OSAKA, Japan—Takeda Pharmaceutical Company Limited announced today that it has decided voluntarily to terminate the development activities for fasiglifam (TAK-875), an investigational treatment for type 2 diabetes, due to concerns about liver safety. TAK-875 is a selective GPR40 agonist with EC50 of 14 nM, which was said to be 400-times more potent than oleic acid. Prior to this announcement the product had been offered for sale for experimental use in the Takeda online catalog. The Takeda website notes that “In a rat model of diabetes, single oral dosing of TAK-875 at 0.3-3 mg/kg reduces the blood glucose excursion and augments insulin secretion during an oral glucose tolerance test, when TAK-875 is administered 1 hour before an oral glucose challenge. In type 2 diabetic N-STZ-1.5 rats, administration of TAK-875 (1-10 mg/kg p.o.) shows a clear improvement in glucose tolerance and augments insulin secretion. Additionally, TAK-875 (10 mg/kg, p.o.) significantly augments plasma insulin levels and reduces fasting hyperglycemia in male Zucker diabetic fatty rats, whereas in fasted normal Sprague-Dawley rats, TAK-875 neither enhances insulin secretion nor causes hypoglycemia even at 30 mg/kg.”
Takeda executives had frequently pointed to TAK-875 as a prime candidate to replace at least in part the sales lost when their type 2 diabetes treatment Actos went off patent. That drug was responsible for about one-quarter of Takenda’s sales. TAK-875 was designed to spur insulin secretion in the pancreas and Takeda had confidently projected an approval in Japan in 2015 with a follow-up approval in the U.S. market a year or two later.
The termination of the high-profile program caused Takeda's shares to drop 8 percent as analysts wondered how the pharma could counter the loss of Actos, a $3.7 billion drug that accounted for about a quarter of company revenue in 2011.
Takeda stated that “Patient safety is Takeda’s highest priority. The company has worked with three independent panels of experts to provide for the safety of trial participants and ensure independent safety oversight for the clinical trials throughout the duration of the fasiglifam (TAK-875) Phase 3 development program.”
The expert panels include the independent Data Monitoring Committee (DMC), a committee that oversees the fasiglifam global clinical development program, reviews the unblinded clinical data from program trials and provides continual safety oversight of trial subjects and recommendations. The DMC is comprised of clinical experts in endocrinology, cardiology and hepatology as well as a statistician. The independent Liver Safety Evaluation Committee (LSEC) is comprised of five hepatologists with expertise in drug-induced liver injury. While remaining blinded to treatment information, the LSEC regularly evaluates data on liver enzymes elevations and adjudicates cases that impacted the liver. In addition, an independent Executive Committee (EC) provides additional oversight for the fasiglifam (TAK-875) cardiovascular outcomes trial.
After careful consideration of the data emerging from all the clinical trials and in consultation with these panels, the company reached the conclusion that, on balance, the benefits of treating patients with fasiglifam (TAK-875) do not outweigh the potential risks. For this reason, Takeda has decided voluntarily to terminate the development activities for fasiglifam.
Takeda is in communication with trial investigators and the relevant regulatory authorities regarding the company’s decision, to provide them with updated and current information in compliance with local regulations. Takeda is working with trial investigators and local regulatory authorities to ensure that patients who participated in the fasiglifam (TAK-875) trials are transitioned to appropriate therapies and ensure that trial participants receive appropriate care. Patients enrolled in the fasiglifam (TAK-875) clinical trials are urged to consult their study investigators to address any questions, and before making any changes to their medication.
In its press release, Takeda stated that it remains committed to the development of novel treatments for diabetes, a disease which represents a growing health burden for people worldwide.
Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, the company emphasizes that it remains committed to strive towards better health for people worldwide through leading innovation in medicine.
Source: Takeda Pharmaceuticals