Zafgen, a biopharmaceutical company dedicated to significantly improving the health and well-being of patients affected by obesity and complex metabolic disorders, has announced that the company has recently initiated dosing in the multiple ascending dose (MAD) cohorts of its ongoing phase I clinical trial of ZGN-1061. The initiation of the MAD portion was triggered following a review of the initial safety and tolerability data from the first two cohorts of the single ascending dose (SAD) portion of the clinical trial. ZGN-1061 is a second-generation, differentiated MetAP2 inhibitor in development for severe and complicated obesity indications.
“For the last decade Zafgen has been studying the MetAP2 pathway to inform the development of molecules that will leverage the powerful benefits of MetAP2 inhibition, while minimizing off-target effects. Based on this work we have optimized ZGN-1061 to deliver an efficacy and safety profile appropriate for development in prevalent obesity-related disorders,” said Thomas Hughes, Ph.D., president and chief executive officer of Zafgen. “This clinical trial is an important first step as we look to validate the clinical profile of ZGN-1061. Initial results show ZGN-1061 exhibits pharmacokinetic properties in humans within our specified target range, translating to encouraging early safety and tolerability that support our plans for continued development of this promising candidate.”
The phase I clinical trial is evaluating safety, tolerability, and weight loss efficacy over four weeks of treatment. The clinical trial includes a SAD portion, which will enroll up to 48 healthy subjects across up to six cohorts of single escalating doses of ZGN-1061. The clinical trial also includes a MAD portion, which is evaluating twice-weekly ZGN-1061 over four weeks in up to 24 obese subjects. Key elements of the clinical trial involve evaluation of the uptake and elimination of ZGN-1061, or pharmacokinetics, and evaluation of endpoints related to blood coagulation. The Company continues to expect top-line data from the clinical trial by the end of the first quarter of 2017.
ZGN-1061, is a fumagillin-class MetAP2 inhibitor that originated from Zafgen's discovery program as part of a multi-year campaign to identify novel compounds that avoided limiting preclinical safety concerns observed with its first-generation MetAP2 inhibitor, beloranib, including teratogenicity and adverse effects on testicular function. The compound has metabolic efficacy, potency, and range of activity in animal models of obesity similar to beloranib, but displays highly differentiated safety properties and a reduced potential to impact thrombosis, supporting the value of the compound as a more highly optimized MetAP2 inhibitor.
“The clinical trial is progressing well, and we are particularly encouraged that there have been no significant safety signals or tolerability concerns observed in patients treated to date,” stated Dennis Kim, M.D., chief medical officer of Zafgen. “We look forward to further advancing this clinical trial, the results of which will provide us with important insights on the potential of ZGN-1061 in severe and complicated obesity, and help inform the doses, design, and patient population for our phase II program.”