Gaucher disease, a hereditary, genetic disorder with severe and debilitating symptoms, is the most prevalent lysosomal storage disorder in humans. Lysosomes are small membrane-bound cellular structures within cells that contain enzymes necessary for intracellular digestion. Gaucher disease is caused by mutations or deficiencies in the gene encoding GCD, a lysosomal enzyme that catalyzes the degradation of the fatty substrate, glucosylceramide (GlcCer). The normal degradation products of GlcCer are glucose and ceramide, which are easily excreted by the cells through normal biological processes. Patients with Gaucher disease lack or otherwise have dysfunctional GCD and, accordingly, are not able to break down GlcCer. The absence of an active GCD enzyme leads to the accumulation of GlcCer in lysosomes of certain white blood cells called macrophages. Macrophages affected by the disease become highly enlarged due to the accumulation of GlcCer and are referred to as "Gaucher cells". Gaucher cells accumulate in the spleen, liver, lungs, bone marrow and brain. Signs and symptoms of Gaucher disease may include enlarged liver and spleen, abnormally low levels of red blood cells and platelets and skeletal complications.
Treatment of Gaucher Disease:
The standard of care for Gaucher disease is enzyme replacement therapy using recombinant GCD to replace the mutated or deficient natural GCD enzyme. The latest studies estimate that there are approximately 10,000 patients suffering from Gaucher disease worldwide. The current treatment for Gaucher disease, an enzyme replacement therapy, was used to treat over 5,200 patients in 2008, at an average annual cost of approximately $250,000 per patient. As enzyme replacement therapy does not cure the genetic disorder, but rather provides an external source for transfusion of the missing or mutated enzyme, Gaucher disease patients generally receive the treatment over their entire lifetime.
The Protalix Solution:
taliglucerase alfa (previous scientific name prGCD), our lead proprietary product candidate, is a plant cell expressed recombinant Glucocerebrosidase enzyme (GCD) for the treatment of Gaucher disease. We have successfully completed our pivotal phase III trial in September 2009. The Phase III clinical trial for taliglucerase alfa was a nine month, randomized, double-blind, parallel group, dose-ranging safety and efficacy study in patients with Gaucher disease. The trial met its primary endpoint, mean reduction in spleen volume after nine months compared with baselines, in both 60 U/kg dose and in the lower 30 U/kg dose treatment groups (P<0.0001). The primary endpoint was stipulated in the Special Protocol Assessment (SPA) agreed on by the Company and the U.S Food and Drug Administration (the “FDA”) prior to the commencement of the trial. Additionally, the primary endpoint was observed already after six months of treatment in both treatment groups. Statistically significant improvements compared with baselines were also observed in the secondary endpoints, including increase in hemoglobin level, decrease in liver size and increase in platelet count at the 60 U/kg dose. Statistically significant improvements compared with baselines were observed in hemoglobin level and liver size and significant nominal reduction in platelet count in the lower dose of 30 U/kg. The safety analysis for both doses showed that taliglucerase alfa was well tolerated and no serious adverse events were reported. Only 6% of patients in the trial developed antibodies to taliglucerase alfa during the study. None of the patients in the trial developed neutralizing antibodies to taliglucerase alfa . Only 6% of the patients in the trial experienced hypersensitivity. Most adverse events were mild in intensity and not drug related and were transient in nature. The Company plans to present more comprehensive results in the near future, and at upcoming medical meetings. The FDA granted taliglucerase alfa orphan product designation and fast track development status and was developed under a Special Protocol Assessment (SPA). We anticipate ending our rolling submition of a New Drug Application (NDA) for taliglucerase alfa to the FDA and other comparable regulatory agencies in other countries in the fourth quarter of 2009. In addition, we are conducting a Switch Over study to assess the safety and efficacy of taliglucerase alfa (previous scientific name prGCD). The trial was originally designed to include 15 patients with Gaucher disease that are currently undergoing enzyme replacement therapy with imiglucerase (Cerezyme®), Such trial was amended to include additional patients. Patients with stable disease will be switched from intravenous taliglucerase alfa every two weeks for a nine-month period. The taliglucerase alfa dose administered to each patient will be equal to the patient's previous imiglucerase dose and the infusions will be administered at selected investigational sites.The switchover-study is not a prerequisite for approval of imiglucerase treatment every two weeks to intravenous infusions of taliglucerase alfa every two weeks for a nine-month period. The taliglucerase alfa dose administered to each patient will be equal to the patient's previous imiglucerase dose and the infusions will be administered at selected investigational sites.The switchover-study is not a prerequisite for approval of taliglucerase alfa . At the end of the nine-month treatment period, all eligible patients from both trials will be offered the opportunity to enroll in the Company's on-going extension study. In addition, the Company is currently making taliglucerase alfa available to Gaucher disease patients in the U.S. and other countries under an Expanded Access Program approved by the FDA In previous clinical trials in healthy subjects and in vivo primate studies, taliglucerase alfa has demonstrated an increased half-life and prolonged presence of the enzyme in the blood serum of the subjects as compared to Cerezyme, the only enzyme replacement therapy currently marketed to treat Gaucher disease. We believe that taliglucerase alfa (previous scientific name prGCD), if approved, has the potential to offer patients and healthcare payers a more effective and cost efficient treatment of Gaucher.