As the crushing burden of opioid addiction grows, companies such as Latigo Biotherapeutics and Vertex Pharmaceuticals are working to develop new, safer, and more effective non-opioid painkillers. It’s a huge unmet need and an opportunity. Non-addictive pain drugs represent a growing market that is expected to be worth over $30B this year. Both companies are currently focused on selective NaV1.8 inhibitors.
This week, Latigo announced its emergence from stealth with a $135 million Series A financing. Westlake Village BioPartners, which incubated the company, led the financing. Latigo’s lead candidate is NaV1.8 inhibitor LTG-001. But Latigo is chasing Vertex, which is ahead of the game with its NaV1.8 inhibitor, VX-548. In January of this year, Vertex announced positive Phase III results that were soon after published in The New England Journal of Medicine.
Opioid addiction is a major crisis. According to the CDC, in the U.S. more than one million people have died since 1999 from a drug overdose, more than 75% of these deaths involved an opioid in 2021 alone. The number of overdose deaths involving opioids, including prescription opioids, heroin, and synthetic opioids (like fentanyl), in 2021 was 10 times the number in 1999.
Opioids attach to opioid receptors on nerve cells in the brain, spinal cord, gut, and other places. When this happens, the opioids block pain messages sent from the body through the spinal cord to the brain. While they are very effective, these drugs are highly addictive, especially with chronic use.
Alternatives do exist. NSAIDs non selectively inhibit the cyclooxygenase enzymes (isoenzymes 1 and 2). While they are widely used, these drugs pose a potentially serious risk of gastrointestinal toxicity, hematologic toxicity, and nephrotoxicity, especially with chronic use.
Latigo’s LTG-001, is an oral, selective Nav1.8 inhibitor currently in a Phase I clinical trial in healthy volunteers and intended to treat acute and chronic pain. In its press release, the company reports “LTG-001 has the potential to be best-in-class with a rapid onset, meaningful efficacy, and superior safety to standard of care with no central nervous system effects.” Beyond Nav1.8, the company has a pipeline of novel, genetically identified targets with small molecule programs at the discovery stage.
In January, Vertex announced positive results from its Phase III program for VX-548 in the treatment of moderate-to-severe acute pain. The Phase III program included two randomized, double-blind, placebo-controlled, pivotal trials, one following abdominoplasty surgery and one following bunionectomy surgery, as well as a single arm safety and effectiveness study which enrolled patients with a broad range of surgical and non-surgical pain conditions.
Treatment with VX-548 following abdominoplasty or bunionectomy led to a statistically significant improvement on the primary endpoint of the time-weighted sum of the pain intensity. For the first key secondary endpoint, Vertex tested the hypothesis that VX-548 was superior to hydrocodone bitartrate/acetaminophen following abdominoplasty surgery or bunionectomy surgery. Neither trial met this key secondary endpoint.
The second key secondary endpoint in both trials was time to meaningful pain relief. VX-548 had a more rapid onset to meaningful pain relief than placebo in both the abdominoplasty and bunionectomy trials. VX-548 was safe and well tolerated.
“We are very pleased with the results from the VX-548 pivotal program, which demonstrate a compelling and consistent combination of efficacy and safety across multiple acute pain conditions and settings. The VX-548 benefit-risk profile ideally positions it to potentially fill the gap between medicines with good tolerability but limited efficacy and opioid medicines with therapeutic efficacy but known risks, including addictive potential,” said Reshma Kewalramani, MD, CEO and president of Vertex.
