New data could move Enhertu into early breast cancer

 AstraZeneca and Daiichi Sankyo's anti-HER2 drug Enhertu has been shown to provide a benefit in a phase 3 trial in early-stage breast cancer for the first time, setting up regulatory filings.

The DESTINY-Breast11 study is pitting Enhertu (trastuzumab deruxtecan) followed by paclitaxel, trastuzumab and pertuzumab (THP) against standard care – chemotherapy followed by THP as a pre-surgery (neoadjuvant) regimen – in patients with high-risk, locally advanced HER2-positive early-stage breast cancer.

Approximately one in three patients with early-stage breast cancer are considered high risk, as they are more likely to experience disease recurrence and have a poor prognosis.

So far, AZ and Daiichi Sankyo's drug has shown it is better at achieving a pathological complete response (pCR), no signs of cancer are found in the tissue removed during surgery, which is the main outcome measure. At the moment, nearly half of the patients in this population who receive neoadjuvant treatment do not achieve pCR.

The two companies are following patients to see if they also show a significant improvement in event-free survival (EFS) with Enhertu compared to standard care. At the moment, there is an "early positive trend" for their antibody-drug conjugate (ADC) for that endpoint.

Enhertu is already approved for more advanced cases of HER2-positive breast cancer, as well as a string of other oncology indications, and made $3.75 billion in sales last year whilst adding another $1.09 billion in the first three months of 2025.

The new data and other recent trial results, including the phase 3 DESTINY-Breast09 trial in previously-untreated, HER2-positive advanced breast cancer, suggest that there could be plenty more growth to come as AZ drives towards a target of raising its annual revenues from a 2024 level of just over $54 billion to more than $80 billion in 2030.

AZ's head of oncology R&D, Susan Galbraith, said that the data show that Enhertu has the potential to challenge the current treatment approach in early-stage breast cancer.

"Enhertu is already an important treatment option in the metastatic setting, and these data have the potential to allow this medicine to move into early stages of disease where cure is possible," she added.

AZ and Daiichi Sankyo recently claimed their first approvals for a second ADC, TROP2-directed Datroway (datopotamab deruxtecan) as a treatment for patients with metastatic HR-positive, HER2-negative breast cancer who have previously been treated with endocrine therapy and at least one line of chemotherapy.

AstraZeneca has a target of $5 billion or more in peak annual sales for both Enhertu and Datroway as it pitches at its 2030 revenue target.

https://pharmaphorum.com/news/new-data-could-move-enhertu-early-breast-cancer

Novo Cuts Outlook, Pledges Crackdown On Copycat Obesity Drugs

 Novo Nordisk shares surged as much as 6.5% in European trading, making it a top performer on the Stoxx 600, as Wall Street analysts said the Danish drugmaker's guidance cut was largely priced in—and pressures on Wegovy sales from compounded anti-obesity drugs may soon ease. 

Investor sentiment was also buoyed by expectations that Wegovy sales, will rebound in the second half, as the availability of compounded copycat versions declines.

"We have reduced our full-year outlook due to lower-than-planned branded GLP-1 penetration, which is impacted by the rapid expansion of compounding in the U.S. We are actively focused on preventing unlawful and unsafe compounding and on efforts to expand patient access to our GLP-1 treatments," Novo CEO Lars Fruergaard Jorgensen wrote in a statement. 

Jorgensen told CNBC in an interview earlier, "Compounders took a part of our business away," adding, "We now expect that compounding will be knocked off, so to say, and we get that business growth going forward."

For 2025, NOVO forecasted sales growth of 13% to 21% at constant exchange rates, below the February forecast of 16% to 24%. Operating profit growth is expected to be between 16% and 24%, compared with an earlier estimate of 19% to 27%. 

"The updated sales outlook reflects lower-than-planned penetration of branded GLP-1 treatments in the U.S., impacted by compounded GLP-1s. Novo Nordisk is focused on preventing unlawful compounding and further expanding access in the U.S.,"  Novo explained.  

Novo reported better-than-expected net profit results in the first quarter, coming in at 29.03 billion Danish kroner, ahead of the Bloomberg Consensus estimate of 27.91 Danish kroner. 

