KaNDy Therapeutics Ltd.

Astellas’ headquarters for the Americas iStock, JHVEPhoto One patient developed elevated liver blood tests after receiving Astellas Pharma’s non-hormonal small molecule blocker, leading the regulator to add a warning to the drug’s label. The FDA on Thursday added a warning to the label of Astellas Pharma ’s hot flash therapy Veozah (fezolinetant), alerting patients and prescribers to a newly documented risk of “rare but serious” liver injury. The new warning was prompted by a postmarketing review of a patient who was taking Veozah and subsequently saw spikes in liver blood test values. The patient also showed signs of liver injury after being treated for around 40 days, according to the regulator. Per Veozah’s updated label , prescribers should test their patients’ blood liver markers more frequently, including monthly screens for the first two months after initiating Veozah, followed by additional tests after three, six and nine months. Doctors and prescribers should also conduct hepatic testing before starting patients on Veozah. In case of signs that could indicate liver problems, patients should stop taking Veozah “immediately” and contact their healthcare professional, according to the FDA. Common symptoms of liver harm include fatigue, jaundice, nausea and vomiting, as well as unusual itching and light-colored stools. Despite being a hit to Veozah’s safety profile, Thursday’s label seems unlikely to substantially hurt Astellas. Jeffries analysts in a note to investors said that the new warning “strengthened Veozah’s label” and that while the additional testing requirements will put more burden on patients, they “may not have much impact on demand overall.” Administered orally, Veozah is a non-hormonal small molecule blocker of the NK3 receptor which plays a part in the signaling cascade that results in the release of specific hormones involved in the menstrual cycle. Veozah specifically acts on neurons in the brain’s thermoregulatory centers, allowing it to reduce the frequency and intensity of hot flashes and night sweats. The FDA approved Veozah in May 2023 for women in menopause. In December 2023, Astellas unveiled more Phase IIIb data for Veozah, touting statistically significant improvements in moderate to severe vasomotor symptoms in patients at 24 weeks compared with placebo. Veozah also reduced sleep disturbance in these patients. At the time, the pharma noted that these findings will help it with reimbursement negotiations in Europe. Bayer is also advancing a non-hormonal competitor to Veozah. Elinzanetant is a small molecule dual inhibitor of the NK1 and NK3 receptors, which the pharma is also positioning as a treatment for moderate to severe vasomotor symptoms in menopause. Bayer won rights to elinzanetant when it bought KaNDy Therapeutics in August 2020 for $425 million upfront . In May 2024, Bayer reported data from its pivotal Phase III OASIS 1 and OASIS 2 studies, demonstrating that elinzanetant significantly lowered the frequency of hot flashes, reduced sleep disturbances and improved menopause-related quality of life.

Bayer's work to file for approval of elinzanetant is "running at full steam.” Bayer’s master plan for its OASIS program is coming together, with the German drugmaker posting phase 3 data that suggest it could challenge Astellas for a recently unlocked menopause market.  The phase 3 data come from the OASIS 1 and 2 studies. Bayer reported the success of the trials in January, and followed up with news of a hit on a third study in March, but kept the data to itself. With Astellas’ Veozah authorized in the treatment of hot flashes associated with menopause, the details will matter if Bayer wins approval for elinzanetant and starts trying to claim a piece of the market.  Bayer used the 2024 American College of Obstetricians and Gynecologists annual meeting to reveal the data behind the hits on the co-primary endpoints. Both studies looked at the effect of elinzanetant on the severity and frequency of hot flashes after four weeks and 12 weeks of oral daily doses.  In OASIS 1, Bayer reported mean reductions versus placebo in the frequency of hot flashes of 3.29 at Week 4 and 3.22 at Week 12. The Week 4 and Week 12 reductions in frequency in OASIS 2 were 3.04 and 3.24, respectively. Astellas won approval on the strength of phase 3 trials that linked Veozah to placebo-adjusted reductions (PDF) in hot flash frequency of 2.1 and 2.6 at week 4 and 2.6 and 2.5 at week 12. Comparing data across different clinical trials can give misleading impressions but the available evidence suggests Bayer could be competitive. Across OASIS 1 and 2, Bayer reported mean reductions versus placebo for severity of 0.33 and 0.22 at Week 4 and 0.40 and 0.28 at Week 12. Astellas reported placebo-adjusted reductions in severity of 0.2 and 0.3 at both Week 4 and Week 12.   Sleep is an area in which elinzanetant may have an edge over Astellas’ neurokinin-3 (NK-3) antagonist Veozah. Elinzanetant acts on both NK-3 and NK-1, a related receptor that research suggests may have effects on insomnia and mood unrelated to menopause. Bayer reported statistically significant improvements in sleep disturbances and menopause-related quality of life. Astellas has also posted positive sleep data. With three phase 3 successes under its belt, Bayer is preparing to file for approval of elinzanetant. Bayer CEO Bill Anderson said “preparations to obtain first market authorizations are running at full steam” on an earnings call this week. The molecule, which Bayer acquired in its KaNDy Therapeutics buyout, is part of a thin late-phase pipeline that needs to offset anticipated generic erosion of Eylea and Xarelto sales.

