Lev Pharmaceuticals released data to support use of its C1 inhibitor replacement therapy Cinryze to reduce the number of attacks suffered by hereditary angioedema patients at the American Academy of Allergy, Asthma and Immunology meeting in Philadelphia March 18.

The data, submitted to FDA in October as an amendment to the Cinryze BLA, is slated for review by FDA's Blood Products Advisory Committee May 2 (¹ Also see "Lev’s Cinryze To Get FDA Blood Products Advisory Committee Review" - Pink Sheet, 13 March, 2008.).

While Cinryze has first-to-market competition as a therapy for acute disease, it is the only product with Phase III data on prophylactic treatment of the ultra-orphan condition.

Patients receiving Cinryze experienced 52 percent fewer attacks (p<0.0001), the primary endpoint of the Phase III study. They also had a 66 percent reduction in days of swelling (p<0.0001) and decreases in the average severity of attacks (p=0.0008) and average duration of attacks (p=0004). No safety issues were identified.

The 24-week study enrolled 22 patients with a history of at least two attacks a month and randomized them to receive 12 weeks of either Cinryze or placebo, switching at the 12-week point. All patients were eligible to receive open-label Cinryze for acute attacks.

Patients with HAE experience swelling of the extremities, face, abdomen and urogenital tract, as well as life-threatening swelling of the larynx.

Cinryze's single-treatment alternative "will be a welcome option for both the prescribing physician and the affected patient," Rodman & Renshaw analyst Michael G. King said in a report from the allergy academy meeting.

Because "preventing an attack is preferable to waiting for an acute attack to manifest," the 10 percent to 20 percent of HAE patients who suffer from more than two attacks a week are likely candidates for prophylactic Cinryze, King reasons.

Orphan drug competition a cliffhanger

New York-based Lev submitted the BLA for acute treatment of HAE in July but received a "complete response" letter from FDA in January asking for additional chemistry, manufacturing and controls information, as well as additional analysis of efficacy data.

During the firm's March 13 year-end earnings call, Lev CEO Joshua Schein said the firm is on track to complete the resubmission by mid-second quarter. He said the firm continues to hope for a mid-year approval for Cinryze but acknowledged that an advisory committee hearing usually results in a six-month review.

Schein would not venture whether FDA might split out the acute and prophylactic indications or whether the firm could receive orphan drug status for only one or the other.

The first drug to market with an orphan drug indication gets seven years of market exclusivity.

"There are different scenarios that one can certainly envision here, and we're evaluating all of them," Schein said.

Meanwhile, CSL Behring, in Bern, Switzerland, and King of Prussia, Pa., submitted a BLA for its C1-inhibitor, C1-INH, March 6, asking marketing approval for treatment of acute attacks (² Also see "CSL Behring Submits C1-INH For Hereditary Angioedema" - Pink Sheet, 6 March, 2008.). C1-INH is marketed in Europe as Berinert .

Following this turn of events, "Behring could receive approval ahead of Lev and lock Cinryze out of the acute market," Susquehanna analyst Jason Kolbert said in a March 19 research note. However, Kolbert models sales in the prophylactic setting alone to peak at almost $150 million in 2013.

The wording of the orphan drug law "leaves room for interpretation as to orphan designation's application to a specific labeling for a disease (acute vs. prophylactic treatment), or for the disease itself," Kolbert writes. However, "Behring would be well within its rights to claim that the act pertains to all indications of a disease," he adds. "This would be a worst-case scenario."

Kolbert gives Cinryze a 15 percent chance to reach market in the acute setting and an 80 percent chance for commercialization in prophylaxis - if it is not blocked by approval of Berinert or of Pharming's candidate Rhucin , a recombinant C-1 inhibitor. Leiden, Netherlands-based Pharming has said it plans to file a BLA this year.

Non-C1 inhibitor replacement competitors for the HAE market, and orphan exclusion, include Cambridge, Mass.-based Dyax, which has DX-88 (ecallantide), a recombinant kallikrein inhibitor, in Phase III.

Berlin-based Jerini has an April 26 action date for Firazyr (icatibant), a bradykinin blocker with a checkered regulatory experience (³ Also see "Advisory Committee Review Of Firazyr Canceled" - Pink Sheet, 8 January, 2008.).

-Shirley Haley (s.haley@elsevier.com)

Lev Shows Cinryze Prophylactic Data

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