Sales of Wegovy rose 85% annually at constant exchange rates to 17.36 billion Danish kroner, missing the estimate of 18.98 billion Danish kroner. 

Some on Wall Street suggest the surge in compounded anti-obesity drug availabilities largely drove the guidance cut. Now, with those formulations beginning to exit the U.S. market as Wegovy-related shortages ease, analysts see a potential inflection point for Novo's sales in the second half. 

Wall Street commentary (courtesy of Bloomberg):

JPMorgan (overweight)

• The cut to guidance has already been priced into the shares, analyst Richard Vosser writes in a note
• Any share-price weakness today would be a buying opportunity "ahead of the potential for improving Wegovy growth as the compounders exit the US market"

UBS (buy)

• The guidance downgrade was "broadly expected by the market," analyst Jo Walton writes in a note
• UBS estimates for FY sales and Ebit growth are "well within the new range"

Intron Health (sell)

• Even though the outlook has been cut, Intron's estimates are "unlikely to change" given they were already below guidance, analyst Naresh Chouhan writes in a note
• The price for Ozempic in the U.S. only fell 5% in 1Q, "which helps explain the 3% beat versus consensus"
• Still, it's unclear whether "that price is better or that there was a one off"

Morgan Stanley (equal weight)

• The new forecast suggests "meaningful uplift of Wegovy volumes" in 2H, analyst Thibault Boutherin writes in a note
• Sees consensus FY Ebit expectations moving by -6% at the mid- point

BMO (market perform)

• The cut to guidance was likely expected by many investors, but could still pressure the shares, analyst Evan David Seigerman writes in a note 
• The obesity care miss and guidance cut overshadowed a relatively in-line topline performance, as well as a bottom line beat, in 1Q

Barclays (overweight)

• The impact of compounding will be in focus on the call, analyst Emily Field writes in a note
• Wegovy pricing and group profitability when it comes to recent telehealth and CVS announcements will also be in focus

Jefferies (underperform)

• The 2025 outlook cut is "slightly greater than expected," analyst Benjamin Jackson says in a note
• Sees scope for consensus expectations to be downgraded even further on FX

Signs that the compounded drug threat may be easing gave Novo shares a boost, sending them up as much as 6.5% in European trading. The stock is still down 55% from its peak of 1,000 Danish kroner last summer and now trades at 16 times expected earnings—down from 40 times a year ago.

Paging Goldman's James Quigley (a Novo super bull) ... Is it time to buy the dip? 

https://www.zerohedge.com/markets/novo-cuts-outlook-copycat-anti-obesity-drugs-hit-sales

Summit’s Campaign To Conquer Keytruda Nears First Global Phase III Data

 

Keytruda is set to lose exclusivity in 2028, meaning Summit may face competition from cheaper biosimilars. Meanwhile, other branded drugmakers are also seeking to improve on the blockbuster checkpoint inhibitor.

Summit Therapeutics’ attempt to dislodge Merck’s mega blockbuster Keytruda is nearing a key moment. Building on results that supported ivonescimab’s approval in China, Summit is closing in on the first of a series of readouts from global Phase III trials of the bispecific antibody that could shape the future of cancer treatment.

Akeso, Summit’s Chinese partner, sent interest in PD-1/L1xVEGF bispecifics into overdrive in September 2024 when ivonescimab was linked to a 49% reduction in the risk of disease progression or death when used as a first-line treatment in non-small cell lung cancer (NSCLC), compared to Keytruda. Beating Keytruda, a drug that generated sales of almost $30 billion last year, established ivonescimab as one of the hottest assets in biopharma R&D.

Within three months of Akeso sharing the data, BioNTech paid $800 million to buy its PD-L1xVEGF bispecific partner Biotheus and Merck handed LaNova Medicines $588 million to enter the race. The companies are eager to carve out opportunities in a market that Summit values at more than $90 billion.

Ivonescimab Nears the Summit

Ivonescimab is the frontrunner. In May 2024, Chinese authorities approved the bispecific for use in a subset of NSCLC patients who have progressed after tyrosine kinase inhibitor (TKI) therapy. Akeso secured a broader Chinese label, covering first-line NSCLC patients, last month.

