Welcome to your weekly digest of approaching regulatory and clinical readouts. Vanda Pharmaceuticals is awaiting two important clinical readouts by the end of 2018: data from a study evaluating Hetlioz in reducing sleep disturbances in the rare Smith-Magenis syndrome, and results from a trial of tradipitant in gastroparesis.
Hetlioz is already approved for non-24-hour sleep-wake disorder, which affects blind people who do not have environmental visual cues about nightfall. It is on track to achieve more than $100m in sales in 2018 in this indication alone, but a label expansion should add to that figure.
Smith-Magenis syndrome is a genetic disorder that leads to intellectual disability and behavioural problems. Among the symptoms are sleep disturbances, along with shortened sleep cycles and wakefulness during the night, something that has been linked to a disruption of melatonin production.
Hetlioz is a melatonin receptor agonist, stimulating production of this hormone. In an open-label, non-controlled study presented at the World Sleep meeting in 2017, parents of 12 Smith-Magenis patients reported better quality sleep and less aberrant behaviour during 28 weeks’ treatment than in an eight-week baseline period.
The pivotal trial has enrolled 48 patients and has a crossover design. The primary endpoints measure improvements in sleep parameters and clinical global impression severity scale at 21 weeks, versus placebo. If it is positive Vanda could file an sNDA in 2019 and launch in 2020.
Meanwhile, the NK1 antagonist tradipitant is already in a phase III trial in atopic dermatitis, with readout expected next year, but the phase II data in gastroparesis could stimulate investors. The phase II trial tests it against placebo in 150 patients, measuring reduction in nausea at four weeks from baseline using the gastroparesis cardinal symptoms index.
Stifel analyst Derek Archila believes that physicians will likely view a nausea reduction of greater than one point, and a 20% improvement in nausea-free days, as clinically meaningful. Hetlioz has 2024 forecast sales of $265m and tradipitant $292m, according to EvaluatePharma’s sellside consensus.
Evofem Biosciences’ first attempt to get US approval for its topical contraceptive foundered when the FDA decided that results from the part of the trial conducted in Russia could not be generalised to the US population. The application was rejected in spring 2016, and the company swung straight into enrolling a wholly US-based phase III trial. This study, Ampower, ought to yield topline data by the end of this year.
Amphora is a gel formulation of L-lactic acid, citric acid and potassium bitartrate. Evofem refers to it as a multipurpose vaginal pH regulator; it is designed to keep vaginal pH within the normal range of 3.5 to 4.5, an acidic environment inhospitable to sperm and certain viral and bacterial pathogens, the company says. It is being developed as a form of non-hormonal, non-systemic birth control, as well as for the prevention of certain sexually transmitted infections.
The Ampower trial, also called AMP002, is testing it in the former setting, and has enrolled 1,350 women aged between 18 and 35. The primary endpoint of the six-month trial measures the number of women who become pregnant. The secondary endpoint is the incidence of adverse events, and sexual function will also be assessed.
Unlike the first phase III trial, the 3,000-strong AMP001, Ampower does not have a control group. The FDA told Evofem in late 2016 that a single-arm, non-comparative study would be sufficient to address the deficiencies in the initial application.
Assuming positive results – and to be fair, AMP001 did meet its primary endpoint, according to a filing with the US Securities and Exchange Commission – Evofem will re-submit Amphora’s NDA in the second quarter of 2019. Should the agency capitulate this time, Amphora could go on sale in January 2020.
In AMP001 the six-month cumulative pregnancy rate with Amphora was 4.1% for perfect use and 10.5% for typical use, defined at least one episode of coitus without using the product correctly and without any backup or emergency contraception. The equivalent rates for the pill are approximately 1% and 9%.
Evofem says there was “widespread demand for participation” in Ampower and believes that there is a commercial opportunity for a non-hormonal contraceptive that can, unlike condoms, be controlled by women. But analysts from Cantor Fitzgerald have warned that, if approved, Amphora would represent a new treatment paradigm in contraception, and thus driving adoption will require educating patients.
|Hetlioz||Sleep disturbance in Smith-Magenis syndrome||NCT02231008|
|Amphora||Russian and US-based phase III (AMP001)||NCT01306331|
|Amphora||Confirmatory US-based phase III (Ampower/AMP002)||NCT03243305|