Earlier this month, Protalix (PLX) released the long-anticipated results of its BALANCE study, which generated an immediate spike in its stock price. What I'm liking to see is that 10 days later, it's holding at about 30% over the previous, with healthy continuing volume and increasing interest from institutions and analysts. The study showed that, after procedural bumps in the road that allowed competitor Sanofi's Fibrazyme to be first to market, Protalix's pegunigalsidase alfa (PRX-102) can be equally effective, and should have a good opportunity to compete for market share in patients with Fabry disease.

The two-year randomized, double-blind, active-control study of PRX-102 in adult Fabry patients with deteriorating renal function was designed to evaluate the safety and efficacy of 1 mg/kg of PRX-102 administered every two weeks compared to agalsidase beta (Fabrazyme). PRX-102 "successfully met the primary endpoint on kidney function in the active control, noninferiority study vs. agalsidase beta."

PRX-102 is a novel, PEGylated enzyme replacement therapy (ERT) under development for the treatment of Fabry disease. As the company describes it, "PRX-102 (pegunigalsidase alfa) is an investigational, plant cell culture-expressed, and chemically modified stabilized version of the recombinant α-Galactosidase-A enzyme. Protein subunits 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." 

As Dr. Einat Brill Almon, Protalix’s Sr. Vice President and Chief  Development Officer, further explains, “We believe that this multi-year study demonstrates the potential for switching from agalsidase beta to PRX-102 in the treatment of patients with Fabry disease. The study met our pre-defined criteria for non-inferiority of the primary endpoint of kidney function in a head-to-head active comparison on both the Intent-to-Treat (ITT) and Per Protocol (PP)  analysis sets. These topline results show that PRX-102 was comparable to agalsidase beta in  controlling eGFR decline, which is a key measure of Fabry disease progression, and continues to  demonstrate a favorable tolerability profile for PRX-102."

Two years ago, PLX-102 missed out on accelerated approval due to largely bureaucratic hurdles that were thrown up by the pandemic. The silver lining, however, is that the BALANCE study, which was already ongoing, no longer had to prove superiority to Fibrazyme, but only "non-inferiority." Addressing the issue of eGFR (estimated glomerular filtration rate) - a measure of your kidneys' ability to filter toxins or waste from your blood - is a crucial component of the treatment of Fabry disease. Fabry disease sufferers are missing an enzyme that metabolizes certain kinds of fat, and serious kidney problems, even failure, are an unfortunate component of the disease. Current treatments do not reverse degeneration but control the decline.
 

Meeting the endpoints means that Protalix can apply for a BLA (biologics license application) in 2H2022, as scheduled. 

If you can't get too excited about "non-inferiority," consider these thoughts. First, Fabry patients deserve alternatives, as do we all. As Dr. David Warnock, M.D., Professor of Medicine (Emeritus) at the University of Alabama at Birmingham, elaborates, "these topline results also indicate that PRX-102 was well-tolerated and support the potential to switch to this novel, investigational ERT from a currently approved ERT. As a physician, I believe  having an alternative therapeutic option would be an important landmark, and, pending  regulatory approval, will potentially improve access of Fabry patients to ERT.”

Also, the market for the drug is not a static one, even though Fabry is a rare inherited disorder. According to BALANCE investigator Dr. Khan Nedd, chief medical officer, Infusion Associates, Grand Rapids, Michigan, "Given that Fabry disease runs in families, patients tend to be more knowledgeable of treatment developments than many other patient groups, making it easier for new drugs to gain market traction." Encouragement of earlier diagnosis can also expand the need for and use of therapies.

The company continues to anticipate that longer-range results will indicate advantages to its product, from fewer side effects to the need for fewer drug infustions. 

The study was conducted by Protalix together with its partner in development Chiesi Global Rare  Diseases, a business unit of Chiesi Farmaceutici S.p.A., an international research-focused healthcare Group (Chiesi Group). Giacomo Chiesi, head of Chiesi Global Rare Diseases, noted “These data are especially encouraging following our recent announcement of the positive final results from our Phase III BRIGHT study of PRX-102 in Fabry disease and bring us one step closer towards potential approval of PRX-102 and launch in several countries as a much-needed treatment option for patients. We believe the totality of the data observed suggests a favorable  benefit-risk profile for the treatment of adult patients with a confirmed diagnosis of Fabry disease and the data will be included in our planned PRX-102 BLA resubmission to the FDA.” 

BLA approval of PRX-102 will put a second sword in Protalix's armory. Protalix was the first company to gain U.S. Food and Drug Administration  (FDA) approval for a protein produced through its proprietary plant cell-based expression system, ProCellEx. Protalix’s first product manufactured by ProCellEx, taliglucerase alfa, was approved by the FDA in May 2012 and, subsequently, by the regulatory authorities of other countries. Taliglucerase alfa treats another genetically inherited disorder, Gaucher disease. Protalix has licensed Pfizer Inc. the worldwide development and commercialization rights for taliglucerase alfa, excluding Brazil, where Protalix retains full rights. Investors also expect that once PRX-102 has completed its regulatory process, the company will return more focus to its promising pipeline.

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