The biotech published overall survival (OS) data alongside news of the label expansion, sparking a debate about the chances that ivonescimab will unseat Keytruda. Akeso linked the bispecific to a 22.3% reduction in the risk of death compared to Keytruda in an interim OS analysis. The difference fell short of statistical significance and analysts were split on the implications for the asset.

Summit’s share price fell in the wake of the OS update but the biotech has chances to reverse the dip. Results from a global Phase III trial that is testing ivonescimab in NSCLC patients who progressed on a TKI are due in mid-2025. The indication is the setting where ivonescimab first won approval in China. Johnson & Johnson won approval for Rybrevant in patients who progress on the TKI Tagrisso last year.

Jack West, vice president of clinical development at Summit, discussed the competition on an earnings call May 1. The Rybrevant regimen “has a combination of efficacy with toxicity liabilities that looks very different from what chemo and ivonescimab offers,” West said, adding that clinicians see “a great need for alternatives that have a very different and potentially less challenging toxicity profile.”

The upcoming Phase III data will provide a first look at whether Summit can replicate the results of Akeso’s Chinese trials. Analysts are looking to the readout for hints about the prospects of global first-line NSCLC trials that are comparing ivonescimab to Keytruda. One trial is enrolling patients with high PD-L1 expression. The other study is accepting participants with any level of PD-L1 expression.

Merck established Keytruda as the go-to drug in PD-L1-high NSCLC patients in 2016, claiming a decisive edge over Bristol Myers Squibb in the process. BMS included patients with lower PD-L1 levels in its Phase III Opdivo study and missed its primary endpoint. Merck subsequently showed Keytruda improved OS in squamous NSCLC of any level of PD-L1 expression.

BioSpace/Annalee Armstrong

The studies made Keytruda the drug to beat in key NSCLC settings targeted by Summit, but the biotech could face a fight for the market even if it beats Merck’s blockbuster in the clinic. Keytruda is set to lose exclusivity in 2028, meaning Summit may face competition from cheaper biosimilars, and other branded drugmakers are seeking to improve on the blockbuster checkpoint inhibitor.

BioNTech and Merck Give Chase

Summit’s competition includes other PD-1/L1xVEGF bispecifics. BioNTech started a Phase II/III trial of its PD-L1xVEGF bispecific BNT327 in first-line NSCLC in January. Truist Securities analysts said in a note to investors that the candidate has a longer half-life than ivonescimab. BioNTech CEO Ugur Sahin said on an earnings call in November 2024 that BNT327 might achieve better response rates and durability, too, because it hits PD-L1 rather than PD-1. However, Sahin added that it is too early to tell if BNT327 has an edge.

Merck is the big name in the pack of companies chasing Summit and BioNTech. LM-299, a candidate that Merck licensed from LaNova, entered the clinic in October 2024. Merck executives defended themselves on an earnings call last month against an analyst’s suggestion that they are “chasing the frontrunners” rather than trying to do something innovative.

Part of the defense rested on the potential for Merck to leapfrog the competition and take the lead if PD-1/L1xVEGF bispecifics are combined with other assets. Speaking before Akeso’s interim OS miss last month, Dean Li, president of Merck Research Laboratories, said the field was still waiting to see overall survival benefits better than achieved from drugs such as Keytruda and to confirm in global studies the efficacy seen in China-based trials.

“Should that PD-1xVEGF show that OS benefit, we have an advantage of having unique portfolio agents that have clear potential for combinability,” Li said. “We are looking at our own data and the data in the field as we make those decisions.”

Merck’s rivals are also planning combinations, with BioNTech looking to pair BNT327 with candidates in its pipeline and Summit teaming with Pfizer to access the pharma’s antibody-drug conjugates (ADCs). The companies could face competition from other mechanisms and modalities, including ADCs. Jefferies analysts said in a note that Akeso’s OS miss could be good news for Daiichi Sankyo’s AstraZeneca-partnered ADC Datroway.

