The number of employees laid off dropped year over year during the first quarter. BioSpace recaps the five largest layoffs, which included BMS and Novartis cuts.

A Cleveland Clinic-led clinical trial of tolebrutinib, an investigational oral Bruton’s tyrosine kinase inhibitor (a group of drugs originally developed to treat lymphomas and related blood disorders) demonstrated a 31% delay in the onset of six-month confirmed disability progression (CDP) in patients with non-relapsing secondary progressive multiple sclerosis (SPMS).

This work is published in the New England Journal of Medicine in the paper, “Tolebrutinib in Non-Relapsing Secondary Progressive Multiple Sclerosis.”

The first peer-reviewed results of the Phase III HERCULES trial (NCT04411641) were also presented during a clinical trials plenary session at the American Academy of Neurology 2025 Annual Meeting in San Diego. The data suggest that tolebrutinib is an effective treatment for non-relapsing SPMS, a form of the disease for which there are currently no FDA-approved treatments.

Tolebrutinib is an oral, brain-penetrant Bruton’s tyrosine kinase inhibitor that targets myeloid cells (including microglia) and B cells in both the periphery and central nervous system.

“This is the first clinical trial showing a positive effect in delaying disability progression in non-relapsing SPMS, a later form of the disease where neurological function gradually worsens over time and disability increases relentlessly,” said Robert Fox, MD, chair of the HERCULES Global Steering Committee and a neurologist at the Mellen Center for MS Research and Treatment at Cleveland Clinic.

“The findings demonstrate the drug’s impact on chronic neuroinflammation in the central nervous system, a key driver of this gradual disability observed in SPMS,” said Fox. “The drug offers the potential for a new class of medications for the treatment of MS, the leading cause of non-traumatic disability in young adults.”

While topline results of HERCULES (sponsored by Sanofi, the developer of tolebrutinib) were first presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting last September, the peer-reviewed paper offers new insights into the drug’s efficacy and safety profile.

Between Oct. 23, 2020, and Jan. 12, 2023, the randomized, double-blind, placebo-controlled trial enrolled 1,131 patients ages 18–60 at 264 sites across 31 countries. Patients with documented disability progression in the 12 months prior to screening and who had no clinical relapses in the 24 months before screening were randomly assigned at a 2:1 ratio to receive 60 mg oral tolebrutinib or a matching placebo tablet.

For the primary endpoint, the cumulative incidence of six-month confirmed disability progression was 22.6% in the tolebrutinib group versus 30.7% in the placebo group, which was a 31% reduction with tolebrutinib compared to placebo.

In addition, the drug demonstrated a positive effect across several of its secondary endpoints in disability progression and MRI-related measures:

• A similar degree of risk reduction was observed in the time to three-month confirmed disability progression.
•  A higher proportion of patients achieved improvement in disability with therapy, with a six-month confirmed disability improvement rate of 8.6% versus 4.5% with placebo.
• Measures of three-month sustained 20% increase in the timed 25-foot walk test favored tolebrutinib, but three-month sustained 20% increase in the nine-hold peg test was not impacted by tolebrutinib. In clinical trials of MS, these are standard tests used to measure walking ability and upper limb dexterity, respectively.
• The mean annualized rate of new and/or enlarging T2-weighted lesions, a test used to measure disease activity, including inflammation and tissue damage, was reduced with tolebrutinib compared with placebo.

 

Adverse event rates were broadly comparable between the tolebrutinib and placebo groups, although serious adverse events were more frequent with tolebrutinib. More specifically, “serious adverse events occurred in 15.0% of the participants in the tolebrutinib group and in 10.4% of those in the placebo group. A total of 4.0% of the participants in the tolebrutinib group and 1.6% of those in the placebo group had increases in alanine aminotransferase (ALT) levels to more than three times the upper limit of the normal range.” ALT is an enzyme reflecting liver injury. Although one patient treated with tolebrutinib died of complications related to liver failure, all cases of severe ALT elevation occurred within 90 days of treatment initiation.

