Trevi Therapeutics is trying to turn an old opioid drug into a new therapy for tough-to-treat itching conditions, and it has filed for an initial public offering to finance clinical trials.
In paperwork submitted to the SEC late Friday, Trevi set a preliminary $86 million target for its IPO. The New Haven, CT-based company has applied for a Nasdaq listing under the stock symbol “TRVI.”
Trevi’s drug candidate, nalbuphine ER, is an extended-release formulation of nalbuphine hydrochloride, an opioid. Injectable nalbuphine has been used to treat pain for decades. Trevi says it has developed an oral formulation of the drug that targets the kappa and mu opioid receptors, both of which mediate itching and coughing. These receptors also play a role in certain movement disorders.
Trevi says that its drug’s dual mechanism of action reduces the risk of abuse. On mu receptors, which trigger the reward systems in the brain that kick off addiction, nalbuphine blocks activity. Although nalbuphine is an opioid, it is not a controlled substance. In 1976, the predecessor to the U.S. Department of Health and Human Services removed the drug’s Schedule II classification, the designation for drugs that have a high potential for abuse.
The lead disease target for Trevi’s drug is prurigo nodularis, a rare disorder that leads to the formation of itchy lumps on the skin. In some cases, the intense itching leads patients to scratch until their skin bleeds. The cause of the disease is not known.
Nalbuphine ER has produced mixed results in clinical trials so far. Trevi tested its drug in a Phase 2 study enrolling 63 prurigo nodularis patients who had moderate-to-severe itching. Neither the 162-milligram dose nor the 81-milligram dose met the main goal of at least a 30 percent reduction in itching scores after 10 weeks, according to the IPO filing.
Trevi says the data look more encouraging after looking at a subset of patients. Of the 50 patients who completed the 10-week course of treatment, Trevi says half of them reported a 50 percent reduction in itching scores compared with 20 percent of those in the placebo group. After discussing the findings with the FDA, Trevi started a Phase 2b/3 study last September. The company says it can get better results by reducing the discontinuation rates of study volunteers. Preliminary data are expected in the first half of next year.
If nalbuphine ER is approved to treat prurigo nodularis, Trevi says the drug would compete against a number of drugs used off-label to treat the disorder, including topical anti-itch medications; oral and injectable antihistamines; and gabapentin and pregabalin (Lyrica), two drugs that are approved to treat seizures and neuropathic pain.
Experimental therapies that could compete against Trevi’s drug include serlopitant, a Menlo Therapeutics (NASDAQ: MNLO) drug that blocks the neurokinin-1 receptor. Menlo is testing serlopitant is in Phase 3 testing in purigo nodularis, but the drug’s clinical trial track record in other diseases to date has been disappointing. Other potential competitors to Trevi’s drug include experimental antibody therapies in development by Nestle subsidiary Galderma, as well as Kiniksa Pharmaceuticals (NASDAQ: KNSA).
Trevi is also testing nalbuphine ER as a potential treatment for uremic pruritus, the itching experienced by chronic kidney disease patients receiving dialysis. The company has tested two doses of the drug in a Phase 2b/3 study enrolling 373 patients. The group treated with the 108-milligram dose met the main goal of improving itching scores. The 54-milligram dose led to an improvement in itching scores, but not enough to be statistically significant, the company says.
Trevi’s other disease targets for nalbuphine ER include the coughing associated with idiopathic pulmonary fibrosis (IPF) and the involuntary movements experienced by Parkinson’s disease patients treated with levodopa. Trevi plans to start a Phase 2 study in IPF patients in the first half of this year. Another Phase 2 study in Parkinson’s patients is planned for the second half of this year.
Nalbuphine ER traces its origins to Penwest Pharmaceuticals, a company that had a proprietary drug delivery technology for extended-release drug formulations. In 2010, Endo Pharmaceuticals (NASDAQ: ENDP) acquired Penwest for approximately $168 million. Trevi was formed in 2011 around assets licensed from Endo.
Since launching, Trevi has raised $92.2 million in financing, according to the filing. TPG Biotech is the largest shareholder with a 55.2 percent stake. Other investors include New Enterprise Associates, Lundbeckfond Invest, and Omega Funds.