Sumitomo Pharma Co., Ltd.

A new drug combo of enzalutamide and hormone therapy has been shown to extend survival for men with recurring prostate cancer, reducing death risk by over 40%. The study followed more than 1,000 patients worldwide and was led by Cedars-Sinai researchers. Experts call it a game changer that’s likely to reshape treatment guidelines for aggressive prostate cancer. Men whose prostate cancer returns after surgery or radiation therapy may soon benefit from a powerful new treatment that has been shown in clinical trials to reduce the risk of death by more than 40%. Researchers tested a therapy that combines enzalutamide, an existing cancer drug, with standard hormone therapy. This approach significantly lowered death rates among men whose prostate cancer came back after initial treatment and who had few remaining options. The study findings were published in The New England Journal of Medicine (NEJM) and presented at the European Society for Medical Oncology Congress (ESMO) on Oct. 19 in Berlin. "After initial treatment, some patients see their prostate cancer come back in an aggressive way and are at risk for their disease to spread quickly," said Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer and co-principal investigator of the study. "Hormone therapy, which is what we've been offering patients for 30 years, has not improved survival and neither has anything else. That makes these findings a real game changer." The international clinical trial followed more than 1,000 men from 244 medical centers across 17 countries. All participants had high-risk biochemically recurrent prostate cancer, a condition where prostate specific antigen (PSA) levels rise rapidly after surgery or radiation. PSA is a protein used to monitor prostate cancer activity, and a sharp increase after treatment often signals that the disease is likely to return and spread, often to the bones or spine. "We know these patients are at high risk of developing metastatic disease and dying of their cancer unless we offer a meaningful treatment option," said Freedland, professor of Urology and the Warschaw, Robertson, Law Families Chair in Prostate Cancer. Participants were randomly assigned to receive either hormone therapy alone, enzalutamide alone, or both together. After eight years of follow-up, those who received the combination therapy had a 40.3% lower risk of death compared to those in the other two groups, according to Freedland. "This clinical trial, one of many that Cedars-Sinai Cancer has offered to its patients, is an example of the translational work being done by our physician-scientists," said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. "The result will be improved treatment and better outcomes for patients everywhere." Freedland added that enzalutamide is already approved by the Food and Drug Administration and included in National Comprehensive Cancer Network treatment guidelines based on earlier research by the same team. He said these new results will likely strengthen those recommendations and help establish the enzalutamide and hormone therapy combination as the new standard of care for patients with high-risk biochemically recurrent prostate cancer. "These important findings identify a treatment that prolongs survival in men with aggressive prostate cancer," said Hyung Kim, MD, a urologic oncologist and chair of the Department of Urology at Cedars-Sinai. "The latest analysis complements previous studies that found enzalutamide significantly improved survival in other prostate cancer settings, and will change how we take care of our patients." Funding: The study was sponsored by Pfizer Inc. and Astellas Pharma Inc., the co-developers of enzalutamide. Disclosures: Stephen J. Freedland reports being a consultant to Astellas Pharma Inc., AstraZeneca, Bayer, Eli Lilly, Johnson & Johnson Innovative Medicine (formerly Janssen), Merck, Novartis, Pfizer Inc., Sanofi, Sumitomo Pharma America, Inc. (formerly Myovant Sciences, Inc.), and Tolmar.

A respiratory biotech that launched Tuesday morning aims to take advantage of excitement in COPD drug development spurred by two recent deals. AeroRx Therapeutics took the wraps off a $21 million Series A that it’s using to get its lead program through Phase 2b testing in chronic obstructive pulmonary disease, or COPD. It’s the same category that spurred Merck’s $10 billion acquisition of Verona Pharma and GSK’s partnership with Hengrui Pharma that could be worth $12 billion if everything pans out. The AeroRx drug, known as AERO-007, is a nebulized reformulation of two approved compounds — indacaterol and glycopyrrolate — that use different mechanisms of action. Indacaterol is a long-acting beta agonist (LABA), while glycopyrrolate is a long-acting muscarinic agonist (LAMA). Combining LABAs and LAMAs is common when treating COPD. AeroRx CEO Ahmet Tutuncu said the FDA has approved five such products. An inhaler combination of indacaterol and glycopyrrolate was approved in 2015 as Utibron, which was developed by Novartis and out-licensed to Sunovion Pharmaceuticals a year later. (Sunovion is now owned by Sumitomo Pharma.) All the approvals are for inhalers with dry powder, which is more difficult for older and sicker patients to use, Tutuncu said. AeroRx believes it can be the first company to offer a nebulized formulation as a first-line maintenance therapy in COPD. “It’s a different delivery technology, or full dose delivery, for those patients who need to be on nebulized medicines,” Tutuncu said. “A significant number of COPD patients who are typically getting older, they are on inhalers, but they are the ones who end up in hospitals with exacerbations for symptom control, and therefore they need to be on nebulized medicine.” So far, AeroRx has run a small Phase 2a study with 16 patients that suggested AERO-007 could be dosed once daily. In the Phase 2b trial, researchers plan to test once-daily and twice-daily doses. Most other details about the trial remain undisclosed until after discussions with the FDA, according to Tutuncu, including how long it’s expected to last. But because both components of AERO-007 are already approved, Tutuncu expects an “abbreviated” late-stage development process comprising the Phase 2b and Phase 3 trials. The trials will also enroll all COPD patients, and if AERO-007 wins approval, AeroRx plans to market it for patients older than 65 years old. The company also has another preclinical program called AERO-111, which is a triple combination nebulized COPD treatment. (There are two approved triple-combo inhalers.) In addition to a LABA and LAMA compound, AERO-111 also includes a corticosteroid. Tutuncu said the company is still figuring out which one to use. AeroRx’s Series A comes about 18 months after it closed a $6 million seed round in the spring of last year. With the new cash in hand, AeroRx is aiming to capitalize on the recent momentum in COPD following the Merck and GSK deals. “Those were two really important validation points for the interest from big pharma for nebulized delivery in the respiratory space, and particularly in the COPD space,” Tutuncu said. “We’re very excited about that potential for collaboration with pharma down the road.”

