Shares of Lev Pharmaceuticals Inc. tumbled 33 percent after the FDA requested additional information - though likely no new trials - prior to an approval of Cinryze, the company's C1 inhibitor in hereditary angioedema.
In the approvable letter, the agency asked for further information regarding chemistry, manufacturing and controls, plus additional analyses of existing efficacy data from the company's two Phase III trials testing Cinryze as both an acute and a prophylactic treatment in HAE patients.
Despite prodding from analysts during the firm's conference call, Lev executives declined to disclose any specific details from the letter. CEO Joshua Schein said only that the FDA's questions were "reasonable" and that the company intended to provide "reasonable answers in a timely manner," with hopes of securing final product approval in mid-2008.
The delay in product launch, combined with the company's pointed disclaimer in its press release that it could offer "no assurances" that "additional clinical studies will not be requested," clearly left investors unsettled, and Lev's stock (OTC BB:LEVP), trading at 20 times its normal volume, fell 54 cents Thursday to close at $1.09.
The New York-based company submitted its biologics license application for Cinryze in late July and became the first firm to file for U.S. approval of a drug in HAE, a rare genetic disorder that affects about 10,000 people nationwide and causes recurrent and potentially life-threatening inflammatory attacks of the larynx, abdomen, face, extremities and urogenital tract.
Lev's drug has orphan status, which means its approval likely would preclude potential competitors Pharming Group NV and CSL Behring, both of which are in late-stage development with their respective C1 inhibitors, from entering the market until Cinryze's seven years of exclusivity expires.
King of Prussia, Pa.-based CSL's Berinert is the next closest to market, having met its endpoint successfully in a Phase III study in November. CSL is expected to file for regulatory approval this year in the U.S., Canada and Europe. Meanwhile, Pharming's Rhucin, a C1 inhibitor derived from the milk of transgenic rabbits, is finishing up Phase III testing.
Others crowding into the HAE space include companies with non-C1 inhibitor drugs, such as Jerini AG and Dyax Corp. In October, Berlin-based Jerini filed for approval of Icatibant, a synthetic peptidomimetic agent, and the company got a boost a few weeks ago when the FDA determined it was no longer necessary to hold a Feb. 20 advisory meeting and opted to allow Icatibant's application to proceed with priority review, with an April 26 PDUFA date.
Dyax, of Cambridge, Mass., is developing DX-88 (ecallantide), a recombinant plasma kallikrien inhibitor, which yielded positive results in a Phase III study last year. The company is conducting a confirmatory trial, with results expected this year. Pending positive data from that second trial, and assuming a six-month priority review process, Dyax has said DX-88 could gain approval as early as late 2008.
Because Icatibant and DX-88 each work via different mechanisms of action, those drugs likely would not be blocked from the market by orphan drug approval of a C1 inhibitor. But the drugs that make it through the approval process first would have an obvious advantage, since there are no approved treatments in the U.S. for HAE.
Lev's Schein said it was his company's policy not to comment on the competitive landscape, but he told investors that Cinryze's approvable letter and new timeline will not affect ongoing commercialization activities in preparation for the product's launch. The company also continues offering the drug to patients in two ongoing open-label studies, and those patients will be able to receive the drug on a compassionate-use basis prior to final approval.
The Cinryze BLA included data from its pivotal 71-patient CHANGE (C1-inhibitor in Hereditary Angioedema Nanofiltration Generation evaluating Efficacy) trial, in which the drug met its primary endpoint by statistically significantly reducing the time to relief of acute HAE symptoms. Lev amended the application in October to include data from a second Phase III study, in which Cinryze demonstrated efficacy as a prophylaxis in HAE patients. (See BioWorld Today, Aug. 1, 2007.)