AnaMar Phase 2a study of AMAP102 misses mark but underscores potential

GOTHENBURG, Sweden—AnaMar AB, a Swedish biopharmaceutical company focusing on selective peripheral 5-HT receptor antagonists for debilitating and life-threatening diseases, has announced top-line results from an exploratory Phase 2a double-blind, placebo-controlled, parallel-group, randomized study evaluating the efficacy, safety and tolerability of AMAP102 for the treatment of inflammatory pain in 116 patients suffering from mild to moderate osteoarthritis (OA) of the knee, either with or without hand OA.

In the reported exploratory Phase 2a trial, AMAP102, a 5-HT2B receptor antagonist, was well tolerated with no reported serious adverse events, but fell short of demonstrating a statistically significant reduction in pain over a 28-day period compared to placebo, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC®) pain subscale.

However, preliminary results from subgroup analyses indicate potential efficacy in patients with higher levels of inflammation. Ongoing analyses are expected to confirm these early and encouraging findings, the company said in the statement detailing the results. “We set up the Phase 2 study to assess efficacy in patients suffering from pain,” says AnaMar CEO Owe Gårlin, “both knee and hand. Knee pain among patients tends to be sporadic while hand osteoarthritis is more constant. Halfway through the study we dropped hand-pain patients to focus on knee OA. Among this knee cohort results were disappointing so we again went back to hand OA, plus some knee OA. We need to reanalyze the data.”

Leif E. Dahlberg, Ph.D., professor of orthopedics at Lund University in Sweden, stated, “We look forward to receiving the individual patient data and final subgroup analyses from this exploratory Phase 2a trial, which will be reported before year end. AMAP102 has demonstrated significant disease inhibition and tissue protection in arthritis animal models, and reduction of IL-6, TNF-α and other inflammatory mediators in relevant human and animal in-vitro models. It therefore remains a viable candidate for continued clinical testing as there is much need for disease-modifying osteoarthritis drugs.”

AnaMar’s unique therapeutic pipeline originates from its proprietary research platform built over 15 years of sustained investment and in close collaboration with university research centers. The platform is focused on peripheral serotonin-related inflammatory diseases and life-threatening fibrotic conditions. Serotonin (5-hydroxytryptamine or 5-HT) is a signaling molecule best known for its role as a CNS neurotransmitter. However, most 5-HT release is found in the periphery, where it is involved in cardiovascular function, wound healing, and intestinal peristalsis. In pathological situations, peripheral 5-HT release exacerbates inflammatory processes and contributes to edema and the sensation of pain (and pruritus in inflammatory skin conditions), as well as fibrosis due to the proliferation of fibroblasts associated with chronic inflammation and tissue damage.

Gårlin added, “Overall, the study’s results lend further support for AnaMar’s peripheral 5-HT receptor targeting platform and 5-HT2B receptor antagonist therapeutic pipeline focused on multiple indications with significant medical need, including osteoarthritis, rheumatoid arthritis, atopic dermatitis and fibrosis.”

Osteoarthritis is the most common form of arthritis, affecting more than 150 million globally, and with more than 27 million adults having reported being clinically diagnosed with OA in the U.S. OA is a leading cause of joint pain and physical disability in working age adults and elderly retirees, and the number of sufferers continues to grow steadily due to the aging population and increased incidence of obesity.

A second drug based on the AnaMar platform is scheduled to begin clinical testing before year end. The Phase 1b/2a placebo-controlled, topical SAD/MAD, safety, tolerability and PK/PD study will investigate AM1030-CREAM, containing a novel 5-HT2B receptor antagonist specifically selected by AnaMar based on its cytokine reduction profile and anti-inflammatory properties, suppression of inflammation and itching in atopic dermatitis patients. Having already received ethics committee approval, this study is now awaiting final regulatory clearance.

Gunilla Ekström, AnaMar’s vice president of R&D, notes that both AMAP102 and AM1030-CREAM are patent protected by two different patent applications due to different binding patterns to secondary receptors. “AM1030 has a short half-life ,” she observes, “so is not an oral product, but works by the same mechanism.” The active ingredient is provided in a proprietary cream for daily use.

AnaMar is actively seeking and currently evaluating potential partnerships to help leverage and maximize its proprietary peripheral 5-HT receptor platform and accelerate the development and commercialization of its proprietary pipeline of high-potential 5-HT2B receptor antagonist therapeutic candidates.

AnaMar’s lead 5-HT2B receptor antagonist, AMAP102, is an orally bioavailable small molecule in early Phase 2a exploratory development for inflammatory pain in osteoarthritis. AMAP102 demonstrates disease inhibition and tissue protection in arthritis animal models, and reduction of IL-6, TNF-α and other inflammatory mediators in relevant human and animal in-vitro models. AMAP102 inhibits inflammatory mediated pain in relevant animal models and has successfully completed Phase 1 clinical testing without any serious adverse events or clinically relevant safety issues.