SAN DIEGO and OSAKA, Japan—Perhaps taking inspiration from the adage "Those who don't learn from history are doomed to repeat it," Amylin Pharmaceuticals Inc. and Takeda Pharmaceutical Co. Ltd. announced March 16 that they have suspended clinical activities in an ongoing Phase II study examining the safety and effectiveness of the investigational combination therapy of pramlintide and metreleptin for the treatment of obesity.
The historical aspect comes in from two directions, it would seem. In a more "macro" sense, this seeming setback occurs at a time when several new obesity drugs have failed to pass muster with regulators, mostly because of safety issues rather than efficacy, and thus failed to reach the market. So, both companies may want to tread carefully because of that, particularly with many Japanese pharmas and other companies hoping to replace older pipeline products that are going up against increasing generic completion and failing to do so. In addition, Takeda is already partnered with Orexigen Therapeutics Inc. on the diet pill Contrave, which got a thumbs-down from the U.S. Food and Drug Administration (FDA) along with a request for a rigorous new clinical trial.
In a more "micro" sense, the two partners are making this call because of data from a previous trial. That is, the current trial was halted not because of anything going on right now with participants, but rather because of some data from a trial that produced results in 2009—and even those results weren't related to dramatic adverse health events. Rather, the current clinical study was voluntarily halted to investigate a new antibody-related laboratory finding with metreleptin treatment in two patients who participated in that previous clinical study of obesity, because of suggestions that "neutralizing activity to metreleptin (and leptin) may have occurred," according to an Amylin spokesperson.
Amylin notes that there is limited information to work from right now, so the long-term implications for this trial and the collaboration between it and Takeda are unknown, but notes that metreleptin has been studied for more than 14 years in several types of patients and has been generally well-tolerated historically.
"The safety of patients in our clinical programs is of paramount concern to the companies," says Dr. Orville Kolterman, senior vice president and chief medical officer of Amylin. "We have taken this precaution so that we can thoroughly investigate this finding. Together with our partner, Takeda, we are committed to working closely with clinical investigators, regulators and outside experts to determine the best path forward."
Amylin stresses that the announcement does not affect its lipodystrophy development program that is investigating the use of metreleptin to treat diabetes and/or hypertriglyceridemia in patients with rare forms of lipodystrophy—a program independent of the collaborative work with Takeda.
Pramlintide acetate is a synthetic analog of the natural hormone amylin, a neurohormone secreted by the pancreas that is known to play a role in the regulation of appetite, food intake and postprandial glucose concentrations. To date, approximately 8,000 individuals have received pramlintide in clinical trials, including more than 950 in obesity studies. Metreleptin (methionyl recombinant leptin; r-metHuLeptin) is an analog of human leptin, a neurohormone secreted by fat cells that plays a fundamental role in the regulation of energy metabolism and body weight. To date, more than 1,200 overweight or obese individuals have received metreleptin in clinical trials, several of which were 16 weeks or longer in duration.
Looking at Takeda's other setback, in its collaboration with Orexigen, the latter company actually announced a corporate realignment just a week after the bad news from the FDA, saying on Feb. 9 that it would lay off 23 staff—about 40 percent of its workforce—and citing the complete response letter from the FDA as the reason.
"We continue to believe in the potential of Contrave and look forward to discussions with the FDA," said Mike Narachi, Orexigen CEO, at the time. "Unfortunately, given the near term uncertainty of Contrave approval, we felt it prudent to consolidate and focus our resources."
The historical aspect comes in from two directions, it would seem. In a more "macro" sense, this seeming setback occurs at a time when several new obesity drugs have failed to pass muster with regulators, mostly because of safety issues rather than efficacy, and thus failed to reach the market. So, both companies may want to tread carefully because of that, particularly with many Japanese pharmas and other companies hoping to replace older pipeline products that are going up against increasing generic completion and failing to do so. In addition, Takeda is already partnered with Orexigen Therapeutics Inc. on the diet pill Contrave, which got a thumbs-down from the U.S. Food and Drug Administration (FDA) along with a request for a rigorous new clinical trial.
In a more "micro" sense, the two partners are making this call because of data from a previous trial. That is, the current trial was halted not because of anything going on right now with participants, but rather because of some data from a trial that produced results in 2009—and even those results weren't related to dramatic adverse health events. Rather, the current clinical study was voluntarily halted to investigate a new antibody-related laboratory finding with metreleptin treatment in two patients who participated in that previous clinical study of obesity, because of suggestions that "neutralizing activity to metreleptin (and leptin) may have occurred," according to an Amylin spokesperson.
Amylin notes that there is limited information to work from right now, so the long-term implications for this trial and the collaboration between it and Takeda are unknown, but notes that metreleptin has been studied for more than 14 years in several types of patients and has been generally well-tolerated historically.
"The safety of patients in our clinical programs is of paramount concern to the companies," says Dr. Orville Kolterman, senior vice president and chief medical officer of Amylin. "We have taken this precaution so that we can thoroughly investigate this finding. Together with our partner, Takeda, we are committed to working closely with clinical investigators, regulators and outside experts to determine the best path forward."
Amylin stresses that the announcement does not affect its lipodystrophy development program that is investigating the use of metreleptin to treat diabetes and/or hypertriglyceridemia in patients with rare forms of lipodystrophy—a program independent of the collaborative work with Takeda.
Pramlintide acetate is a synthetic analog of the natural hormone amylin, a neurohormone secreted by the pancreas that is known to play a role in the regulation of appetite, food intake and postprandial glucose concentrations. To date, approximately 8,000 individuals have received pramlintide in clinical trials, including more than 950 in obesity studies. Metreleptin (methionyl recombinant leptin; r-metHuLeptin) is an analog of human leptin, a neurohormone secreted by fat cells that plays a fundamental role in the regulation of energy metabolism and body weight. To date, more than 1,200 overweight or obese individuals have received metreleptin in clinical trials, several of which were 16 weeks or longer in duration.
Looking at Takeda's other setback, in its collaboration with Orexigen, the latter company actually announced a corporate realignment just a week after the bad news from the FDA, saying on Feb. 9 that it would lay off 23 staff—about 40 percent of its workforce—and citing the complete response letter from the FDA as the reason.
"We continue to believe in the potential of Contrave and look forward to discussions with the FDA," said Mike Narachi, Orexigen CEO, at the time. "Unfortunately, given the near term uncertainty of Contrave approval, we felt it prudent to consolidate and focus our resources."
