Protalix BioTherapeutics & Chiesi Farmaceutici Announce Successful Pre-BLA Meeting 

Protalix BioTherapeutics, Inc. and its development and commercialization partner, Chiesi Farmaceutici S.p.A. recently announced that they have completed a successful Type B Pre-Biologics License Application (BLA) meeting with the US FDA regarding the Accelerated Approval pathway for pegunigalsidase alfa (PRX‑102) for the treatment of Fabry disease.

The company, together with Chiesi, met with the FDA on October 15 to discuss key information on pegunigalsidase alfa to be included in a proposed BLA filing under the Accelerated Approval pathway. The company and Chiesi report that they have reached alignment with the FDA on the Accelerated Approval pathway for pegunigalsidase alfa. The BLA, as expected to be submitted to the FDA, will include data from the company’s completed Phase I/II clinical trials of pegunigalsidase alfa and from its ongoing Phase III BRIDGE clinical trial.

“The confirmation by the FDA regarding the proposed BLA submission, together with the finalization of the BALANCE study enrollment (78 patients) and the very promising interim results from the BRIDGE study, are three recent significant consecutive milestones achieved with respect to our Fabry late-stage clinical program,” said Dror Bashan, Protalix’s President and Chief Executive Officer. “We are committed to the completion of this program with positive results for the benefit of the Fabry patient community.”

The company and Chiesi also announced that they have reached an agreement with the FDA regarding the ongoing BALANCE study, as currently designed, serving as the confirmatory trial for PRX‑102. A confirmatory trial is required to convert a BLA approved under Accelerated Approval into a traditional approval.

The company and Chiesi expect to submit the BLA to the FDA by April of 2020. The FDA indicated that the nonclinical data, the clinical data, the safety database and manufacturing data are sufficient to support the BLA submission, and that no additional clinical trials will be required for the proposed BLA submission. The company and Chiesi expect that the fully electronic BLA submission will include a comprehensive set of preclinical, clinical and manufacturing related information on pegunigalsidase alfa. If approved, the company will be eligible to receive a milestone payment from Chiesi.

“We have now had three successful interactions with the FDA during 2019, which built on our long-term relationship with the Agency and made our regulatory path forward for pegunigalsidase alfa clear,” said Dr. Einat Almon, Protalix’s Senior Vice President, Product Development. “We expect that alignment with the FDA on the Accelerated Approval pathway for pegunigalsidase alfa results in our being significantly closer to bringing an approved product to market to help Fabry patients. Together with our partner Chiesi, we look forward to completing the application process, as well as continuing with our double-blind head-to-head phase III BALANCE clinical trial, which we feel will further strengthen the position of pegunigalsidase alfa within the Fabry patient community.”

Fabry disease is an X-linked inherited disease that results from deficient activity of the lysosomal enzyme alpha galactosidase A 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. Fabry patients inherit a deficiency of the enzyme alpha-galactosidase-A, 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.

The company’s proprietary pegunigalsidase alfa is an investigational, 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, pegunigalsidase alfa has been observed to have a circulatory half-life of approximately 80 hours. The company designed pegunigalsidase alfa to potentially address the continued unmet clinical need in Fabry patients of continuous disease progression, infusion reactions and immunogenicity.

Based in Parma, Italy, Chiesi Farmaceutici is an international research-oriented group with over 80 years’ experience in the pharmaceutical sector and is present in 28 countries. The Group researches, develops and commercializes innovative medicines in respiratory disease, special care and rare disease therapeutic areas. The Group’s Research & Development center is integrated with six other important research and development groups in France, the USA, the UK and Sweden, to promote its pre-clinical, clinical and registration programs. The Group employs around 5,700 people. Chiesi Group is a certified B Corp. For more information, visit

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 a 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 pipeline consists of proprietary, potentially clinically superior versions of recombinant therapeutic proteins that target established pharmaceutical markets.

Protalix’s first product manufactured by ProCellEx, taliglucerase alfa, was approved for marketing by the US 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 includes the following product candidates: pegunigalsidase alfa, a modified version of the recombinant human alpha-GAL-A protein for the treatment of Fabry disease, in phase III clinical trials (BALANCE, BRIDGE and BRIGHT studies); OPRX‑106, an orally delivered anti-inflammatory treatment, and alidornase alfa, both in phase II clinical trials. 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.