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Cancer is well represented in the Astellas Pharma portfolio and pipeline, but the drugmaker has made diversification a key part of its growth strategy. Newer products in its drug lineup include a vision-loss disorder drug and a first-in-class therapy for menopause symptoms. Cell and gene therapies are also a key part of Astellas’s growth strategy, building off of its 2020 acquisition of gene therapy developer Audentes Therapeutics. Within gene therapy, the Tokyo-based company is focused neuromuscular disorders, Chief Medical Officer Tadaaki Taniguci said in an interview last week during the annual J.P Morgan Healthcare Conference in San Francisco. “Our strategy in the past is more developing our capability,” Taniguci said. “We actually acquired Audentes, developing our capabilities toward gene therapy. But now we see that the more important thing for us is to really bring in clinical-phase assets to our pipeline.” Exclusive Improving the Healthcare Financial Experience to Help Care Flow Zelis CEO Amanda Eisel shares her perspective on how the company is solving the problems of a fragmented health financial system to benefit all. By Stephanie Baum The Astellas pipeline is split nearly 50/50 between internally developed drug candidates and assets from acquisitions or external collaborations. Audentes brought AT132, a gene therapy for the rare neuromuscular disease X-linked myotubular myopathy. This program has been beset by setbacks due to patient deaths in the trial. But Audentes also brought programs for two rare other rare disorders, Pompe disease, an inherited disorder that leads to muscle weakness, as well as Friedreich’s ataxia, which causes cardiomyopathy. Both programs are in early clinical development. Astellas is still expanding its gene therapy prospects through deals. Last October, the company paid AviadoBio $50 million for the option to license the biotech’s lead gene therapy, which is in early clinical development for frontotemporal dementia, a neurodegenerative disorder with no FDA-approved treatments. The deal structure is similar to a 2022 agreement that gave Astellas the option to license a Taysha Gene Therapies program for Rett syndrome, a disorder that leads to developmental problems. Phase 1/2 safety and efficacy data for this Rett therapy, TSHA-102, are expected in the first half of this year. Astellas remains willing to strike deals that give it new tools that expand its capabilities in gene therapy, Taniguci said. The company is already developing gene therapies delivered to their bodily destinations carried aboard adeno-associated viruses (AAV). These engineered viruses preferentially go to the liver. In 2021, Astellas began a research collaboration with Dyno Therapeutics focused on discovering novel capsids — the protein shells that envelop a genetic payload — for delivery to skeletal and cardiac muscle. Last month, Astellas began a partnership with Sangamo Therapeutics, securing the right to use one of that biotech’s proprietary capsids to penetrate the brain and reach neuronal targets, which Taniguci said fits with his company’s neuromuscular disease strategy. Penetrating the blood-brain barrier “is the one biggest challenge to overcome to target the [central nervous system],” he said. “So they help us to create much better access to the target organ. We see more platform development together with them to actually create the next generation of gene therapy.” Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech In oncology, the company’s top products are Xtandi, a small molecule drug for prostate cancer, and Padcev, an antibody drug conjugate for bladder cancer. A Phase 3 study is evaluating Padcev in combination with the Merck immunotherapy Keytruda as a treatment for muscle-invasive bladder cancer. Data are expected in Astellas’s next fiscal year, which starts on April 1. Additional clinical studies are testing Padcev in non-muscle-invasive bladder cancer and other solid tumors. Astellas is pursuing other approaches to cancer. Its in-house R&D has yielded ASP3082, the company’s lead targeted protein degrader drug for cancer. This drug candidate targets the cancer-driving protein KRAS G12D. At the European Society of Medical Oncology (ESMO) meeting last September, Astellas reported preliminary Phase 1 data showing anti-tumor activity in patients with pancreatic, colorectal, and non-small cell lung cancers. Taniguci noted the results indicate a dose-dependent degradation of the target protein. Astellas will need to show differentiation