Tolebrutinib is currently under review by the FDA. “If approved, the drug will likely require intensive monitoring of liver function enzymes during the first three months of therapy, with less frequent monitoring thereafter,” said Fox. “It appears that about one in 200 patients will have severe elevation of liver enzymes during the first three months of use, so careful monitoring is important, and the drug should be stopped immediately in those with liver enzyme elevations.”

Cancer diagnoses traditionally require invasive or labor-intensive procedures such as tissue biopsies. Researchers at the Ludwig-Maximilians-Universität München (LMU) have now reported on a method that uses pulsed infrared light to identify molecular profiles in blood plasma that could indicate the presence of some common cancers. In a proof-of-concept study, the team used machine learning to analyze blood plasma from more than 2,000 participants and link molecular patterns to lung cancer, extrapolating a potential “cancer fingerprint.”

Mihaela Žigman, PhD, at the Max Planck Institute of Quantum Optics (MPQ) is corresponding author of the team’s published paper in ACS Central Science, titled “Electric-Field Molecular Fingerprinting to Probe Cancer.” In their report, the team concluded, “Our study demonstrates that electric-field molecular fingerprinting is a robust technological framework broadly applicable to disease phenotyping under real-world conditions.”

Various physiological states, and some diseases, may be reflected in the molecular makeup of biofluids such as blood and plasma, which is the liquid portion of blood depleted of any cells, the authors explained. Plasma carries diverse molecules such as proteins, metabolites, lipids, and salts throughout the body and some molecules carried by blood plasma indicate potential health conditions. For example, unusually high levels of prostate-specific antigen are used to screen for prostate cancer. Theoretically, a medical test that measures a broad range of molecules could identify a pattern specific to different cancers, leading to quicker diagnoses and reduced costs.

The use of sensitive and specific analytical methods in the fields of proteomics and metabolomics has led to the discovery of various molecular “biomarker candidates” the authors noted. “However, current omics techniques are often still limited in the range of molecular species that they can probe at once. They often require complex, target-specific preanalytical workflows for sample preparation.”

A technique known as molecular fingerprinting, “… where phenotype detection is based on patterns of change across the entire molecular landscape,” could represent an alternative approach, the researchers continued. “If a specific pattern shows a robust correlation with a particular physiological state, it may contribute to the detection of a phenotype.”

For their newly reported study, Žigman and colleagues tested a technique called electric-field molecular fingerprinting (EMF), which uses pulsed infrared light, to profile complex molecular mixtures in blood plasma and look for telltale chemical patterns of cancer.

First, the researchers used the electric-field molecular fingerprinting technique to send ultra-short bursts of infrared light through plasma. They analyzed samples from 2,533 study participants, including people with lung, prostate, breast, or bladder cancer and those without cancer. For each sample, they recorded the pattern of light emitted by the molecular mixtures in the plasma, the “infrared molecular fingerprint.” Using these complex patterns from individuals with and without cancer, the researchers taught a machine learning model to identify molecular signatures associated with the four types of cancer.

The computer model was tested on a separate subset of participants’ samples to see how well the model could perform on unseen test data. The analytical technique demonstrated a convincing level of accuracy (up to 81%) in detecting lung cancer-specific infrared signatures and differentiating them from control samples obtained from individuals without cancer. “In an independent held-out test data set, designed to reflect different experimental conditions from those used during model training, we achieved a lung cancer detection ROC AUC of 0.81… This independent testing allows us to assess the generalizability of our technique beyond a single measurement campaign, revealing that our lung cancer detection model remains robust under realistic measurement shifts, maintaining its diagnostic performance and demonstrating its potential reliability,” they noted.

The computer model’s performance did demonstrate lower success rates in detecting the other three cancers. The observed discrepancies, particularly in the capacity to detect the other three cancer entities, the authors noted, “… highlight the need for improving the reproducibility of EMF measurements and for further validation of this approach in additional patient populations.”

