Fam-trastuzumab deruxtecan-NXKI

New drugs, however heralded, take time to embed into clinical care.Enhertu, the powerful antibody-drug conjugate from Daiichi Sankyo and AstraZeneca, was first approved in the U.S. in 2019, before the world had even heard of a novel coronavirus. This past weekend, results presented at the American Society of Clinical Oncologys annual meeting showed its potential for use in the first-line treatment of metastatic breast cancer, the result of steady work by its makers to test it in earlier and more widely.Immunotherapies like Opdivo, Tecentriq and Imfinzi were first approved eight to 10 years ago. Now, after marching up through metastatic treatment of various tumors, data at ASCO demonstrated how they can be used more widely both before and after surgery in early cancer.And bispecific antibodies, a relatively recent addition to physicians treatment tool kit, are slowly being absorbed into practice, with some tinkering to manage their side effects. Likely a few of the experimental drugs featured over the past few days at ASCO, such as camizestrant or vepdegestrant, will go on to win approval in the years ahead.Gauging which of these data are truly practice-changing is best left for future meetings, but the BioPharma Dive team nonetheless has a few reflections after attending this years. Read on for three of our takeaways:Positive breast cancer data comes with caveatsThis year, ASCO was headlined by promising clinical trial results for several new breast cancer drugs.Enhertu could change the frontline standard of care for an aggressive kind of metastatic breast cancer. Vepdegestrant, an experimental targeted medicine, may help control tumor growth in a common type. And camizestrant, also from AstraZeneca, proved effective at sustaining the benefit patients with that more common tumor experience on first-line therapy.Across the board, we have practice changing data that were presented for every sub-type of breast cancer, which is really exciting said Nancy Chan, a medical oncologist specializing in breast cancer at the NYU Langone Perlmutter Cancer Center.There are important qualifications to the good news, however. Enhertu showed strong benefit as part of first-line treatment for metastatic tumors that are positive for a protein called HER2. But it comes with a dangerous side effect that may make doctors cautious about adoption if its approved in this setting. Moving Enhertu earlier also raises questions about what to use afterwards, since the ADC plays an important role in second-line treatment currently.Vepdegestant, a pill, has promise treating breast cancer patients whose tumors are estrogen receptor positive but lack the HER2 protein. Its efficacy over the common therapy fulvestrant was limited to only patients with mutations in a gene called ESR1, though; those patients without one didnt appear to benefit.A physician interviewed by Cantor Fitzgerald analyst Li Watsek's team was disappointed the drug “didn't show greater differentiation, Watsek wrote in a Monday note to clients.Adding camizestrant into clinical practice, meanwhile, will require greater adoption of a blood test used to monitor for those ESR1 mutations, which doctors fear may be costly and arduous.Still, the data presented should give doctors more options for controlling advanced breast cancer. And they may offer advantages important to patients, too. It's not a small change to remove the intramuscular injection of fulvestrant and change to oral,“ said Chan, about the vepdegestrant data. “That gives the patient back so much more control and significantly improves their quality of life.“ Ned Pagliarulo, Delilah AlvaradoBispecific drugs need troubleshootingIn just a few years, bispecific antibodies have gone from exciting innovation to a common part of clinical practice, used to treat not only late-stage blood cancers but also earlier-stage disease in some tumors. A whole cohort of new ones are in testing, making the field an active area of pharma dealmaking.But they carry immune-related side effects that were previously only seen with complex CAR-T cell therapies. Physicians must now also weigh those risks for a broader group of patients than before. Because theyre meant to be given as outpatient treatment CAR-Ts are often administered in a hospital some oncologists are cautious about using them, fearing patients may not be able to receive hospital care before the side effects they might experience cause serious illness or death.The specific conditions are known as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, both aggressive responses resulting from the activation of immune cells. In the case of Amgens