Lademirsen

Shutterstock Sanofi has terminated a development agreement with Regulus in Alport syndrome, while Merck reaches the point of futility in a Phase III colorectal cancer trial. Shares of Regulus Therapeutics plunged nearly 10% Monday after the company disclosed that its partner Sanofi has terminated a development agreement for a small RNA molecule inhibitor being developed for Alport syndrome. In a filing with the U.S. Securities and Exchange Commission, Regulus said Sanofi has opted to terminate the Phase II clinical development of lademirsen (previously known as RG-012) for the treatment of Alport syndrome, a genetic disease that causes kidneys to progressively lose the ability to filter waste products from the blood. Sanofi indicated that it intends to evaluate different opportunities for lademirsen. In February, Regulus announced that the Phase II HERA study for Alport syndrome had completed enrollment. The trial was designed to assess the safety and efficacy of the experimental drug. Results were expected in the second half of 2023. In the filing, Regulus said the termination was due to the trial’s “failure to meet Sanofi’s pre-defined futility criteria,” but did not elaborate further. Sanofi gained control of lademirsen’s development in 2018 following a restructuring of a collaboration agreement between the two companies. If the HERA study were completed, Regulus would have gained $25 million from a milestone payment. The California-based company remains eligible for other milestones from completion of a Phase II fibrosis proof of concept study, Regulus said in its filing. There are currently no specific therapies approved in the U.S. for Alport syndrome. Earlier this year, the U.S. Food and Drug Administration issued a Complete Response Letter to Reata Pharmaceuticals regarding its experimental treatment citing a “lack of proof of effectiveness.” The regulatory agency said Reata’s bardoxolone methyl (bardoxolone) failed to demonstrate the ability to reduce the risk of progression to kidney failure. Merck Reaches Futility in Phase III Colorectal Cancer Trial Sanofi wasn’t the only company to halt a clinical trial this week. On Monday, pharma giant Merck announced it has halted the Phase III LYNK-003 trial evaluating PARP inhibitor Lynparza for patients with unresectable or metastatic colorectal cancer who have not progressed following first-line induction. The decision was based on the recommendation of an independent Data Monitoring Committee following tis review of data at an interim analysis. The committee reviewed the data for progression-free survival. Following the review, the committee said Lynparza, as a monotherapy and in combination with Genentech’s Avastin (bevacizumab), “met the criteria for futility.” Lynparza, an immuno-oncology drug, is being co-developed and co-commercialized with AstraZeneca. Merck said it will inform patients and study investigators about the decision. The Phase III LYNK-003 study included 309 patients with unresectable or metastatic colorectal cancer. In addition to colorectal cancer, Merck and AstraZeneca are assessing Lynparza as both a monotherapy and in new combinations across a range of DNA damage response deficient tumor types, including metastatic prostate cancer, ovarian cancer, breast cancer and pancreatic cancer.