“Datroway and ivonescimab work by completely different mechanisms but may wind up competing for the same pool of non-squamous [NSCLC] patients,” the analysts said. “We remain bullish on Daiichi Sankyo ahead of upcoming Datroway events.” Topline data from a trial of Datroway in first-line NSCLC patients are due in the second half of 2025.

Expanding Beyond NSCLC

The trials of PD-1/L1xVEGF bispecifics in NSCLC are part of a broader R&D push. Developers are racing to prove their bispecifics can beat standalone PD-1/L1 drugs in indications where checkpoint inhibitors are established as well as unlock markets where treatments such as Keytruda never won approval. Small cell lung cancer and triple-negative breast cancer are among the indications the companies are targeting.

Data from the trials will affect thousands of patients and shape markets worth tens of billions of dollars. The full story will take years to play out, but the mid-2025 readout on ivonescimab could go down as a key early chapter in the tale.

https://www.biospace.com/business/summits-campaign-to-conquer-keytruda-nears-first-global-phase-iii-data

Amid Trump’s Trade War, Some Drugmakers Stockpile Products in U.S

 

Imports of pharmaceutical products surged in March, most of which came from Ireland, historically one of the biggest exporters of medicines to the U.S.

President Donald Trump’s trade war appears to be disrupting the supply chain of pharmaceutical products, forcing some companies to bloat their reserves in the U.S. and pushing others to search for better business horizons elsewhere.

New data from the U.S. Department of Commerce released on Tuesday showed that imports of pharmaceuticals exceeded $50 billion in March alone, already equivalent to a fifth of all pharma imports last year. The U.S. took in nearly $108.2 billion worth of pharma imports during that period—nearly double that during the same period in 2024.

Ireland stood out in the Tuesday report. Imports of all goods from the European country spiked in March to $30.7 billion, more than doubling the $15.2 billion import figure in February. Of note, imports from Ireland topped China in March, with imports from the Asian giant slowing to roughly $29.4 billion that month.

The Commerce Department report does not disaggregate country-specific imports into their different end uses. However, Ireland has historically been among the biggest exporters of medicines to the U.S., suggesting that the import spike in March could be an effort by pharma companies to get ahead of Trump’s tariffs by beefing up their domestic product stockpiles.

Matthew Martin, senior U.S. economist at Oxford Economist, said that “while we had known consumer goods accounted for the bulk of March’s rise, we can now see pharmaceutical products were $20 billion higher—almost all of which were imported from Ireland,” as per a Tuesday report from Reuters.

Trump has for several weeks been threatening the pharma industry with tariffs, which he claims could encourage companies to move their manufacturing operations back to the U.S. Last month, the Commerce Department opened a national security probe on pharma imports, a process that produces a report to Trump, giving him the impetus to enact certain trade restrictions on the industry, including tariffs.

In response to these threats, several of the biggest pharma players have announced massive investments in the U.S., including Eli Lilly, Johnson & Johnson, Novartis and, most recently, Bristol Myers Squibb.

The current economics of drug manufacturing are reverberating in the European market as well. The Danish manufacturer Xellia Pharmaceuticals, which has been operating in the red, is closing shop in Copenhagen, Denmark and relocating its operations to China, according to a Tuesday report from the Financial Times.

“We are discussing so much about reshoring,” Xellia CEO Michael Kocher told FT. “I think it’s just as important to make sure that what we have in Europe stays in Europe.” Xellia, which produces active pharmaceutical ingredients for antibiotics, said that it is being outcompeted by Chinese companies. The only way for it to stay afloat, as per the FT report, is to move its facility to China.

Xellia is owned by Novo Holdings, the controlling shareholder of Novo Nordisk, and does business with more than 500 companies in 80 countries. The Copenhagen closure will result in 500 jobs lost.

https://www.biospace.com/business/amid-trumps-trade-war-some-drugmakers-stockpile-products-in-u-s

Long COVID may cause long-term changes in heart and lungs, leading to cardiac and pulmonary diseases

 Patients suffering from long COVID may exhibit persistent inflammation in the heart and lungs for up to a year following SARS-CoV-2 infection—even when standard medical tests return normal results—potentially placing them at elevated risk for future cardiac and pulmonary conditions. These findings come from a new study conducted by researchers at the Icahn School of Medicine at Mount Sinai and published April 30, in the Journal of Nuclear Medicine.

