Grünenthal's investigational non-opioid medicine, resiniferatoxin (RTX), has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of pain associated with osteoarthritis of the knee. This designation aims to accelerate the development and review of drugs intended to treat serious conditions where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies on clinically significant endpoints.
Clinical Development and Trial Design
Resiniferatoxin, a TRPV1 agonist also known as MTX-071, is currently undergoing a global Phase III clinical program to evaluate its efficacy and safety when administered via intra-articular injection in adults experiencing pain due to knee osteoarthritis. The Phase III program will be conducted across approximately 200 investigation sites, eventually enrolling around 1,800 patients, and should generate results in 2024, according to Grünenthal's chief scientific officer Jan Adams. The trials will recruit individuals with osteoarthritis who have exhausted other treatment options but continue to experience moderate to severe pain.
Mechanism of Action and Potential Benefits
Resiniferatoxin works by targeting the TRPV1 receptor, similar to capsaicin found in chili peppers, but with significantly greater potency. Phase 2 results demonstrated a long-lasting and significant pain-relieving effect, along with functional improvements compared to placebo, following injection of resiniferatoxin directly into the affected joint. Grünenthal hopes resiniferatoxin will offer a non-opioid treatment option that combines long-lasting pain relief with a functional improvement of the affected joints.
Osteoarthritis Burden and Unmet Needs
Knee osteoarthritis is a progressive condition affecting over 360 million people worldwide and may have severe symptoms, including pain. "More than 300 million patients suffer from osteoarthritis, a progressive disease that currently cannot be cured [and] they often experience debilitating pain as a result of their condition," said Adams. The company aims to bring resiniferatoxin to market in 2025, if all goes well.
Competitive Landscape
Development of TRPV1 agonists for pain isn’t a new concept, but many first-generation drugs were beset by safety issues – notably Amgen's AMG517 and Merck & Co's MK2295 – while AstraZeneca's candidate AZD1386 made it into phase 2 in osteoarthritis but failed to show efficacy. Among these still in development, Glenmark's orally active GRC17536 cleared a phase 2a study in diabetic neuropathy but has bioavailability issues that have held up a phase 3 programme. Johnson & Johnson meanwhile had a candidate called mavatrep (JNJ-39439335) in early clinical development, but it no longer appears in its pipeline listing.
