-- Efficacy data for FAST-2 meets primary endpoint, FAST-1 and FAST-2 combined analysis demonstrates a reduction in time to onset of symptom relief
-- Patients receiving Icatibant reported a median time to onset of symptom relief of 2.5 hours in FAST-1 (versus 4.6 hours with placebo) and 2 hours in FAST-2 (versus 12 hours with comparator)
-- Initial submission of a New Drug Application (NDA) with the US Food and Drug Administration (FDA) expected by year-end 2006, with potential launch in 2007
-- Kos collaboration partner Jerini plans to seek expedited review by FDA
Kos Pharmaceuticals, Inc. (Nasdaq:KOSP) announced today preliminary results from two pivotal Jerini AG (FSE: JI4) Phase III Icatibant clinical trials, FAST-1 and FAST-2 (For Angioedema Subcutaneous Treatment), for the subcutaneous treatment of hereditary angioedema (HAE), a debilitating and potentially life-threatening genetic disease. The primary study endpoint was met in FAST-2; and while it was not met in FAST-1, combined analysis of both studies showed a significant reduction in time to onset of symptom relief for patients receiving Icatibant versus those receiving placebo or comparator as measured by a visual analog scale (VAS). Initial application for regulatory approval with the FDA is anticipated in December 2006 and Jerini plans to seek an expedited review by the FDA.
Patients receiving Icatibant reported a median time to onset of symptom relief of 2.5 hours in FAST-1 as compared to a median time of 4.6 hours for those receiving placebo. A median time of 2 hours was reported by patients receiving Icatibant in FAST-2, as compared to 12 hours by those receiving the comparator, tranexamic acid. A total of 56 patients participated in FAST-1, a double-blind, placebo-controlled study conducted in the United States, Canada, Australia and Argentina. The FAST-2 trial treated a total of 74 patients at clinical sites in 10 European countries and in Israel in a double-blind study against the comparator, tranexamic acid. An aggregate of 231 open-label treatments were administered in both trials. The median time to first improvement, as reported by patients receiving Icatibant in the FAST-1 and FAST-2 studies, was consistent with Jerini's Phase II study results.
"The strength and consistency of these trial results demonstrate Icatibant's potential as a safe, effective and much needed therapy for hereditary angioedema," said Adrian Adams, President and CEO, Kos Pharmaceuticals. "We are pleased that, based on these results, Jerini will seek expedited reviews by the FDA and the European Medicine Evaluation Agency, keeping Icatibant on track for a potential 2007 launch. Icatibant is an exciting near-term opportunity for Kos, and is an excellent example of the continued success of our expanded specialty pharmaceutical business model that enhances our growing R&D pipeline through sound and synergistic corporate development and licensing activities."
The primary endpoint of FAST-2, as measured by a VAS, was met with a median time to onset of symptom relief of 2 hours for Icatibant versus 12 hours for tranexamic acid (p less than 0.001). Secondary endpoints entered in the analysis also showed statistically significant differences in favor of Icatibant. Time to onset of relief of key symptoms, as measured by a preset reduction in the VAS, was highly significant for skin swelling (p less than 0.001); skin pain (p=0.002), and abdominal pain (p=0.028). Median time to first improvement of symptoms as reported by patients was 0.8 hours for Icatibant versus 7.9 hours for tranexamic acid (p less than 0.001). Icatibant also showed an excellent safety profile.
In FAST-1, the primary endpoint in median time to onset of symptom relief was 2.5 hours for Icatibant versus 4.6 hours for placebo. Although relevant clinically, this difference did not reach statistical significance (p=0.131) due to an unexpectedly high response to placebo in patients with abdominal pain as analyzed by the VAS. In two subgroup analyses, the primary endpoint was met (p=0.025 and p=0.024), and further analyses are ongoing. Time to onset of relief of key symptoms, as measured by VAS, showed a statistically significant reduction for skin swelling (p=0.032) and skin pain (p=0.007), and a strong trend for reduction in abdominal pain (p=0.056). Median time to first improvement of symptoms, as reported by patients, was 0.8 hours for Icatibant versus 16.9 hours for placebo (p less than 0.001). Also in this study, Icatibant showed an excellent safety profile.
For the treatment of life-threatening laryngeal attacks, Icatibant showed a significant and clinically relevant reduction in time to symptom relief. A total of 11 laryngeal attacks were treated in the FAST-1 and FAST-2 trial controlled phase, with patients reporting a median time of 1 hour (FAST-2) and 0.6 hours (FAST-1) to symptom relief. Time to symptom relief as assessed by the physician was 0.7 hours (FAST-2) and 0.8 hours (FAST-1). An additional 19 laryngeal attacks were also successfully treated in the Open Label Extension phase of the trials.
Further response of Icatibant efficacy was demonstrated in the combined analysis of FAST-1 and FAST-2, with data meeting both the primary endpoint and all secondary endpoints entered into the analysis. Icatibant has shown an excellent safety profile in previous and ongoing trials sponsored by Jerini and Sanofi-Aventis, and has been administered to date in over 1300 subjects. The safety profile was confirmed in the FAST-1 and the FAST-2 studies. No drug-related, serious adverse events occurred. The most frequent adverse events were injection site reactions such as erythema, swelling, and occasional itching and pain. These symptoms were transient and resolved spontaneously.