Frankfurt: Bayer 's pioneering cell and gene therapies for Parkinson's disease are at the forefront of an exciting but risky test of CEO Bill Anderson's development credentials as patent expiries on blockbuster drugs threaten the group's long-term growth projects. Rivals in cell and gene therapy technologies are already generating revenue from treating cancer or rare hereditary diseases, but Bayer is entering new territory through subsidiary BlueRock's bemdaneprocel, an experimental Parkinson's disease treatment designed to replace dopamine-producing brain cells killed by the disease. BlueRock reached a milestone on Monday, becoming the first to take a cell therapy against Parkinson's to the third phase of testing, but the path to regulatory approval is long and the outcome uncertain. Pharma division head Stefan Oelrich expects results in 2028 or 2029. PIPELINE CHALLENGES FOR CEO Former Roche executive Anderson, meanwhile, is coming under increasing scrutiny over Bayer's pharmaceuticals pipeline after the revenue hit it has taken from the expiry of patents on its anticoagulant Xarelto and eye medicine Eylea. That leaves cell and gene therapies accounting for about 20% of a pharma pipeline Anderson identified as one of the biggest challenges facing the German conglomerate when he took the helm in June 2023. "Anderson's background is in the pharmaceutical business. After more than two years, it's about time he started to deliver in his strongest domain," said Ingo Speich, at mutual funds company Deka Investment. "Bayer urgently needs success in the pharmaceutical sector to overcome past disappointments and rebuild trust in the capital market." Markus Manns at Union Investment also emphasised the risk element. "Bayer's cell and gene therapies do not currently play a role in the valuation of the group due to the high development risk," he said, citing the complexity of transplanting cells into the brain and the immune suppression patients will require. The development line-up took a big hit in 2023, when a once-promising blood thinner flopped in a trial, though cancer drug Nubeqa and kidney disease medicine Kerendia are compensating for lost Xarelto sales. SHARES DOWN 70% SINCE MONSANTO DEAL Bayer's problems run deeper, however, with its shares down more than 70% since the 2018 takeover of Monsanto. U.S. litigation over disputed claims that its weedkiller glyphosate causes cancer has cost it billions of dollars, with billions more at stake as further settlements loom. The group's heavy debt burden, meanwhile, has led it to consider a capital increase in the medium term. Much rests on the cell and gene therapies, therefore. Despite bemdaneprocel being years from market launch, Bayer is working on a manufacturing network for cell and gene therapy products, including a $250 million facility in California. "The manufacture of cell and gene therapy products is not just a science, it is a very special kind of expertise," says Bayer's Oelrich. "That's why we use the term 'the process is the product' in cell and gene therapies." Though there is no analyst consensus yet on future sales potential and Bayer has not issued estimates on sales or costs, the rewards could be considerable. "We believe that our treatments can stop the progression of the disease and possibly reverse it," said Christian Rommel, Bayer's head of pharmaceutical research and development. Parkinson's disease and its progressive brain damage affect more than 10 million people worldwide, with the number projected to more than double by 2050. Symptoms include loss of muscle control, tremors and dementia in some patients. Christie Wong, neurology expert at market researcher GlobalData, said that treatment of the causes rather than the symptoms of the disease would be in high demand. "The need for disease-modifying therapies is one of the greatest unmet needs in this area," she said. WIDE FIELD OF RIVAL PROJECTS The hunt for Parkinson's treatments has suffered many setbacks over the years, but there has been something of a revival of late. Market researchers at GlobalData told Reuters that Bayer's BlueRock is the most advanced in a race of 17 projects testing cell therapies against Parkinson's. They also estimate that the overall Parkinson's therapy market will reach $7 billion in the world's seven largest markets by 2033, almost doubling from 2023, on new therapy launches and growing patient numbers. Bayer's rivals in the field include Japan's Sumitomo Pharma in partnership with Kyoto University Hospital, a collaboration between Lund University and Cambridge University as well as U.S. biotech company Aspen Neuroscience. Among Bayer's other cell and gene therapy projects, its AskBio operation is in separate Phase II testing of new gene therapies for Parkinson's disease and heart failure. The broader cell and gene therapy sector is expected to climb from $8.3 billion in 2024 to $71.7 billion in 2030, GlobalData says. (Reporting by Patricia Weiss Writing by Ludwig Burger Editing by David Goodman)