NKX3-1

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.

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 has unveiled detailed data from two pivotal trials of its investigational menopause drug elinzanetant, setting the stage for a heated commercial battle with Astellas' already approved Veozah (fezolinetant) in the long-neglected vasomotor symptoms (VMS) market.At the American College of Obstetricians and Gynecologists (ACOG) annual meeting, Bayer presented detailed results from the OASIS 1 and 2 studies, demonstrating that the dual neurokinin-1,3 (NK-1,3) receptor antagonist significantly reduced the frequency and severity of moderate-to-severe hot flashes associated with menopause. A total of about 800 post-menopausal women were enrolled across the two studies.Stacking up to VeozahIn OASIS 1, elinzanetant showed significant mean reductions versus placebo in hot flash frequency of 3.29 at week 4 and 3.22 at week 12. For severity, the reductions were 0.33 and 0.40 at those timepoints, respectively.OASIS 2 yielded similar results, with elinzanetant demonstrating significant mean reductions in frequency of 3.04 at week 4 and 3.24 at week 12, and in severity of 0.22 and 0.29, respectively.The data could position elinzanetant as a strong competitor to Veozah, an NK-3 receptor antagonist approved last year for the treatment of VMS. It is also cleared in Europe under the name Veoza. In the SKYLIGHT 1 and SKYLIGHT 2 trials, Astellas' drug reduced hot flash frequency by 2.07 and 2.55 at week 4 and by 2.53 and 2.55 at week 12. Hot flash severity reductions were about 0.20 and 0.29 across the two SKYLIGHT studies, respectively.While efficacy data suggest a closely matched rivalry, other factors could tilt the scales. Bayer said elinzanetant also met key secondary endpoints in OASIS 1 and 2, significantly improving sleep compared to placebo. Mean change from baseline to week 12 on the PROMIS sleep disturbance measure was 5.58 in OASIS 1 and 4.32 in OSAIS 2 in favour of elinzanetant over placebo.No liver injuryStudy drop-outs due to adverse events were higher in the elinzanetant arms than placebo in both studies (8.5% vs 6.7% in OASIS 1; 6.5% vs 2% in OASIS 2).Liver safety has also been a point of concern for Veozah, which requires liver function testing due to possible increases in hepatic serum transaminase levels. However, researchers said there were "no cases of drug-induced liver injury causally related to elinzanetant" or any incidences of endometrial hyperplasia or malignant neoplasm in either of the OASIS studies, according to the ACOG presentations.In a recent interview with FirstWord, Waljit Dhillo, professor of endocrinology and metabolism at Imperial College London, said "it would definitely be a big difference" if elinzanetant avoids such liver monitoring requirements. "If you can just give a tablet and then go away, that would be attractive."Hitting the NK1 receptor could theoretically provide elinzanetant with better liver safety and less sleep disturbance compared to Veozah, which only targets NK3. However, when asked how optimistic he was about whether elinzanetant could necessitate less liver monitoring, Dhillo noted that since there are no NK3 receptors in the liver, any differentiation in liver safety may come down to differences in the specific molecules rather than their receptor targets.FirstWord recently caught up with Astellas leadership to discuss Veozah, including the concerns regarding liver safety. For more on that interview, see – ViewPoints: Having broken ground in untapped menopause market, Astellas outlines strategy for Veozah as competition heats up.First-mover advantage?"The robust efficacy and favourable safety profile of elinzanetant reinforces its potential as a non-hormonal treatment for women experiencing menopause," said Bayer's R&D head Christian Rommel in a company release. Bayer plans to submit elinzanetant's data to regulatory authorities for marketing approval this year, setting up a commercial clash with Astellas' first-mover advantage. "Our preparations to obtain first-market authorisations are running at full steam," Bayer CEO Bill Anderson stated at the company's earning call this week.Bayer would not disclose elinzanetant's price until the FDA clears it, although some analysts suggest it could cost as much as or more than Veozah, which can cost at least $550 for a month's supply.Commenting on the OASIS readouts, Morgan Stanley analysts said that "although elinzanetant appears slightly more effective than Veozah in reducing symptom frequency over 12 weeks, we do not think this will make a big difference in terms of business. Bayer is due to launch the drug in 2025, giving Veozah a two-year advantage."