Nevertheless, they wrote, “Our findings indicate that patterns in infrared fingerprints can reliably be associated with physiological states … In conclusion, the current findings provide compelling evidence underscoring the potential of electric-field molecular fingerprinting for minimally invasive disease detection.”

In the future, the team aims to expand and test the approach to identify additional cancer types and other health conditions. “Future enhancements, such as broader spectral coverage, increased detection sensitivity and specificity, multidimensional measurements, and interferometric subtraction, could further boost biomedical potential,” they stated. “Expanding clinical studies to larger cohorts, focusing on early disease states and independent clinical testing, and exploring various disease phenotypes and their combinations will be crucial for developing a reliable diagnostic platform to improve cancer outcomes.”

Žigman added, “Laser-based infrared molecular fingerprinting detects cancer, demonstrating its potential for clinical diagnostics. With further technological developments and independent validation in sufficiently powered clinical studies, it could establish generalizable applications and translate into clinical practice—advancing the way we diagnose and screen for cancer today.”

GSK is paying to access ABL Bio’s Grabody-B platform, which potentially enables therapies to cross the blood-brain barrier.
GSK is fronting £38.5 million (nearly $50 million), in a partnership with South Korea’s ABL Bio to develop novel drugs for neurodegenerative diseases.

Aside from its upfront payment, GSK will also be on the hook for up to £2.075 billion ($2.66 billion) in research, development, regulatory and commercialization milestones, spread across the deal’s several potential programs. All told, the deal could mean more than a $2.5 billion windfall for ABL Bio.

At the center of Monday’s agreement is the South Korean biotech’s proprietary Grabody-B platform, which makes use of a novel targeting mechanism that allows bulkier therapeutic molecules to pass the blood-brain barrier.

According to the biotech’s website, ABL Bio’s approach leverages a bispecific antibody engineered to bind to the insulin-like growth factor 1 receptors, which are found on the cells that make up the blood-brain barrier, and in which turn allows the molecule to be shuttled across the barrier.

As per Monday’s deal, ABL Bio will transfer Grabody-B-related technologies and expertise to GSK. GSK will then be responsible for preclinical and clinical development, as well as taking charge of manufacturing and commercialization activities. ABL Bio will be entitled to tiered royalties on net sales of any product that results from this partnership.

GSK has not disclosed specific target indications, though Christopher Austin, senior vice president of Research Technologies, said in a prepared statement on Monday that the ABL Bio partnership is part of the pharma’s push to address “neurodegenerative brain diseases,” particularly those that are becoming more common “due to the aging of the population.”

GSK has pushed deeper into the neuro space in recent months. In December 2024, it paid $35 million upfront to partner with Danish biotech Muna Therapeutics to get access to its MiND-MAP platform.

GSK will be able to work on “multiple, high-value, validated” Alzheimer’s disease targets under the Muna partnership, though it hasn’t yet disclosed a specific number. For each target, Muna will be entitled to up to roughly $148 million in milestones.

In November 2024, GSK also partnered with Vesalius Therapeutics to leverage its proprietary platform, which according to Vesalius combines genomics, stem cells and AI, and use that platform to develop novel therapies for Parkinsons’s disease and another neurodegenerative disease. The pharma paid $80 million upfront and also pledged up to $570 in milestones for one preclinical program. Vesalius will also be entitled to undisclosed milestones and tiered royalties for each novel target.

Bio-Rad Laboratories, Inc.’s BIO Clinical Diagnostics business is back to its usual growth trajectory post-pandemic while maintaining a strong market position worldwide for key platforms. The company’s QX600 Droplet Digital PCR (ddPCR) platform is currently robust and continues to grow. It also conducts significant international operations, having direct distribution channels in more than 36 countries outside the United States. Yet, ongoing challenges in the biopharma end-market and currency headwinds remain concerns.