newly launched lung cancer drug Imdelltra, a little more than half of study participants had CRS, usually after the first two doses. Around one in seven had ICANS, usually within the first 30 days, Abdul Rafeh Naqash, immuno-oncology director at the University of Oklahomas Stephenson Cancer Center, said in a panel discussion at ASCO, citing data from a pivotal trial.Melissa Johnson, director of lung cancer research at Sarah Cannon Research Institute, argues Imdelltra can be used outpatient by giving patients monitoring tools like thermometers, blood pressure cuffs and blood-oxygen monitors to detect side effects. The steroid dexamethasone could also be used to tamp down immune response. To reduce hospital stays with CAR-T patients, Sarah Cannon has tested wearable devices that provide continuous monitoring, Johnson said, which could be used for patients on bispecifics, too.There are more bispecifics coming in solid tumor oncology, she said. So we have to grapple with these things now so that we'll be able to give bispecifics for our prostate cancer patients and our breast cancer patients, where the CRS events may be more significant. Jonathan GardnerU.S. science cuts feed undercurrent of alarmASCOs hundreds of sessions were, by and large, concerned with the ins and outs of cancer study data and clinical practice. In that respect, this years meeting was much the same as it always is.But the Trump administrations aggressive downsizing of the federal health workforce and planned curtailment of science spending rippled through the meeting nonetheless.The White Houses budget calls for major reductions in funding for the National Institutes of Health and National Cancer Institute, which could imperil future cancer drug research. ASCO CEO Clifford Hudis used the meetings opening session to warn of the cuts likely impact.We find ourselves in a tragic paradox, he said on Friday. We are living in a time of unprecedented scientific opportunity, yet we are facing historic reductions in the very resources we need to turn these opportunities into hope for millions of patients counting on us.Chan, at the Perlmutter Cancer Center, told BioPharma Dive the effects are already becoming apparent. Across the board, we definitely are seeing a decrease in oncology funding for new ideas and new concepts, both at the clinical level and also at the translational basic sciences level, said Chan. I think that will have a long-term impact.Research that primarily looks at cancers affecting women, and related issues they may experience, could be most at stake. Trump has issued executive orders that target gendered language and DEI programs, potentially raising barriers for researchers seeking federal grant funding to study womens health.Regardless of where you are from in the world, breast cancer is the most common diagnosis in women for most countries, Chan said. This is a common issue for all of us.About one in 12 women will be diagnosed with breast cancer in highly developed countries. It is one of the most studied cancers in the U.S., and data from studies of new treatments were featured across this years meeting. Delilah Alvarado '

CHICAGO Hiroyuki Okuzawa holds an enviable position. The veteran Daiichi Sankyo executive took over as the Japanese drugmakers new CEO two months ago and inherited a company whose cancer medicines have, over the past half-decade, won it three of the pharmaceutical industrys largest licensing deals.One of those medicines, the antibody-drug conjugate Enhertu, again took the spotlightat the American Society of Clinical Oncologys annual meeting here, showing potential to become part of standard therapy for the frontline treatment of advanced breast cancer. It did the same in 2022 and 2024.Okuzawa can point to Enhertu and four other antibody-drug conjugates Daiichi Sankyos developing with AstraZeneca and Merck & Co. as proof of the strength of its research laboratories. By 2030, the company plans to have these five ADCs approved across more than 30 tumor types, which would allow it to treat nearly 400,000 cancer patients each year.Wed like to become one of the most important players in oncology, said Okuzawa, noting aspirations to crack the top 10 companies by cancer drug sales. Our senior leaders are now talking about not only top 10, but maybe top 5. Were very much confident in our ADCs.But, current success notwithstanding, the task ahead of Okuzawa is among the most difficult in corporate management. Daiichi Sankyo has one hit drug platform; he must figure out what comes next.In the coming five years, our growth will be driven by these five programs, he said in an interview at ASCO. But at the same