A Levo Therapeutics drug designed to curb the insatiable hunger experienced by people with Prader-Willi syndrome fails at FDA as regulator Refuse The biotech’s drug application also calls for another clinical trial.
refuse to follow vote In November, an FDA advisory committee recommended against approving the drug, LV-101, citing a lack of evidence to support the drug’s efficacy. Chicago-based Levo said on Tuesday it was in discussions with the FDA about the design of a new clinical study to confirm the drug’s efficacy. Meanwhile, the privately held company continues to offer the drug to existing clinical trial participants.
Prader-Willi is a rare metabolic disorder caused by a genetic mutation. People with this disorder lose their sense of satiety with food, leading to the urge to keep eating. Obesity from Prader-Willi increases the risk of potentially life-threatening heart and breathing problems.
There is currently no FDA-approved Prader-Willi therapy. The way Levo treats this disease is hormones. Human behavior, including social bonding and appetite, is regulated by a hormone called oxytocin. People with Prader-Willi had fewer oxytocin-producing neurons in the hypothalamic glands, according to Levo. Levo is designed to increase oxytocin levels to reduce hunger.Clinical studies that have been carried out show that Assess oxytocin to treat disease. Levo’s LV-101 is carbetocin, an analog of natural oxytocin. Levo drugs are designed to be highly selective for binding to the oxytocin receptor.
Oxytocin also has a role in addressing postpartum hemorrhage. This hormone is given to mothers to help the uterus contract and prevent excessive bleeding. Carbetocin has been used as a treatment to prevent postpartum hemorrhage. The drug is approved for this application worldwide, but is not currently FDA-approved for any indication. Ferring Pharmaceuticals, which sells carbetocin to prevent postpartum hemorrhage, is advancing an intranasal version of the drug into Phase 2 testing of Prader-Willi. In 2016, Levo licensed Global rights to a Phase 3-ready drug for the treatment of Prader-Willi.
Levo tested LV-101 in a placebo-controlled, double-blind study of 175 Prader-Willi patients. Patients were randomly assigned to receive a 3.2 mg dose of study drug, a 9.6 mg dose of study drug, or placebo for eight weeks. The two main goals were to show changes in scores according to a scale used to assess extreme hunger and a scale used to measure obsessive-compulsive symptoms.
2020, Lever report The data showed that high doses did not reach statistical significance on measures of starvation or compulsive measures. In the low-dose group, Levo reported statistical significance based solely on the hunger measure. The New Drug Application for LV-101 is based on this result. In clinical trials, patients found the Levo drug to be safe and well tolerated.
The FDA did not make the full response letter public, but according to Levo, the agency said data from the proposed 3.2 mg dose of the drug were insufficient to support approval.according to FDA briefing document The results of the pivotal study were unclear, the agency told the company as it prepared for the advisory committee meeting. The FDA also said that because Prader-Willi may require long-term treatment, a longer study of Levo is needed.
Prader-Willi has proven to be a challenge for drug developers. Zafgen’s efforts to develop Prader-Willi drug are marked by problems in clinical trials, including patient deaths and clinical hold. Millendo Therapeutics reported in 2020 that its Prader-Willi drug lose in mid-term testing. Both Zafgen and Millendo ended those plans, and the companies could only survive by serving as vehicles for taking other biotechs to market.
In a prepared statement, Levo CEO Sara Cotter said her company was disappointed by the FDA’s review of the LV-101 drug application and the continued lack of treatment for Prader-Willi’s most prominent symptoms.
Cotter added: “We hope our discussions with the FDA on the next study will be fruitful and that we can initiate registration of a confirmatory study later this year.”
Food and Drug Administration photo