In the past year, shares of this Zacks Rank #3 (Hold) company have fallen 24% against the industry’s 11% growth. The S&P 500 composite has seen a 9.9% rise in the same time frame.

The renowned manufacturer and global supplier of clinical diagnostics and life science research products has a market capitalization of $6.72 billion. Bio-Rad’s earnings surpassed estimates in three of the trailing four quarters and missed in one, the average surprise being 28.7%.

Let’s delve deeper.

Tailwinds for Bio-Rad

Clinical Diagnostics Continues to Gain Momentum: The business has now returned to its normalized growth rate post-pandemic, maintaining strong market positions globally for its platforms. Built on its long-standing reputation as a leading blood screening systems provider, Bio-Rad’s IH-500 blood typing system is considered a gold standard in immunohematology labs, offering the highest level of automation. The company introduced the IH-500 NEXT System in 2023, a fully automated system for ID cards to meet emerging demands and challenges in laboratory and health environments.

In 2024, the Clinical Diagnostics Group contributed $1.54 billion in sales, a 3.3% increase on a reported basis, primarily led by increased demand for quality control and blood typing products. On a geographic basis, currency-neutral year-over-year revenues in the diagnostics group reflected growth across all three regions.

Digital PCR Business Backs Bio-Rad’s Growth: Bio-Rad’s QX600 ddPCR platform is currently robust and continues to expand. In the fourth quarter of 2024, the Droplet Digital PCR franchise grew by mid-single digits and was bolstered by additional IP-related royalties. Moreover, several advancements were made to further expand the ddPCR platform into life science research and clinical diagnostics, such as investing in Geneoscopy to support the launch of their FDA-approved, non-invasive colorectal cancer screening test powered by the ddPCR platform.

Organon acquired regulatory and commercial rights in the United States for TOFIDENCE™, a biosimilar to ACTEMRA®, for intravenous infusion from Biogen. TOFIDENCE, the first approved tocilizumab biosimilar entrant in the U.S. market, was launched in May 2024 and is indicated in certain patients for the treatment of moderately to severely active rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and COVID-19.

“Biosimilars continue to be a key growth driver for Organon, and this acquisition complements our existing business, enabling us to expand our immunology portfolio,” said Kevin Ali, Organon’s CEO. “We believe that by leveraging our commercial expertise and market access capabilities, there is considerable growth potential for this product.”

The agreement includes an upfront payment to Biogen, with Organon assuming the obligation to pay tiered royalty payments based on net sales and tiered annual net sales milestone payments owed by Biogen to Bio-Thera Solutions.

Large growth market

The biosimilars market is forecasted to grow from $29.4 billion in 2023 to $66.9 billion by 2028, driven by a CAGR of 17.8%, according to a report by MarketsandMarkets. The market, focusing on drug classes such as monoclonal antibodies, insulin, erythropoietin (EPO), and anticoagulants, is poised for substantial growth driven by increasing demand for cost-effective treatments amid rising chronic disease rates and the patent expirations of major biologics, noted the report. A key trend cited includes the rapid approval and adoption of biosimilars, particularly in oncology.

Challenges include complex manufacturing processes and regulatory obstacles, which are countered by opportunities in less regulated markets like Asia Pacific, noted the report, which cites players such as Novartis, Pfizer, and Amgen as pivotal in shaping industry dynamics through innovation and strategic expansions.

Ethris and Lonza agreed to collaborate on the development of room-temperature stable, spray-dried formulations of mRNA-based vaccine candidates, designed for mucosal delivery to combat respiratory diseases.

Room-temperature stability aims to address significant supply chain challenges associated with some mRNA vaccines, including the dependence on ultra-low-temperature storage and complex delivery systems, according to Carsten Rudolph, PhD, CEO, Ethris. Overcoming these challenges will simplify production, reduce costs, and support rapid, scalable vaccine development, he added, noting that spray-dried formulations of mRNA-based vaccine candidates aim to enable needle-free nasal administration, potentially achieving mucosal immunity.

