Assistant Managing Editor

As Dyax Corp. continues ramping up sales of hereditary angioedema (HAE) drug Kalbitor (ecallantide) in the U.S., the biotech is expanding the drug's reach into Japan thanks to a potential $106 million deal with CMIC Co. Ltd.

While most of that funding will come on the back end – Dyax is getting $4 million up front, with the remaining $102 million due for development and sales milestones – CMIC is taking on all costs for getting Kalbitor, also known as DX-88, through regulatory approval in Japan, where an estimated 4,000 people are affected by HAE, a rare, genetic disorder characterized by severe and often painful swelling.

CMIC also will purchase drug product from Dyax and will owe the Cambridge, Mass.-based biotech royalties in the 20 percent to 24 percent range for product sales in Japan.

The Japanese company should be able submit a regulatory application in Japan based on data generated to date by Dyax, including results from the positive EDEMA pivotal studies, with only one additional trial required: a small pharmacokinetics-focused study designed to make sure the drug behaves the same way in Japanese patients, said Ivana Magovčević-Liebisch, executive vice president of corporate development and general counsel for Dyax.

The fact that CMIC has its own CRO business will help complete that trial quickly. And, once approved, Kalbitor could find itself well positioned in Japan, which is a "very interesting market," Magovčević-Liebisch told BioWorld Today, particularly because "there hasn't been much awareness of HAE."

The only product currently available in Japan is Berinert, a C1 inhibitor from King of Prussia, Pa.-based CSL Behring. But that's a plasma-derived product, and doctors and patients in Japan have remained leery of plasma-based drugs in the wake of the late 1980s scandal that resulted in roughly 2,000 Japanese patients contracting HIV via contaminated blood products.

Dyax's Kalbitor is a recombinant plasma kallikrein inhibitor, which should make it a more acceptable treatment option, Magovčević-Liebisch said.

And CMIC has experience working with doctors and patients. "They're an ideal partner," she said, enumerating some of CMIC's previous orphan drug successes, such as getting Alexion Pharmaceuticals Inc.'s paroxysmal nocturnal hemoglobinuria drug Soliris (eculizumab) cleared by Japanese regulators in April.

Overall, "it's a very nice transaction and fits very nicely with our strategy," she added.

Dyax had always planned to keep rights to Kalbitor in the U.S., while partnering rights for the rest of the world. The firm had explored the possibility of signing a single ex-U.S. partner, but opted instead for a series of smaller, regional deals. "We talked to companies with worldwide reach," Magovčević-Liebisch said. But larger firms might have relegated Kalbitor to "priority number 10 on their list. We wanted to do [a deal] with a company that would be committed to the drug."

Plus, orphan drugs tend to require a large degree of patient and physician education, she added.

Dyax also has a deal giving Israeli rights to Neopharm Group, and, in June, it inked a partnership with Italian pharma Sigma-Tau SpA for Europe, North Africa, the Middle East and Russia. The Sigma-Tau deal included $2.5 million up front, $2.5 million in equity, the potential to earn more than $100 million in milestones and royalties equal to 41 percent of net sales should the product reach market. (See BioWorld Today, June 22, 2010.)

A European application was accepted in July. Full approval is anticipated in a 12-month to 18-month time frame.

In the U.S., Kalbitor became the third drug available for HAE patients.

In addition to Berinert, which is approved for acute HAE, it faces competition from potential off-label use of ViroPharma Inc.'s C1 inhibitor Cinryze, which hit the market first. but is only approved for prophylactic use. (See BioWorld Today, Oct. 14, 2008, and Dec. 3, 2009.)

Dyax is banking on Kalbitor's somewhat broader label – covering all the HAE symptoms, including the potentially deadly laryngeal attacks – to give it a leg up over Berinert, approved only for abdominal and facial HAE attacks. Its subcutaneous administration and nonplasma base also is an advantage, Magovčević-Liebisch noted.

Launched in February, Kalbitor is getting "good reception from physicians and patients," she said. At the end of June, 264 HAE patients had entered the Kalbitor Access System and, of those, 117 already had the drug placed. The number of patients with placed drug – treatment readily available in case of an HAE attack – increased significantly from the first quarter to the second quarter and "we're seeing a very nice ramp-up.

"We told the Street we were confident that we'd have 300 [patients with] placed drug by year-end," she said.

Dyax reported second-quarter sales of Kalbitor totaling $1.9 million. Through June 30, sales had reached $3.2 million.

Beyond its HAE deals, Dyax pulls in substantial funding by partnering its phage display technology. The firm has more than 70 licenses, which have translated into 17 clinical-stage candidates at present, including two late-stage compounds – a VEGFR2/KDR molecule and EGFR molecule – developed by ImClone Systems Inc. (now Eli Lilly and Co.) which could reach the market and start producing additional royalties for Dyax as early as 2013.

The company recorded about $20 million in revenue from its phage display partnerships in 2009, and Magovčević-Liebisch said a similar amount is expected for 2010.

Dyax, which posted a second-quarter net loss of $5.3 million, or 5 cents per share, had about $94.4 million in cash as of June 30.

The company's shares (NASDAQ:DYAX) closed at $2.37, up 2 cents Thursday.