time, we would like to establish the next growth driver. Identifying that driver will be a big part of the companys next five-year plan, which it will launch for the fiscal year beginning next April.Daiichi Sankyos current ADCs are built around a technology known as DXd that the companys scientists have fine-tuned since inventing it 15 years ago. It is the backbone for Enhertu, as well as the recently approved breast cancer medicine Datroway and three other ADCs that remain experimental.ADCs like these contain three main components: a targeting antibody, a cancer-killing toxin and a linking molecule that can tightly hold onto the drugs payload while its transiting through the body, but then release it upon arriving at the tumor. The concept is simple, but the details make the difference in balancing efficacy with safety.Both AstraZeneca and Merck are convinced Daiichi Sankyo has struck the right balance. The former company gave Daiichi Sankyo $1.35 billion in 2019 to license rights to what became Enhertu and then one year later paid another $1 billion upfront for the drug the two companies now sell as Datroway. Then, in 2023, Merck bought rights to the three experimental ADCs for $5.5 billion in payments spread over two years.Daiichi Sankyos next big thing might end up being more ADCs. Okuzawa highlighted two as particularly promising. The first, dubbed DS-3939, combines an antibody licensed from Glycotope with the DXd backbone. It could be an opportunity for Daiichi Sankyo to take on independently, said Okuzawa. The other, DS-9606, uses a new payload technology Daiichi Sankyo hopes will yield other medicines in much the same way DXd has.Yet Okuzawa, who has been at Daiichi Sankyo since 1986 and previously held several senior leadership positions, noted that the companys research may take it in new directions, too. There are a lot of opportunities in the ADC space. On the other hand, [our scientists] are also pursuing discovery research outside of ADCs, he said. We have rich ideas for new modalities.In the meantime, Daiichi Sankyo needs to execute on the partnerships it already has in place with AstraZeneca and Merck. Combined, those deals promise up to $27 billion in conditional fees due upon Daiichi Sankyos medicines reaching certain regulatory and sales milestones. While some of those payments have already been made, the bulk remains unrealized.Enhertu, which earned some $3.7 billion in sales last year, is well on track to meeting expectations. However, the path forward for Datroway and the lead program being developed with Merck may be steeper. While Datroway won an important U.S. approval in January, AstraZeneca and Daiichi Sankyo have narrowed their development plans in lung cancer after obtaining mixed study results. And late last month, Merck and Daiichi Sankyo withdrew an approval application for another ADC in lung cancer after it failed to extend survival in a study they presented Sunday at ASCO.Further biomarker analyses of the [study] are being conducted to determine if certain patient populations might differentially benefit as we explore the path forward for patritumab deruxtecan in lung cancer, a spokesperson for Daiichi Sankyo confirmed by email, using the ADCs generic name.However, we remain confident in the broad clinical development program of patritumab deruxtecan, which includes multiple clinical trials across 15 types of cancer.Development setbacks may be partly to blame for Daiichi Sankyos stock price, which in U.S. over-the-counter trading has fallen by one-quarter over the past year. Shares now trade at just under $26 apiece, about what they were worth at the start of the current five-year planning cycle in 2021.Turning that around may require Okuzawa to navigate Daiichi Sankyo through broader economic challenges, too. The Trump administration is currently investigating whether U.S. importation of pharmaceuticals poses national security risks, a probe that is expected to result in tariffs levied against drugs shipped in from abroad. Its not clear, however, which countries may be targeted.Im concerned that the tariffs could disrupt the global supply chain and may cause drug shortages for U.S. patients, said Okuzawa. We would like to avoid such a situation.Daiichi Sankyo is responsible for supplying both Enhertu and Datroway, and does some of the drugs manufacturing outside of the U.S. The company plans to invest $350 million in building out a plant in Ohio that will be used in ADC production and is considering spending more, according to Okuzawa.We also started internally further discussion to expand the capacity of that New Albany plant to accelerate our ADC manufacturing, he said. '