Dyax Readies HAE Therapy Kalbitor For Launch; Awareness Precedes Approval

Despite still awaiting FDA approval, Dyax is gearing up for the launch of its hereditary angioedema agent Kalbitor (ecallantide), focusing mainly on awareness and reimbursement issues.

While Dyax will not hire a sales force until FDA approval of Kalbitor, President and CEO Gustav Christensen said that the company is building the infrastructure needed for a successful launch. Steps along the way include hiring a select number of personnel in marketing, reimbursement, analytics and sales.

"We also appointed a corporate compliance officer, head medical science liaisons and national sales directors for the East and West, all crucial positions for comparing and implementing the commercial effort needed post-approval," Christensen said during the company's second quarter earnings call.

He said he envisions the overall U.S. sales and medical science support structure to be "a small, focused, field-based team," comprised of 22 medical science liaisons and commercial sales representatives.

Dyax's current marketing team, however, is getting things rolling already, concentrating on two critical aspects of the launch: generating greater awareness of HAE and taking steps to ensure patient access to Kalbitor once it's approved.

"We have been working closely with the HAE community, including the U.S. HAE Association, on creating resources to better equip patients and caregivers to manage their disease," said Christensen.

He added that plans are well under way for establishing a patient support program to ensure patients will have access to the drug around the clock.

Dyax First To Respond To "Complete Response"

Those challenges are typical of the potential downsides of possibly being a first-in-class product: The field is wide open, but you have to till it.

Dyax finds itself leading a five-way race to be the first FDA-approved therapy for acute treatment of HAE. Currently the only FDA-approved HAE therapy is ViroPharma's Cinryze (C1 esterase inhibitor [human]) - which is indicated for routine prophylaxis against angioedema attacks (¹ (Also see "ViroPharma Gets Good News And Bad News On Cinryze From FDA" - Pink Sheet, 4 Jun, 2009.)).

Kalbitor is a kallikrein inhibitor and its competition comes mainly from C1 esterase inhibitors, such as Cinryze, CSL Behring's Berinert and Pharming's Rhucin . The fifth candidate is Shire/Jerini's Firazyr (icatibant), a bradykinin antagonist.

On June 1, Dyax responded to an FDA "complete response" letter, which the agency accepted, granting the company a new PDUFA date of Dec. 1, 2009 (² (Also see "Dyax Receives “Complete Response” For HAE Drug; REMS Will Be Required" - Pink Sheet, 30 Mar, 2009.)). The letter, originally sent to Dyax March 25, 2009, requested submission of a Risk Evaluation and Mitigation Strategy and additional information with respect to the chemistry, manufacturing and controls section of the BLA.

ViroPharma also received a "complete response" letter from FDA, although not until June 4.

The agency requested that the company conduct an additional clinical trial "due to their opinion that the placebo-controlled trial submitted in support of the sBLA lacked robustness." FDA did not, however, have any safety concerns.

CSL Behring is in the same boat - it received a "complete response" letter Dec. 5 citing manufacturing and clinical issues.

Pharming has yet to enter the first round, but plans to submit the BLA for Rhucin in September. Pharming announced March 31 that it is conducting additional data analyses at FDA's behest and plans to meet with the agency in the second half prior to submitting the application.

Shire/Jerini received an FDA action letter in April of last year and is planning a confirmatory Phase III trial and will resubmit Firazyr after the study is complete (³ (Also see "Jerini’s Icatibant Falters in U.S., Wins In Europe" - Pink Sheet, 24 Apr, 2008.)).

In an attempt to differentiate itself and prove that the HAE market is not yet saturated, Christensen stressed that the market size is quite significant for acute attacks and that new data are continuously forthcoming.

According to European data, the average patient in treatment with C-1 treats about 18 attacks per year, and the patient population in the U.S., Dyax estimates, is 10,000 patients.

Onset Of Action Data

Dyax presented new data on Kalbitor from an integrated analysis of the two pivotal Phase III studies (EDEMA 3 and EDEMA 4) that demonstrated treatment with the drug provides clinically meaningful, rapid and sustained relief of symptoms in acute HAE attacks when compared to placebo.

The analysis, which included 143 unique patients treated with Kalbitor or placebo, showed statistically significant improvement in symptoms with Kalbitor at four hours after treatment and that the effect persisted throughout the 24-hour period of evaluation.

The analysis also demonstrated that Kalbitor was efficacious in treating all acute attack locations and was well-tolerated, with no treatment-related serious adverse events.

The findings were presented June 7, 2009, at the 28th European Asthma, Allergy and Clinical Immunology Congress in Warsaw.

Additionally, new data from EDEMA 4 presented in a poster discussion suggested that Kalbitor is able to stop progression of acute HAE attacks. The data showed that fewer patients experienced emerging HAE symptoms after treatment with Kalbitor than did placebo-treated patients.

"Clearly, we are very encouraged by some of the data we have achieved in our Phase III trials," Christensen said, specifically the drug's rapid onset of action, sustained duration of action and repeatability of action over time.

He added that there will be additional data on clinically relevant endpoints, such as how quickly Kalbitor works.

Dyax Seeking Partnerships Outside U.S..

Dyax is currently in discussions for HAE partnerships outside the U.S., and Christensen noted that several new parties have joined the talks.

Specifically, Christensen said Dyax is looking for a partner with specialty drug experience and the ability to immediately take advantage of commercial opportunities, including familiarity with the European regulatory environment.

"Our business strategy is unfolding well with two significant catalysts expected to take place over the second half of this year - the DX-88 partnership in angioedema outside of North America, and the U.S. approval of DX-88 for HAE attacks," said Christensen.

But Dyax already has some partners with which it is looking at Kalbitor for additional therapeutic uses, including reducing blood loss in surgery and treating retinal disease.

Cubist Pharmaceuticals is evaluating Kalbitor for the reduction of blood loss in on-pump cardiac surgery, and the company recently announced the first patients treated in the second of two Phase II trials.

The European trial, known as CONSERV-2, is investigating Kalbitor's effect in cardiac surgery for people who are at a high risk of bleeding. CONSERV-2 follows CONSERV-1, which began in the first quarter and is evaluating the safety and efficacy of three different doses versus placebo.

Fovea Pharmaceuticals is evaluating Kalbitor for the treatment of retinal collusion, or RVO-induced macular edema. Clinical development is scheduled to begin this year.

In addition, two investigator-sponsored angioedema studies are on track to begin by the year's end - a sponsor study in Cincinnati in ACE inhibitor- induced angioedema and a compassionate use program in acquired angioedema.

- Lauren Smith ([email protected])