Plant-based Gaucher's drug passes Phase III trial
This article was originally published in Scrip
Protalix Biotherapeutics' lead-drug candidate, Uplyso (taliglucerase alfa; formerly prGCD), was safe and effective in its pivotal Phase III trial, show top-line results. With these results, the company's Gaucher's disease therapy inches closer to becoming the first transgenicplant-produced drug to be approved for human use.
"We expect to complete the ongoing rolling new drug application submission for marketing clearance with FDA before the end of this year," said Dr David Aviezer, president and CEO of Protalix.
If approved, the Israeli company's product would compete with Genzyme's top-selling drug Cerezyme (imiglucerase), and potentially with Shire's late-stage drugcandidate velaglucerase alfa, which is still in Phase III trials. Both Protalix and Shire have benefited this year following viral contamination at one of Genzyme's manufacturing plants that caused the company to halt all production of its gold standard Gaucher's disease drug. Facing a shortage, the US FDA approved treatment protocols that have increased the availability of both Shire's and Protalix's as-yet-unapproved products (scripnews.com, August 19th, 2009).
Consequently, Protalix's share price has more than doubled since the viral contamination was announced in mid-June, and closed at $9.37 on Amex on October 15th.
Genzyme may face difficulties winning its patients back, and it has estimated that Cerezyme sales in 2009 will be $800 million, down from $1.2 billion last year.
Patients with Gaucher's disease, an inherited lysosomal storage disorder, lack the enzyme glucocerebrosidase. Consequently, glucocerebroside accumulates in a various organs, causing symptoms including enlarged spleen. Gaucher's is thought to affect 10,000-15,000 patients worldwide.
Cerezyme, as well as Uplyso and velaglucerase alfa, are recombinant forms of glucocerebrosidase, but they are produced in different ways. Uplyso is made in a slurry of carrot cells, Cerezyme is made in hamster cells, and velaglucerase alfa is made in a human cell line.
nine-month study
In Protalix's pivotal trial, 31 Gaucher's disease patients were randomised to receive either 30 or 60 units/kg of Uplyso every two weeks for nine months. Both doses met the primary endpoint, change from baseline in spleen volume as measured by MRI (p<0.0001). a="" significant="" change="" from="" baseline="" was="" observed="" after="" six="" months,="" the="" company="">
The high dose of drugalso induced significant improvements in haemoglobin level, liver size and platelet count, compared with baseline, all secondary endpoints.
The company reported that treatment was well-tolerated, with no serious adverse events. Notably, 6% of patients in the trial developed antibodies to the treatment, compared with 15% of patients who are treated with Cerezyme.
The company will present detailed results at an upcoming conference.
pharmers rejoice?
Biopharmaceutical researchers have been trying to turn plants into controllable drug factories for the past 20 years. These "pharmers" have argued that genetically engineered plants could provide cheaper drug production methods than conventional techniques. However, the field has faced numerous stumbling blocks, both scientific and regulatory.
Protalix has circumvented some of the unease– such as regulatory concerns that drugs grown in fields may be contaminated by dirt and bug remnants – by producing its drug in plant cells grown in sterile vats. As such, it is one of only a handful of drugs that has made its way through to clinical trials.
Companies with plant-made drugs in Phase II development include Biolex, whose Locteron (interferon alpha 2b) is produced in duckweed, and SemBioSys, whose SBS-1000 (insulin) is produced in safflower.
AnFDA approval for Protalix's Uplyso could help ease regulatory hurdles that have held up the field, thus potentially ending a "pharming" drought that has hindered the development of plant-based drugs.