“Together, I believe we are well positioned to create promising noninvasive mucosal vaccine candidates that could potentially transform how respiratory diseases are prevented globally,” Rudolph said.

The initial focus of the collaboration is to develop a first-in-class mRNA vaccine candidate against influenza delivered nasally. This noninvasive approach is designed to provide localized immune responses with an immune effect comparable to intramuscular vaccines and could reduce virus transmission by generating mucosal immunity at the site of virus entry.

Lonza will provide spray-drying and particle engineering for vaccine candidates based on Ethris’ stabilized non-immunogenic mRNA (SNIM® RNA) and stabilized lipid nanoparticles (SNaP LNP) platform at its Bend, OR, site, which specializes in addressing bioavailability challenges and modulating pharmacokinetics to meet target product profiles.

“Spray-drying represents a well-established technique that addresses solubility and other manufacturing and stability challenges,” pointed out Jan Vertommen, head of commercial development, advanced synthesis. “However, its application in the field of DNA and RNA-based products represents a highly innovative approach, with another level of complexity introduced by the presence of LNPs.”

President Donald Trump’s exemption of pharmaceuticals from the “reciprocal” tariffs he announced Wednesday limited the declines of biopharma stocks as financial markets tanked late last week—but the specter of future industry-specific tariffs and import duties still hanging over the industry means that shares of biotech and pharma drug developers are hardly out of the proverbial woods.

Biopharma stocks mostly showed declines this past week, buffeted first by the sudden departure of Peter Marks, MD, as director of the FDA’s Center for Biologics Evaluation and Research (CBER), which pushed shares mostly downward on March 31—especially developers of cell therapies, gene therapies, other biologics, and vaccines, all overseen by CBER. The following day, the U.S. Department of Health and Human Services (HHS) began a staggering shrinkage of its workforce, eliminating some 10,000 jobs at the FDA, NIH, and U.S. Centers for Disease Control and Prevention (CDC).

A day later, Trump effectively ended the age of “free trade” by announcing a 10% minimum baseline tariff rate on all imports from all countries effective Saturday—plus reciprocal tariffs set at individual rates for more than 180 countries and territories with which the United States has run the largest trade deficits, including China (34% added to 20% tariff imposed in February), and the European Union (20%). The reciprocal tariffs take effect on April 9.

According to investment research and management firm Morningstar, last year the United States exported $95 billion in pharmaceutical products—but imported more than double that amount, about $200 billion.

“With roughly $200 billion in pharmaceutical imports in 2024, a 10% tariff could amount to a $20 billion headwind across the industry, with the biggest firms seeing potential annual tariffs as high as $1 billion,” predicted Karen Andersen, equity director with Morningstar, in a research note Thursday.

Figuring out which biopharmas face the greatest impact from future tariffs is a challenge, she added.

“While we have some information on which major products are manufactured in which countries, they are often produced in multiple geographies, making it difficult to determine the exact percentages being produced in the United States and whether finishing might be done in another country,” Anderson wrote.

While a future global pharmaceutical tariff could potentially lower gross margins while raising long-term tax rates, Andersen added: “We expect firms to be able to adapt their manufacturing, and nearly all large-cap biopharma firms continue to hold wide economic moats.”

Manufacturing plans “could help offset” tariff risks

Richard de Chazal, macroeconomic analyst with William Blair, noted in a report Thursday that several biopharma giants have announced plans for new U.S. manufacturing facilities over the past 12 months—including Amgen ($1 billion second drug substance manufacturing plant in Holly Springs, NC); Eli Lilly (four sites totaling $27 billion); Novo Nordisk ($4.1 billion second fill and finishing facility in Clayton, NC); and Johnson & Johnson (four plants totaling $55 billion-plus). Those plans, according to de Chazal, signal “a continued goal of globalized infrastructure that could help offset longer-term tariff risks.”

However, de Chazal cautioned that an earlier Trump threat of biopharma tariffs potentially 25% or higher “suggests the industry’s relief will be short-lived.

