Moving one step closer to introducing the first therapy for acute hereditary angioedema (HAE) in the U.S., Lev Pharmaceuticals Inc. reported that its C1 inhibitor met the primary endpoint in a pivotal Phase III study.
Pending a meeting with the FDA, the New York-based firm expects to submit a biologics license application in the second quarter and looks for an expedited six-month review by the agency. Lev's C1-esterase inhibitor (C1-INH) was granted orphan drug status, which could provide it with seven years of marketing exclusivity upon approval.
"We look forward to working closely with the FDA," Joshua Schein, Lev's CEO, told BioWorld Today. "Our priority is to get this to market as quickly as possible."
A genetic disorder caused by a deficiency of the plasma protein C1-INH, HAE is characterized by painful swelling affecting the face, urogenital tract, abdomen and larynx.
To date, there is no approved therapy in the U.S. for HAE, which affects an estimated 10,000 people.
"It's been terrible for the number of patients and the physicians trying to treat this disease," Schein said, particularly given the fact that C1 inhibitors have been available for HAE in Europe for about 30 years.
In fact, Lev gained North American rights to its C1-INH technology from Amsterdam, the Netherlands-based Sanquin Blood Supply Foundation, a not-for-profit group that has been supplying C1-INH to areas of Europe. The product, made from human plasma, is in development as both a treatment for acute HAE and as a prophylactic.
Results from Lev's double-blind CHANGE (C1-inhibitor in Hereditary Angioedema Nanofiltration Generation evaluating Efficacy) Phase III study show that C1-INH "clearly met the study protocol, defined as sustained symptom relief," Schein said.
A total of 71 patients were randomized to receive either C1-INH, administered intravenously, or placebo, and the primary endpoint was measured by subject-reported symptom relief at three consecutive 15-minute intervals following treatment.
Data showed that those given C1-INH had a median time to sustained symptom relief of two hours vs. greater than four hours in the placebo period. C1-INH was found to be effective across all attack sites, and in an open-label trial subset of patients suffering potentially life-threatening laryngeal HAE attacks, "21 of 21 patients responded" with C1-INH, Schein said.
Results also confirmed the safety profile seen in prior studies. No drug-related serious adverse events were seen, and there were no reports of injection-site reactions.
Lev is one of about a half-dozen companies working on late-stage candidates for HAE, most of which also have been granted orphan status.
Close behind Lev's C1-INH is Berlin-based Jerini AG's Icatibant, a subcutaneously administered synthetic peptidomimetic, which is partnered with Cranbury, N.J.-based Kos Pharmaceuticals Inc. (now part of Abbott Laboratories). Icatibant generated mixed results in two Phase III studies, but Jerini informed investors last month that it had meet with the FDA and planned to file a new drug application in the third quarter.
Cambridge, Mass.-based Dyax Corp. anticipates results shortly from its Phase III study of DX-88, a kallikrein blocker, though the firm was told by the FDA in September that an additional confirmatory trial would be needed for approval, pushing the anticipated launch of DX-88 to 2008.
Pharming Group, of Leiden, the Netherlands, also expects to complete Phase III studies this year of Rhucin, its recombinant human C1 inhibitor derived from the milk of transgenic rabbits. A marketing authorization application for Rhucin is under review in Europe. And ZLB Behring, of King of Prussia, Pa., is in Phase III studies of its C1 inhibitor, Berinert, a product it has sold in Europe for 20 years. (See BioWorld Today, Sept. 25, 2006.)
In addition to acute HAE attacks, Lev is studying its C1-INH in the prevention of HAE attacks in a second portion of the CHANGE trial. Designed as a crossover study, it involves patients severely affected with HAE who will receive twice-weekly injections of C1-INH or placebo. Results are expected in the third quarter, and pending a positive outcome, "we'll either file a separate BLA or amend the existing BLA," Schein said.
Upon approval, Lev would market the product on its own, and the company is building a marketing and sales team in preparation of the launch.
Beyond HAE, Schein said C1-INH is being investigated in acute myocardial infarction. Though it has not yet entered the clinic in that indication, there have been other studies indicating the product's effectiveness in MI.
"That's certainly part of our development plan," he said, adding that Lev also will look at other indications that "involve that same chemical pathway."
Shares of Lev (OTCBB:LEVP) gained 24 cents, or 14.7 percent, Wednesday to close at $1.87.