Zafgen‘s investigative therapy ZGN-1258, under development as a treatment for Prader-Willi syndrome, is being evaluated in preclinical studies as it moves toward clinical trials in humans, according to the biopharmaceutical company.
The results of this initial phase are expected to support the submission of an investigational new drug (IND) application to the U.S. Food and Drug Administration, and promote the initiation of first in-human clinical trials.
The company anticipates launching a Phase 1 trial of ZGN-1258 by the end of 2018, Zafgen stated in a press release.
The company is also planning to start a global natural history study in Prader-Willi syndrome to expand knowledge about the disorder and its long-term outcomes, providing valuable context for the ZGN-1258 clinical program.
Zafgen expects to forge collaborations with patient advocacy groups and the FDA for the design of this study, which is expected to start in the middle of 2018.
Zafgen has been focused on the development of drug candidates that can specifically target the MetAP2 pathway as a way to treat obesity and other complex metabolic diseases. MetAP2 is known to play a central role in metabolic disorders.
Several years ago, Zafgen was working toward the development of MetAP2 inhibitor beloranib (ZGN-440) as a possible treatment for Prader-Willi syndrome.
Results from a Phase 3 trial (NCT02179151) published in 2017 showed that the experimental therapy could help patients significantly reduce body weight by up to 9.5% compared to placebo in about 26 weeks.
However, beloranib was found to have a negative impact on cells lining blood vessels, leading to blood clot formation and the occurrence of serious adverse events. During the trial, two fatalities and two cases of life-threatening events were reported, leading to the termination of the trial and the end of Zafgen’s development of beloranib.
In January 2018, Zafgen announced its comeback to the field of rare metabolic disorders with a second, highly selective MetAP2 inhibitor.
ZGN-1258 was designed to change the way the body uses fat molecules, reducing fat mass and controlling the urge to eat excessively associated with Prader-Willi syndrome.
Compared to the previous version of the inhibitor, ZGN-1258 has been shown to have the potential to act on adipose tissue and also on hunger control centers.
Initial preclinical data showed that ZGN-1258 can induce similar weight loss in mice as beloranib, but without triggering the serious, life-threatening effects on blood vessel cells.
“Zafgen is building significant momentum across our pipeline in 2018, following intense foundational scientific work in 2017,” Jeffrey Hatfield, CEO of Zafgen, said in the January press release.
“The positive interim clinical data from our ongoing Phase 2 proof-of-concept trial with ZGN-1061, as well as the initiation of IND enabling studies with ZGN-1258, demonstrate important progress across our two most advanced programs,” Hatfield added.
ZGN-1061 is Zafgen’s lead product candidate, a MetAP2 inhibitor under development for the treatment of type 2 diabetes and other related metabolic disorders.