to establish a new treatment option to the Fabry patient community,” said Dror Bashan, Protalix’s President and Chief Executive Officer. “Based on the encouraging results for PRX-102 we have seen to date, we are eager to continue discussions with the FDA and to continue our other development efforts for PRX-102, as marketing approval of PRX-102 is our top priority.”

“PRX-102 represents an important advance in research with the potential to deliver significant advantages to patients with Fabry disease,” said Giacomo Chiesi, Head of Global Rare Diseases. “We are very encouraged by the strong interest in this therapy among both patients and clinicians and we look forward to the prospect of making it available to patients around the world who can benefit from treatment.”

Fabry disease is an X-linked inherited disease that results from deficient activity of the lysosomal α–Galactosidase–A enzyme resulting in progressive accumulation of abnormal deposits of a fatty substance called globotriaosylceramide (Gb₃) in blood vessel walls throughout a person’s body. Fabry disease occurs in one person per 40,000 to 60,000. Fabry patients inherit a deficiency of the α–Galactosidase–A enzyme, which is normally responsible for the breakdown of Gb₃. The abnormal storage of Gb₃ increases with time and, accordingly, Gb₃ accumulates, primarily in the blood and in the blood vessel walls. The ultimate consequences of Gb₃ deposition range from episodes of pain and impaired peripheral sensation to end-organ failure – particularly of the kidneys, but also of the heart and the cerebrovascular system.

Pegunigalsidase alfa (PRX–102) is an investigational, plant cell culture-expressed, and chemically modified stabilized version of the recombinant α-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. The company designed PRX–102 to potentially address the continued unmet clinical need in Fabry patients.

Chiesi Global Rare Diseases is a business unit of the Chiesi Group established in February 2020 and focused on research and development of treatments for rare and ultra-rare disorders. The Global Rare Diseases unit works in collaboration with Chiesi Group to harness the full resources and capabilities of our global network to bring innovative new treatment options to people living with rare diseases, many of whom have limited or no treatments available. The unit is also a dedicated partner with global leaders in patient advocacy, research and patient care. For more information, visit www.chiesiglobalrarediseases.com.

Based in Parma, Italy, Chiesi Farmaceutici is an international research-focused healthcare group with 85 years of experience in the pharmaceutical industry and a global presence in 29 countries. Chiesi researches, develops, and markets innovative drugs in the respiratory therapeutics, specialist medicine, and rare disease areas. Its R&D organization is headquartered in Parma (Italy), and is integrated with R&D groups in France, the US, the UK, and Sweden to advance Chiesi’s preclinical, clinical, and registration programs. Chiesi employs nearly 6,000 people. Chiesi Group is a certified Benefit Corporation. For more information, visit www.chiesi.com.

Protalix is a biopharmaceutical company focused on the development and commercialization of recombinant therapeutic proteins expressed through its proprietary plant cell-based expression system, ProCellEx. Protalix was the first company to gain FDA approval of a protein produced through plant cell-based in suspension expression system. Protalix’s unique expression system represents a new method for developing recombinant proteins in an industrial-scale manner.

Protalix’s first product manufactured by ProCellEx, taliglucerase alfa, was approved for marketing by the FDA in May 2012 and, subsequently, by the regulatory authorities of other countries. Protalix has licensed to Pfizer Inc. the worldwide development and commercialization rights for taliglucerase alfa, excluding Brazil, where Protalix retains full rights.

Protalix’s development pipeline consists of proprietary versions of recombinant therapeutic proteins that target established pharmaceutical markets, including the following product candidates: pegunigalsidase alfa, a modified version of the recombinant human α–Galactosidase–A protein for the proposed treatment of Fabry disease; OPRX–106, an orally-delivered anti-inflammatory treatment; alidornase alfa for the treatment of Cystic Fibrosis; PRX–115, a plant cell-expressed recombinant PEGylated Uricase for the treatment of gout; and others. Protalix has partnered with Chiesi Farmaceutici S.p.A., both in the US and outside the US, for the development and commercialization of pegunigalsidase alfa.