Urovant’s Irritable Bowel Drug Fails in Phase II; Genmab Abandons Cancer Drug
Even companies with otherwise promising pipelines or successful products on the market sometimes face clinical trial failures. Two such companies, Urovant Sciences and Genmab, had disappointing clinical trial announcements today.
Urovant Sciences announced topline data from the Phase IIa trial of once-daily vibegron in women with abdominal pain due to irritable bowel syndrome (IBS) with IBS-D (diarrhea) and IBS-M (mixed IBS). The trial failed to meet the primary endpoint with 40.9% of vibegron IBS-D patients achieving at least a 30% improvement in average worst abdominal pain over a 12-week period. The placebo group was 42.9%.
The trial defined a responder as a subject with at least a 30% decrease in “worst abdominal pain in the past 24 hours” compared to the weekly baseline average over the 12-week period. The company indicated the most important secondary endpoint showed a 42.4% of Global Improvement Scale (GIS) responders at Week 12 for IBS-D patients in the vibegron group compared to 33.3% in the placebo group. However, this was not statistically significant for IBS-D, IBS-M or the overall IBS population.
“While we are disappointed by the topline results from this Phase IIa trial, we want to sincerely thank the patients, investigators and their site staff who participated,” said Cornelia Haag-Molkenteller, chief medical officer of Urovant. “We look forward to advancing our Phase III program for vibegron in men with overactive bladder and benign prostatic hyperplasia (BPH), as well as our Phase IIa program for URO-902 in OAB and look forward to the U.S. Food and Drug Administration’s (FDA) upcoming assigned Prescription Drug User Fee Act (PDUFA) goal date of December 26, 2020, for the New Drug Application (NDA) for vibegron to treat overactive bladder (OAB).”
Vibegron is an oral, once-daily small molecule beta-3 agonist.
IBS is marked by recurrent abdominal pain associated with two or more of the following symptoms: defecation, change in stool frequency, and/or change in stool or appearance. In the U.S., about 30 million to 40 million people have symptoms of IBS, with 30% in consult with a physician. About 80% of these patients say pain is a symptom that contributes to the severity of the disease.
Copenhagen, Denmark-based Genmab A/S reported that it plans to halt development of enapotamab vedotin. They note that while the drug provided some evidence of clinical activity, it was not optimized by different dose schedules or predictive biomarkers. The data from the expansion cohorts failed to meet the company’s criteria for proof-of-concept.
The drug is an AXL targeted Antibody-Drug Conjugate (ADC). An ADC is a monoclonal antibody attached to a cancer drug with a molecular linker. In this case, a monoclonal antibody for AXL is conjugated to the antimitotic drug monomethyl auristatin E. AXL is overexpressed in hematologic and solid malignancies.
“We are committed to developing innovative antibody products for patients with cancer, however, the data from the enapotamb vedotin expansion cohorts unfortunately does not support moving this product candidate forward,” said Jan van de Winkel, Genmab’s chief executive officer. “This decision will allow us to focus more of our resources and energy on other programs in our robust next-generation antibody therapeutics pipeline.”
The drug is fully owned by Genmab. The drug linker technology used for the ADC is licensed from Seagen. It had demonstrated preclinical antitumor activity in solid tumors, including non-small cell lung cancer (NSCLC) with and without EGFR mutations.
Company shares were down 2.1% at the news.