The study, the largest of its kind using advanced PET/MRI imaging, discovered significant abnormalities in cardiovascular and pulmonary tissues, as well as altered levels of circulating immune-regulating proteins, in long COVID patients. These abnormalities could serve as early warning signs of diseases such as heart failure, valvular heart disease, and pulmonary hypertension.

"Long COVID has emerged as a major public health challenge, and the long-term sequelae remain largely undefined," says corresponding author Maria G. Trivieri, MD, Ph.D., Associate Professor of Medicine (Cardiology), and Diagnostic, Molecular and Interventional Radiology at the Icahn School of Medicine.

"This study brings us closer to understanding how SARS-CoV-2 affects the heart and lungs over time. We believe long COVID results in an inflammatory response that may predispose patients to premature coronary artery disease, pulmonary hypertension, and valvular damage such as stenosis or regurgitation."

"Since 2020, we have been publishing work showing that even mild or asymptomatic COVID infections can have serious cardiovascular consequences, even in previously fit and healthy individuals," says David Putrino, Ph.D., the Nash Family Director of Mount Sinai's Cohen Center for Recovery from Complex Chronic Illness.

"This paper provides more data to highlight that SARS-CoV-2 is a virus that profoundly affects vascular health and that every new infection can do damage. Infection prevention is crucial."

Researchers studied 100 adult Mount Sinai patients who had a confirmed COVID-19 infection between December 2020 and July 2021 and were experiencing persistent cardiopulmonary symptoms. Most of these patients had no previous diagnosis of cardiovascular disease.

About 300 days after their initial infection, 91 participants underwent hybrid 18F-fluorodeoxyglucose positron emission tomography combined with magnetic resonance imaging (PET/MRI), an advanced imaging method that simultaneously detects structural and metabolic abnormalities.

Among those scanned, 52 patients—representing 57%—demonstrated evidence of inflammation affecting the heart muscle, pericardium (the thin sac that surrounds the heart), heart valves, particularly the mitral valve, and the aortic and pulmonary blood vessels. In several cases, more than one of these regions was affected.

The PET/MRI scans revealed myocardial (heart muscle) abnormalities in 22 participants, characterized by scarring and thickening of the tissue, similar to findings of myocarditis or cardiomyopathy. Pericardial involvement was seen in 20 patients, indicating either inflammation or effusion, a buildup of fluid. Inflammation near the mitral valve was identified in 10 participants, and vascular inflammation involving the aorta or pulmonary arteries was observed in 28 participants.

All abnormalities were associated with persistent symptoms such as chest pain, fatigue, and shortness of breath.

In parallel, researchers performed plasma protein analysis, which showed abnormal patterns in key biomarkers that regulate inflammation and immune signaling. These findings correlated with the imaging abnormalities, providing molecular-level confirmation of persistent inflammation.

To further validate the results, a control group of nine individuals with confirmed prior COVID-19 infection but no lingering cardiopulmonary symptoms was studied between March and October 2023. These controls underwent the same imaging and blood testing and did not exhibit the inflammatory changes observed in the symptomatic long COVID cohort.

"We found a range of cardiopulmonary inflammatory patterns, backed by abnormal protein profiles," Dr. Trivieri says. "These insights could have far-reaching implications for diagnosis and surveillance. If patients experience lingering symptoms such as shortness of breath, they should consult a physician for further evaluation.

"Our results should also raise awareness among clinicians to consider a patient's COVID history and evaluate persistent symptoms more thoroughly."

Zahi Fayad, Ph.D., senior author of the study and Director of the Biomedical Engineering and Imaging Institute at the Icahn School of Medicine at Mount Sinai, emphasized the broader impact of these findings. "This study highlights the unique power of hybrid PET/MRI imaging to uncover hidden disease processes in long COVID patients," Dr. Fayad says.

"These findings should change how we approach care and surveillance—not only recognizing SARS-CoV-2 as a potential long-term cardiovascular risk factor, but also integrating molecular imaging into post-COVID evaluation protocols. We now have objective evidence that can guide earlier detection and potentially prevent future cardiopulmonary events."

