Melt Pharmaceuticals has announced positive topline results from its Phase 3 clinical trial evaluating MELT-300, a novel sublingual tablet for procedural sedation during cataract surgery. The study demonstrated that MELT-300, a combination of midazolam (3mg) and ketamine (50mg), achieved statistically superior sedation compared to both sublingual midazolam and placebo.
The Phase 3 trial, conducted across 13 clinical sites in the United States, enrolled over 530 patients undergoing cataract surgery. Participants were randomized in a 4:1:1 ratio to receive MELT-300, sublingual midazolam, or sublingual placebo. The primary endpoint was the proportion of patients achieving successful procedural sedation.
The results indicated that MELT-300 was significantly more effective than both sublingual midazolam (P=0.009) and placebo (P<0.001) in providing successful procedural sedation. Furthermore, the need for rescue sedation was nearly two-fold higher in the sublingual midazolam group compared to the MELT-300 group (P=0.003), highlighting the enhanced efficacy and reliability of MELT-300.
Safety Profile
The safety profile of MELT-300 was generally comparable to placebo, suggesting that the combination of midazolam and ketamine, delivered sublingually, is well-tolerated in this patient population. This is a significant finding, as it supports the potential of MELT-300 to replace current IV-based cataract surgery sedation protocols, which often involve the use of opioids.
Clinical Significance
"We are extremely excited with this robust topline data from our pivotal Phase 3 study," said Dr. Larry Dillaha, Chief Executive Officer of Melt. "These overwhelmingly positive results support our belief that MELT-300, if approved by the FDA, would be a safe and effective non-IV, non-opioid alternative to current IV-based cataract surgery sedation protocols, which generally involve the administration of opioids."
With the number of cataract surgeries performed annually in the U.S. expected to exceed 5 million, the availability of a non-IV, non-opioid sedation option like MELT-300 could significantly improve patient experience and reduce the risks associated with traditional sedation methods. The sublingual administration, utilizing Catalent’s Zydis® delivery technology, allows for rapid absorption of the active ingredients, dissolving in as little as 3 seconds.
Future Implications
Melt Pharmaceuticals intends to seek regulatory approval through the FDA’s 505(b)(2) regulatory pathway. The company believes that the Phase 3 data, along with previous Phase 2 results, position them well to elevate the procedural sedation standard of care for cataract surgery. Moreover, they plan to explore the potential expansion of MELT-300's use to other medical specialties, including dermatology, plastic surgery, dentistry, gastroenterology, and emergency care, potentially addressing over 100 million annual procedures.