New data from two late-stage studies of an experimental Bayer drug show it reduced the frequency and severity of common symptoms of menopause, supporting the companys case for seeking regulatory approval.The results were disclosed by Bayer Thursday and will be presented at this years annual meeting of the American College of Obstetricians and Gynecologists in San Francisco.Bayer shared the trials success in January, but didnt reveal specific findings. The company also announced positive results from a third Phase 3 study in March, when it confirmed plans to file for marketing authorization of the drug.Known as elinzanetant, Bayers drug would, if approved, compete with a medicine from Astellas called Veozah, which is approved in the U.S. to treat moderate-to-severe vasomotor symptoms caused by menopause.Often described as hot flashes, vasomotor symptoms commonly occur during menopause, the natural period when a womans menstrual cycle stops. Caused by the resulting decrease in estrogen levels, symptoms can last for many years and are severe for some women.Hormonal therapies are sometimes used to treat vasomotor symptoms, but they may increase the risk of heart attacks, blood clots and breast cancer. The Food and Drug Administration recommends that, if prescribed, hormone therapies be taken at the lowest dose and for as short a time as possible.There are limited approved non-hormonal treatments for bothersome menopausal symptoms, such as hot flashes and sleep disturbances, said JoAnn Pinkerton, professor and director of midlife health at UVA Health, in a statement provided by Bayer. Consequently, many women experience discomfort for months or even years, with the majority of symptoms left untreated.With its approval last year, Veozah became the first drug that works by blocking a protein known as neurokinin 3, or NK3, thats involved in regulating body temperature.Bayers drug works along the same lines. Also a neurokinin receptor antagonist, elinzanetant targets the NK1 and NK3 receptors.In the Oasis 1 and Oasis 2 studies, Bayer respectively enrolled 396 and 400 postmenopausal women between the ages of 40 and 65 years with moderate to severe vasomotor symptoms. Women either received a once-daily dose of elinzanetant or placebo, and were evaluated over 26 weeks.From Oasis 1, Bayer reported treatment led to an average reduction of 3.29 occurrences of vasomotor symptoms at week 4, and of 3.22 at week 12, as recorded by a hot flash daily diary. The reductions Bayer reported are adjusted for placebo, a spokesperson confirmed. Significant decreases in symptom severity were also reported at weeks 4 and 12, compared to placebo.In Oasis 2, elinzanetant treatment reduced the frequency of symptom occurrence by an average of 3.04 at week 4 and by 3.24 at week 12. Participants in this study also reported significant lessening of severity, compared to those on placebo.Bayer added that women in the studies reported improvement in sleep disturbances and in menopause-related quality of life.In the two studies Astellas used to support Veozahs approval, its drug led to placebo-adjusted reductions in the frequency of vasomotor symptoms by an average of 2.5 and 2.6 at week 12.Oasis 3, the study Bayer in March said succeeded, is evaluating elinzanetant in 628 postmenopausal women over 52 weeks. The company hasnt yet detailed its findings in full, but said treatment similarly led to significant declines in the frequency of symptoms, compared to placebo.Headache and fatigue were the most commonly reported side effects associated with treatment among those given elinzanetant, Bayer said.These results ... build on our confidence that elinzanetant may be a potential non-hormonal solution for [women], said Pinkerton.Bayer acquired the rights to elinzanetant via a $425 million buyout of biotechnology company KaNDy Therapeutics in 2020. In a March presentation, Bayers head of its pharmaceutical division Stefan Oelrich described the drug as a potential blockbuster.However, it might face an uphill commercial battle in competing with Veozah. Astellas has reported low demand and difficulty securing insurer reimbursement.Bayer plans to submit data from the three Oasis studies in the coming months. '