LONDON – Kandy Therapeutics Ltd. has announced positive results for its nonhormonal treatment for menopause symptoms, showing a reduction in the number of hot flashes and night sweats, and a positive effect on secondary endpoints relating to mood and quality of life.
Unlike hormone replacement therapy, which can take weeks to reduce vasomotor symptoms, NT-814, a dual inhibitor of the neurokinin 1 and 3 receptors in the hypothalamus, had an almost immediate effect.
“The phase IIb was effective in a way we hoped for but never really expected. There was a highly significant reduction in hot flashes and night sweats,” Mary Kerr, Kandy’s CEO, told BioWorld.
“What is also exciting is the effect on mood, sleep and general quality of life. It’s unique to see this constellation of effects in such a short period of time,” she said.
Kerr will be presenting the headline data at the Biotech Showcase in San Francisco on Tuesday. Full results will be presented at medical conferences.
In the trial, reductions in the frequency of hot flashes started during the first week of treatment. By week four there was an average reduction of minus 6.7 hot flashes per day for NT-814 vs. 2.7 fewer for placebo (p<0.0001). By the end of the trial at week 12, the active arm experienced an average of 7.8 fewer hot flashes per day vs.4.7 fewer for placebo (p=0.0092).
There also were marked improvements in the secondary endpoints of quality of life, mood and sleep quality. NT-814 was well-tolerated across the dose range.
The trial recruited 199 women in Canada, the U.S. and the U.K., who were experiencing at least seven hot flashes per day. They were randomized to receive one of four doses of NK-814 or placebo. Subjects completed electronic diaries for two weeks before and during the study.
Kandy is now turning its attention to phase III development. Kerr said it is not possible to say what the timelines will be at this stage. Apart from FDA and EMA approval for the study, the Stevenage U.K.-based company has to raise the money, and is exploring a potential private round, an IPO or a pharma partnership.
NT-814 began life at Glaxosmithkline plc and was spun out into Nerre Therapeutics Ltd. (of which Kerr is also CEO) in 2012, when the pharma company moved out of neuroscience. The drug subsequently was moved again when Kandy was set up as women’s health specialist at the end of 2016.
At that point, venture capital investors did not want to fund women’s health products because pharmaceutical companies were not interested in that area. Since then, the picture has changed somewhat, Kerr said.
For example, Bayer AG last week announced a five-year collaboration with drug discovery specialist Evotec AG in polycystic ovary syndrome, having previously completed a similar joint discovery project in endometriosis.
Similarly, last November, Johnson & Johnson Innovation, the company’s channel for accessing external science, announced an agreement with London-based Founders Factory, a specialist in building startups on behalf of large corporate partners. Under the deal, Founders Factory will set up an incubator in New York to create and grow 35 companies over the next five years, with a particular focus on women’s health.
Kerr also cited Abbvie Inc.’s recently approved Orilissa (elagolix), for managing endometriosis and heavy menstrual bleeding caused by uterine fibroids. The pharma company has made benign gynecologic diseases a strategic priority for 2020, including exploring novel clinical applications of Orilissa, and forecasts sales of the product will be $2 billion-plus by 2025.
Alongside the increasing interest in women’s health, Kerr said she thinks there is enduring demand for products that address unmet needs in primary care.
Orally available NK-814 works by blocking estrogen-sensitive neurons in the hypothalamus that become dysregulated due to the absence of estrogen following menopause.
In terms of nonhormonal approaches to relieving vasomotor symptoms, the main competitor to NK-814 is fezolinetant, Astellas Pharma Inc.’s neurkinin-1 antagonist, acquired when it bought Ogeda SA of Gosselies, Belgium, in a deal with a total value of $850 million, in April 2017.
Fezolinetant began a phase III development program last August, in which it is planned to recruit around 2,000 women.
Although NK-814 is further behind in development, Kerr said she thinks there are benefits in having an advance party staking the ground with regulators. She also believes the dual effect of inhibiting NK-1 as well as NK-3 is an important differentiator between the two products.
NK-3 is involved in thermoregulation while NK-1 addresses sleep disturbance. Fezolinetant has shown similar efficacy to NT-814 in controlling hot flashes, but Kerr noted, Astellas has not published any data on secondary endpoints relating to sleep and mood.
The NT-814 phase IIb trial is the first to show effects on vasomotor symptoms and secondary endpoints relating to quality of life, sleep quality and mood “together in a single study,” she said.