Horizon Therapeutics, Inc, (PALO ALTO, California), a privately-held, late-stage biopharmaceutical company is focusing on the development and commercialization of therapeutic treatments for mild-to-moderate pain management based on innovative combinations of approved pharmaceutical products that seek to improve safety, efficacy, and patient compliance. The company announced that it has reached agreement with the US FDA via a special protocol assessment (SPA) for the phase III trial program of HZT-501, its "GI-friendly" prescription nonsteroidal anti-inflammatory drug (NSAID) for mild-to-moderate pain relief. The SPA agreement indicates that if the trials successfully meet their primary endpoints, the data will provide support for an efficacy claim in a marketing application to the FDA. The phase III program will comprise two trials involving a total of 1200 patients with mild-to-moderate pain, including patients with osteoarthritis. The two trials are expected to begin patient enrollment in the first half of 2007.

HZT-501, the company's lead product candidate, is a proprietary formulation of ibuprofen, the world's most prescribed NSAID, combined with famotidine, the most potent H2 receptor antagonist, in a single pill. HZT-501 is specifically designed to provide pain relief while reducing stomach acidity during the peak time of risk for ulceration. In a randomized pilot clinical study, famotidine was demonstrated to significantly reduce the incidence of gastric and duodenal ulcers versus placebo when administered with NSAIDs. The study was a randomized, controlled trial including 285 arthritis patients. The primary endpoint was the measurement of the cumulative incidence of endoscopically diagnosed gastric and duodenal ulcers at 4, 12, and 24 weeks in patients treated with an NSAID alone versus those treated with NSAID plus a total daily dose of either 40 mg or 80 mg of famotidine. The cumulative incidence of gastric ulcers was 20% in the NSAID-alone group and 8% in the 40-mg BID (twice daily) famotidine plus NSAID group (P  = .03). The cumulative incidence of duodenal ulcers was 13% in the NSAID-alone group and 2% in the 40-mg BID famotidine plus NSAID group (P  = .01). There were also significantly lower rates of gastric and duodenal ulceration when analyzed separately and when combined (28% for the NSAID-alone group versus 11% for the 40-mg BID famotidine plus NSAID group [P  = .003]).

The phase III program will evaluate the efficacy and safety of HZT-501 with a primary endpoint of reduction in the risk of development of ibuprofen-associated upper gastrointestinal ulcers in patients who require the use of ibuprofen. The clinical trials, to be conducted in the US, will be multicenter, randomized, controlled, and blinded for up to 24 weeks of treatment, followed by a 4-week safety evaluation period.

The company also announced it raised $15 million through a Series B financing to advance HZT-501 into pivotal phase III clinical trials. Scale Venture Partners, formerly known as BA Venture Partners, led the round with Sutter Hill Ventures and Pequot Ventures also participating. The company completed a $6 million Series A round in October 2005 with the same syndicate of investors.

In addition to HZT-501, Horizon has a pipeline of follow-on pain combination products in earlier stages of development. In October 2006, Horizon filed an investigational new drug (IND) application with the US FDA for its second investigational product, HZT-602, a proprietary formulation of the world's second most prescribed NSAID (naproxen) combined with famotidine.

—A. Techman

 

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