Lev Pharmaceuticals’ Hereditary Angioedema Therapy Cinryze Could Reach Market In Early 2008

Second-generation C1 inhibitor has “tremendous body of safety and efficacy data” behind it from decades of use in Europe, CEO tells “The Pink Sheet” DAILY.

Lev Pharmaceuticals submitted a BLA for its C1-esterase inhibitor Cinryze for the acute treatment of hereditary angioedema, the company announced July 31.

The New York firm is the first to submit a U.S. marketing application for treatment of acute HAE. Lev asked for a priority review based on the ultra-orphan drug's potential as a lifesaving therapy, CEO Joshua D. Schein said in an interview with "The Pink Sheet" DAILY.

If Lev's application clears FDA without any setbacks, the company will enjoy a significant competitive advantage over competitors with Phase III therapies that could file a BLA or NDA in the interim. Under six-month review, Cinryze could reach the market in the first quarter of 2008.

"We do have potential competitors out there, but for the most part they're developing new chemical entities or novel compounds, which while scientifically elegant are really unproven in the clinical setting. So, we started this with a bit of an advantage because we do have this tremendous body of safety and efficacy data behind us," Schein said.

ZLB Behring is developing a C1 inhibitor for HAE, as is the Pharming Group, which is working on rhC1INH, a recombinant product (¹ (Also see "Pharming Submits Human Recombinant C1 Inhibitor To EMEA" - Pink Sheet, 21 Jul, 2006.)). Dyax's DX-88 (ecallantide) is a small molecule kallikrein inhibitor. In April, the company launched a confirmatory study at FDA's request and said it anticipates approval in late 2008 (² (Also see "Dyax Launches Confirmatory DX-88 Study Requested By FDA" - Pink Sheet, 17 Apr, 2007.)). Jerini AG, which also has a small molecule candidate, has said it plans to submit an NDA in the third quarter for its bradykinin antagonist icatibant.

Lev signed an exclusive agreement with Sanquin Blood Supply Foundation in the Netherlands "about three and a half years ago" for the manufacture of a C1 inhibitor, Schein said. Sanquin has been manufacturing a C1 inhibitor branded as Cetor since the early 1970s, and Cinryze, which is a nanofiltered product, "really represents the next generation of the Sanquin product," he explained.

Lev is assembling a commercialization team to support Cinryze upon approval, Schein said. "We have all the functional areas in place: marketing, distribution, reimbursement, patient services, and really the team is professionally complete but for the actual sales reps, who won't be hired until we receive licensure from the FDA."

In March, Lev announced positive results for Cinryze in the Phase III CHANGE trials (C1-inhibitor in Hereditary Angioedema Nanofiltration Generation evaluating Efficacy) for acute HAE, indicating a clinically and statistically significant reduction in time to relief of acute HAE symptoms.

A second portion of the CHANGE trial, testing the therapy in the prophylactic setting, has completed treatment, and results are expected in the second half. Lev has said it will submit those results as either a label expansion or an amendment to the current BLA.

HAE is a genetic disorder characterized by recurrent attacks of inflammation affecting the hands, feet, face, abdomen, urogenital tract and larynx, in which case it can be life threatening. In the acute CHANGE trial, the drug was evaluated against placebo in 71 patients experiencing attacks in the face, abdomen or genitals and administered on an open-label basis in another 21 patients experiencing laryngeal attacks.

Median time to sustained symptom relief was two hours for patients receiving C1-INH versus more than four hours, the maximum evaluation period for placebo (p=0.026). For laryngeal attacks, all 21 patients were successfully treated, the company said. In all, "more than 400 acute treatments of C1-INH have been administered in all parts of the CHANGE trials with no drug-related serious adverse events, no immunogenicity and no reports of injection site reactions," Lev said.

Schein predicted that the yearly cost for Lev's HAE would be comparable to the yearly costs associated with hemophilia therapies, at around $250,000. Cinryze is given intravenously with a 10 cc syringe and a butterfly needle, "very similar to the way hemophiliacs administer clotting factors, so patients in Europe do self-administer C1 inhibitor, and we envision it being used the same way in the U.S.," he said.

The market is estimated at about 10,000 HAE patients in the U.S., about 1,000 of them candidates for prophylactic therapy, Schein said.

Lev is investigating Cinryze as a potential therapy for other inflammatory indications, such as myocardial infarction, burn injury, septicemia and bone marrow transplantation. "Once we receive approval for hereditary angioedema, then we certainly intend to explore a number of these other potential applications for Cinryze either internally or through corporate partnerships," he said.

- Shirley Haley ([email protected])