Icatibant is a potent and specific peptidomimetic bradykinin B2 receptor antagonist developed by Jerini AG. HAE is a rare genetic disease that can be debilitating, painful and life-threatening and is characterized by recurrent local swelling at three main sites: subcutaneous tissue, the gastrointestinal tract, and the larynx. There are approximately 10,000 diagnosed HAE patients in the European Union and the US; however, the disease is believed to be significantly under diagnosed. Experts estimate the HAE patient population could be as high as 75,000. Icatibant has been granted orphan drug status and fast-track designation by the FDA. HAE is the first of several indications for which Icatibant offers a potential treatment and the partnership with Jerini allows for ongoing potential clinical development in other forms of angioedema, asthma, and liver cirrhosis.
Kos has exclusive development, marketing and distribution rights for Icatibant in North America. As a potential first-to-market therapy for HAE, Icatibant subcutaneous administration and excellent safety profile demonstrated in clinical studies to date, offer key advantages to patients. Kos anticipates Icatibant entering a potential $300 million market space in North America, with orphan drug status securing seven-year US market exclusivity upon approval. To support the anticipated 2007 launch, Kos has established a new, self-contained Allergy Business Unit that will encompass sales and marketing, medical education and commercial services functions.
Icatibant, a synthetic peptidomimetic, works by blocking the B2 receptor as an antagonist to the peptide-hormone bradykinin. Bradykinin has been shown to be elevated in HAE patients and responsible for edema formation during HAE attacks. Icatibant has been granted orphan drug status for the treatment of angioedema by the FDA and the European Medicines Agency, potentially securing, upon approval, market exclusivity for seven and ten years, respectively. In addition, the FDA has granted fast-track designation to Icatibant in the indication HAE. Icatibant's subcutaneous administration, along with its excellent safety profile demonstrated in clinical studies to date and one-year-stability at room temperature, all offer key benefits to HAE patients.
About Hereditary Angioedema (HAE)
Hereditary Angioedema (HAE) is a debilitating and potentially life-threatening genetic disease affecting between 1:10,000 and 1:50,000 individuals worldwide. The disease is characterized by unpredictable episodes of edema and swelling of the hands, feet, face, larynx and abdomen. Swelling of the larynx can result in suffocation. In addition, patients sometimes have bouts of excruciating abdominal pain, nausea, and vomiting that is caused by intestinal wall swelling. The disease is caused by a genetic defect, passed from parent to child.(1)
(1)United States Hereditary Angioedema Association. FAQs. Accessed June 1, 2006: http://www.hereditaryangioedema.com/pamphlet.html
About Kos Pharmaceuticals, Inc.
Kos Pharmaceuticals, Inc. is a fully integrated specialty pharmaceutical company engaged in developing, commercializing, manufacturing and marketing proprietary prescription products for the treatment of chronic diseases with a particular focus on the cardiovascular, metabolic and respiratory disease areas. The Company's principal product development strategy is to reformulate existing pharmaceutical products with large market potential to improve safety, efficacy, and patient compliance. Kos' strategy also includes making measured investments in new chemical entity research through in-house and sponsored research, scientific in-licensing and general corporate development activities. The Company currently markets Niaspan(R), Advicor(R), Azmacort(R), Cardizem(R)LA, Teveten(R) and Teveten(R)HCT. Kos has a strong and growing research and development pipeline including proprietary drug delivery technologies in solid-dose, inhalation and aerosol metered-dose device administration to help fuel sustained, organic sales growth into the future.
Certain statements in this press release, including statements relating to application for expedited review by the FDA and European Medicine Evaluation Agency, the potential for the patient population in the HAE therapeutic area being as high as 75,000, the number of indications for which Icatibant offers a potential treatment, the submission of the NDA for Icatibant to the FDA in 2006, and the potential introduction of Icatibant to the market in 2007, the potential for the HAE market space in North America to reach $300 million, the Company's strong and growing research and development pipeline and future sales growth are forward-looking and are subject to risks and uncertainties which may cause actual results to differ materially from those projected in a forward-looking statement. These risks and uncertainties include market acceptance of Icatibant, the protection afforded by the Company's patents and those related to its acquired and licensed products, the ability to build awareness for the Company's products, including Icatibant, within the medical community, the continuing growth of the cardiovascular, respiratory and allergy markets, the Company's ability to increase the size of its sales force and to attract and retain sales professionals, the Company's and its licensors' ability to achieve regulatory approvals for products under development, including Icatibant, and to successfully launch such products in a timely manner, the ability of third party suppliers to the Company continuing to be able to perform their supply obligations, the Company's ability to entered into additional new business development opportunities, the progress of the Company's research and development pipeline, the effect of conditions in the pharmaceutical industry and the economy in general, as well as certain other risks. A more detailed discussion of risks attendant to the forward-looking statements included in this press release are set forth in the "Forward-Looking Information: Certain Cautionary Statements" section of the Company's Annual Report on Form 10-K/A for the year ended December 31, 2005, filed with the Securities and Exchange Commission, and in other reports filed with the SEC. All information in this press release is as of September 21, 2006 and the Company undertakes no duty to update this information.