Only six weeks ago, Durect’s phase IIa trial of DUR-928 for treating alcoholic hepatitis came out a winner when the principal investigator presented positive phase IIa data to the AASLD’s Liver Meeting in Boston. But it was a different story Thursday when the company announced it decided to discontinue development of DUR-928 in psoriasis based on results from its phase IIa trial in patients with mild to moderate plaque psoriasis.
The failure and subsequent decision to bow out of psoriasis knocked Durect’s stock (NASDAQ:DRRX) a few steps backward, closing 31% lower at $2.61 per share on Thursday. The day tipped the shares a little closer to the price they commanded before their dramatic rise began in mid-December. On Dec. 16, shares went for $1.88 each and rose a dramatic 102% to $3.80 by the time the market closed on New Year’s Eve.
DUR‑928, designed to modulate nuclear receptors, is the lead candidate in the company’s Epigenetic Regulator program.
The different indications depended on the mode of administration. The failed psoriasis study was of a topical version of DUR-928, which is a sulfated oxysterol. An oral version is in phase I for nonalcoholic steatohepatitis (NASH). For the alcoholic hepatitis trial reported at AASLD in Boston, the drug was given via intravenous infusion.
James E. Brown, Durect’s president and CEO, said the company is moving forward with DUR-928 by “completing the NASH trial in the first half of this year and initiating the phase IIb [alcoholic hepatitis] trial in the middle of the year."
In the psoriasis trial, DUR-928 failed to demonstrate a benefit over placebo in the primary and secondary analyses. In the randomized, double-blind, vehicle-controlled, multicenter, proof-of-concept study, DUR-928 was applied topically once daily for 28 days with a 28-day follow-up period in patients with mild to moderate plaque psoriasis. The trial was conducted in the U.S. Each patient was their own control, applying DUR-928 to the plaque on one arm and the placebo to a similar plaque on the other arm. After the treatment period, patients were followed for an additional four weeks.
DUR-928’s daily topical application was well-tolerated with no meaningful differences in adverse events between the treatment and placebo groups. There were no adverse events attributed to the drug.
The different modes of administration, Durect's senior vice president of research and development, WeiQi Lin, told BioWorld, affect where the drug ends up. With oral administration, most of the drug stays in the liver, while "the blood carries it all over the body" after an intravenous infusion. That is an advantage in alcoholic hepatitis, which results from binge drinking that "gives the liver acute hepatitis from the toxins in the alcohol to the extent that other organs start to shut down," Brown said. Intravenous administration, he added, "protects the liver and the lungs and the kidney... You want to rescue their lives, not only their liver."
Abbvie Inc.’s Skyrizi (risankizumab) won FDA approval for adults with moderate to severe plaque psoriasis in April. It is expected to launch in the U.S. in early May.
In December 2018, Innovation Pharmaceuticals Inc., of Beverly, Mass., reported preliminary top-line results for its phase IIb trial showing oral Prurisol, a small-molecule immune modulator for treating moderate to severe chronic plaque psoriasis, failed to meet the primary endpoint in either treatment arm (300 mg and 400 mg). The company said it would discontinue its Prurisol psoriasis program.
In August 2016, Mayne Pharma Inc., of Greenville, N.C., acquired a portfolio of already-marketed dermatology foam assets from London-based Glaxosmithkline plc for $50.1 million, including the U.S. rights to the mild to moderate plaque psoriasis treatment Sorilux (calcipotriene).