The Mount Sinai team continues to follow this patient cohort to assess long-term outcomes and is exploring whether these imaging and biomarker patterns can help predict who is most at risk for developing chronic cardiovascular or pulmonary disease after COVID-19.

More information: Maria Giovanna Trivieri et al, Prevalence of Persistent Cardiovascular and Pulmonary Abnormalities on PET/MRI and DECT Imaging in Long COVID Patients, Journal of Nuclear Medicine (2025). DOI: 10.2967/jnumed.124.268980

https://medicalxpress.com/news/2025-05-covid-term-heart-lungs-cardiac.html

COVID boosters might not be updated for next season, FDA commissioner says

 The head of the U.S. Food and Drug Administration (FDA) reiterated Tuesday that the agency is applying a more skeptical approach to this year's round of COVID-19 vaccine boosters.

Companies applying for approval of COVID boosters are being encouraged to use "gold standard science," including full-fledged clinical trials involving healthy people, FDA Commissioner Dr. Marty Makary said today at the American Hospital Association's annual meeting in Washington, D.C.

That approach could mean no COVID boosters will be approved in time for next winter's respiratory disease season, Makary has warned in earlier interviews.

"We need some better data. We can't just extrapolate from a clinical trial from four or five years ago," he said at the conference. "Americans have a very low uptake and a very low confidence of the COVID boosters right now."

For example, 85% of health care workers did not get the last COVID booster, Makary noted.

"It's reasonable to say we'd like to see a clinical trial rather than just some antibodies that spike after you give [the vaccine]," he said. "You can make antibodies spike to anything. That doesn't tell us that it actually has a clinical benefit. Americans want to know do we really, is there really a clinical benefit in healthy subjects."

The FDA also is considering whether COVID boosters should be given primarily to high-risk groups, as opposed to general coverage, Makary added.

"Should we really be putting the full weight of the government to urge vaccination against COVID for a healthy, thin 12-year-old girl with her seventh COVID booster right now today in America?" Makary said. "I don't think so."

The commissioner also downplayed the impact that layoffs ordered by the Trump Administration might have on the FDA's effectiveness.

"There's a lot of people with impressive sounding titles, but that may not necessarily mean that they are working towards the core mission of the agency, which is to deliver more cures, diagnostics, therapeutics and healthy foods," Makary said. "We're committed to public safety, which was why none of the cuts that were made included scientific reviewers or inspectors."

The FDA has doubled its staff since 2007, Makary said, increasing from 9,500 employees to 19,000 employees just a few months ago.

Under the Trump Administration, there's been a 12% reduction in the work force, Makary said, noting that's a lower level of staffing cuts than those ordered under President Bill Clinton for the U.S. Department of Health and Human Services.

"We need a lean FDA that's efficient, not a bloated FDA that is inefficient and slows down our approvals and inspections," Makary said.

More information: The U.S. Centers for Disease Control and Prevention has more on COVID-19 vaccines.

https://medicalxpress.com/news/2025-05-covid-boosters-season-fda-commissioner.html

Clover HealthUps Guidance on Earnings Turnaround: Revenue Up 33%, Medicare Members + 30%

Clover Health (NASDAQ: CLOV) reported strong Q1 2025 results with significant improvements across key metrics. The company's Medicare Advantage membership grew 30% year-over-year to 103,418 members, while total revenues increased 33% to $462 million. Profitability metrics showed remarkable improvement, with GAAP net loss narrowing to $1 million from $19 million year-over-year, and Adjusted EBITDA rising 279% to $26 million. The company's Clover Assistant technology demonstrated strong performance, with data showing 18% lower hospitalizations and 25% lower 30-day readmissions for Congestive Heart Failure patients. Based on these results, Clover Health improved its full-year 2025 guidance, projecting Medicare Advantage membership growth of 30% and insurance revenue between $1.8-1.875 billion, representing 37% growth year-over-year at the midpoint.

https://www.stocktitan.net/news/CLOV/clover-health-reports-first-quarter-2025-results-and-improves-full-g2vsks4khacp.html