from other companies developing KRAS G12D-targeting drugs, such as Revolution Medicines and Bristol Myers Squibb, via the pharma giant’s acquisition of Mirati Therapeutics. But Astellas envisions potentially bringing its targeted protein degradation approach to multiple KRAS mutations. “This is a new technology that we started using for KRAS G12D, but we also have a pan-KRAS product coming to the clinic pretty soon,” Taniguci said. “We also started expanding more to other targets. We cannot disclose yet, but [there’s] a lot of excitement.” Astellas’s newest cancer drug is Vyloy, which in October became the first FDA-approved drug targeting claudin 18.2, a protein highly expressed in gastrointestinal cancers. This internally developed drug is a monoclonal antibody. The Astellas pipeline includes another program targeting claudin 18.2, but with a bispecific antibody. This program, ASP2138, is in Phase 1 testing. Women’s health is a newer piece of Astellas’s portfolio coming with the 2023 FDA approval of Veozah, a non-hormonal drug for treating vasomotor symptoms caused by menopause. The first-in-class therapy is a small molecule designed to block neurokinin 3, a receptor that plays a role in regulating body temperature. Last month, the FDA added a black box warning on the product’s label, flagging the risk of severe liver injury. Taniguci said liver toxicity is a known risk that was first observed in clinical trials. None of those cases were severe. In the market, the product has been used by about 100,000 patients. “Liver tox is relatively rare, but sometimes we see the severe cases,” Taniguci said. “That’s why I think it’s important to provide cautions for the patient and physician to use this important medicine. But of course we believe that the benefit/risk balance is really positive. So that’s why we still hear a lot of patients willing to use Veozah in treatment of [vasomotor symptoms].”

As Bayer awaits an FDA decision on its non-hormonal treatment for hot flashes caused by menopause, the company is unveiling new results in a slightly different patient population: women whose hot flashes were caused by breast cancer therapy. The company said its experimental drug elinzanetant met all the primary and secondary endpoints in a Phase 3 trial enrolling women whose vasomotor symptoms — more commonly known as hot flashes — are caused by adjuvant endocrine therapy. Bayer has yet to report any hard data but said elinzanetant reduced both the frequency and severity of symptoms at weeks 4 and 12. Adjuvant endocrine therapy is standard treatment for many breast cancer patients that can come with hot flashes as a side effect. In addition to improving symptoms, Bayer said the data suggest elinzanetant helped patients get better sleep compared to placebo. The company expects an FDA decision for menopause-related hot flashes in the second half of 2025. In that setting, elinzanetant will compete with Astellas’ Veozah, which was approved by the FDA in May 2023 and works in a similar fashion. Veozah targets a receptor called neurokinin 3, or NK3, which is involved in the brain’s regulation of body temperature. Bayer’s elinzanetant also targets NK3, as well as another receptor called NK1. Veozah had a sluggish commercial launch, generating 7.3 billion yen in 2023 ($46 million) compared to the company’s initial projections of 53 billion yen ($335 million). Executives have cited insurance coverage as a key hurdle, but noted during Astellas’ most recent earnings call in October that “prescriptions are continuing their upward trend,” according to an AlphaSense transcript. The company raised its Veozah sales projections for its fiscal year 2024, which ends in March. The FDA also added a boxed warning , its most serious warning, to Veozah’s label in December over a risk of “risk of rare but serious liver injury.” The update was triggered by a patient whose signs and symptoms of liver injury were reported to the FDA’s adverse event reporting system post-launch. After stopping treatment, the FDA said the patient’s symptoms “gradually went away,” and their blood tests returned to normal. A Bayer spokesperson told Endpoints News that to date, “clinical evaluation has not indicated any statistically significant liver safety concerns for elinzanetant.” The company said safety in the latest study was “generally consistent with previously conducted studies and published data on elinzanetant in postmenopausal women with VMS.” Astellas launched a Phase 3 trial in August studying women who experience hot flashes related to breast cancer treatment.