AbbVie and Ironwood Halt Development of IBS-D Candidate MD-7246 Following Phase II Failure

Compiled by Keke

Latest topline data show that the Phase 2 clinical trial of MD-7246 for improving abdominal pain symptoms in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) failed to meet its primary and key secondary endpoints. AbbVie and Ironwood Pharmaceuticals have decided to halt the development of this experimental non-opioid analgesic. Following the announcement, Ironwood’s stock price fell by 12.4%.

On May 27, Ironwood Pharmaceuticals released the primary data from the randomized, double-blind, placebo-controlled Phase 2 clinical trial NCT03931785. This trial aimed to evaluate the safety, tolerability, and efficacy of MD-7246 in alleviating abdominal pain symptoms in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). The study enrolled a total of 388 adults with IBS-D-associated abdominal pain. MD-7246 was administered in three dose groups (300 μg, 600 μg, and 1200 μg), with patients randomly assigned to receive once-daily MD-7246 or placebo. The primary efficacy endpoints were the change from baseline in weekly worst abdominal pain scores and the overall abdominal pain response rate, defined as achieving at least a 30% reduction in abdominal pain compared to baseline in at least 6 out of 12 weeks.

The results showed that, compared with placebo, MD-7246 did not significantly improve abdominal pain in patients with IBS-D. Furthermore, MD-7246 was generally well tolerated, with most adverse events being mild to moderate in severity. The most common adverse events were upper respiratory tract infection/nasopharyngitis, with an incidence similar to that of placebo.

In the United States, approximately 16 million people suffer from IBS-D. These patients report frequent abdominal pain (averaging about 86 days per year), abdominal discomfort, and bloating, accompanied by looser or more frequent stools than usual. More than 80% of surveyed IBS-D patients report moderate to severe symptoms.

MD-7246, an investigational drug, is a sustained-release formulation of linaclotide designed to release the active ingredient in the distal ileum near the ileocecal junction. Consequently, it has the potential to alleviate abdominal pain with limited effects on the intestines. Linaclotide is a major branded prescription medication in the field of constipation treatment and has been approved in the United States for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in adults. The marketing rights to this drug were initially held jointly by Ironwood Pharmaceuticals and Allergan; following the acquisition of Allergan by AbbVie, the drug was renamed Linzess.

Previously, MD-7246 advanced to Phase 3 clinical trials for the treatment of IBS-C and demonstrated promising results. Ironwood pointed out that the results of a double-blind, placebo-controlled, dose-ranging Phase 2b clinical trial of MD-7246 in adult patients with IBS-C, announced in December 2016, showed that compared to placebo, the drug numerically improved abdominal pain and other abdominal symptoms (such as bloating and discomfort). For abdominal pain, the percentage change from baseline at Week 12 was -33.8% to -36.6% in the MD-7246 group, compared to -26.2% in the placebo group. However, it did not show a significant effect on bowel movement function.

These data support the evaluation of MD-7246’s therapeutic efficacy in patients with IBS-D. In June 2019, Ironwood and Allergan again reported the primary data from the Phase 3b clinical trial, demonstrating that MD-7246 improved overall abdominal bloating, distension, and discomfort in adults with IBS-C, meeting all primary and secondary endpoints. Nevertheless, both companies decided to suspend the development of MD-7246, possibly due to its lack of distinct therapeutic advantages, which could lead to poor market competitiveness.

Ironwood stated that AbbVie is reviewing the latest results to understand the reasons for the inconsistent efficacy of MD-7246 in IBS patients with two different symptom profiles.

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AbbVie, Ironwood abandon IBS drug MD-7246 after failed Phase II trial