“If—or perhaps more appropriately, when—pharma-specific tariffs are rolled out, there will not be a material direct impact on most pharmaceutical outsourcing and services companies,” de Chazal observed. “That said, since tariffs would pressure margins for commercial drugs and likely make developing drugs more expensive, the taxes could potentially discourage investments in research and development, which in turn would lead to a more challenging demand environment for our coverage list.”

He said the brunt of any future tariff impacts on biopharma would likely be felt by pharma giants—“but it would also add to a large pile of unsettling news creating uncertainty around biotech funding and ultimately demand from smaller innovators.”

Among contract research organizations (CROs) and providers of tech-enabled services, de Chazal added, Charles River Laboratories (NYSE: CRL) would have the most direct exposure to tariff impacts, since about 18% of revenue is tied to non-pharmaceutical product sales, while Lonza Group (SIX Swiss Exchange: LONN) would also be negatively impacted by a slowdown in R&D spending, but to a lesser extent than other companies tracked by William Blair, since Lonza generates 70% of its contract development and manufacturing organization (CDMO) revenue from Phase III and commercial drugs. Lonza also has some potential direct exposure to tariffs through its capsules and health ingredients (CHI) segment, which accounted for 16% of 2024 revenue, the analyst noted.

“On the bright side, we believe Lonza is extremely well positioned to benefit from increased demand for U.S. manufacturing capacity” given its its $1.2 billion acquisition of Genentech’s large-scale biologics manufacturing site in Vacaville, CA, from parent company Roche last year, de Chazal added.

“Liberation” and engagement

During his “Liberation Day” ceremony Wednesday announcing the baseline and reciprocal tariffs, Trump didn’t mention his administration’s earlier threat of industry-specific tariffs. But he lamented what he called a dearth of U.S. drug making and predicted increased domestic manufacturing activity for biopharma would result from his policies.

“The United States can no longer produce enough antibiotics to treat our sick,” Trump said, adding: “We’re going to produce the cars, ships, chips, airplanes, minerals, and medicines that we need right here in America.”

“The pharmaceutical companies are going to come roaring back. They are coming roaring back. They are all coming back to our country because if they don’t, they got a big tax to pay. And if they do, I’ll be very happy,” Trump added.

Trump’s administration has specified the composition of pharmaceuticals exempted from the reciprocal tariffs in an annex to the executive order under which they were enacted. The exemption appeared to represent early success for biopharma leaders following weeks of engagement with Trump and his administration aimed at staving off tariffs and promoting other industry-friendly policies:

• Pfizer Chairman and CEO Albert Bourla, DVM, PhD—who is also chair of industry group Pharmaceutical Research and Manufacturers of America (PhRMA)—said last month his company could carry out additional drug production in the United States, where it operates 13 manufacturing sites, in order to get around tariffs.

• Bourla and PhRMA president and CEO Stephen J. Ubl led a February 20 meeting of industry leaders with Trump

• David A. Ricks, Lilly chair and CEO, and Amgen chairman and CEO Robert A. Bradway in recent weeks have both publicly credited Trump’s 2017 tax cuts with enticing them to build their manufacturing sites in the United States

“He delivered the tax reform and we delivered the investment in creating high-paying attractive science-based jobs as a result,” Bradway said at the groundbreaking for Amgen’s Holly Springs manufacturing expansion.

Biopharma funds slide with Wall Street

The tariff announcements sparked headline-grabbing stock selloffs in financial markets worldwide that led to low- to mid-single-digit declines Thursday of 2.8% (Japan’s benchmark Nikkei 225 index), 4% (Dow Jones Industrial Average), 4.8% (S&P 500), and 5.97% (Nasdaq Composite). The U.S. markets finished with their worst one-day declines since March 16, 2020, days into the COVID-19 pandemic. The Wall Street slide continued into Friday with declines of 2.75%, 4.96%, 5.5%, and 5.48%, respectively.

However, five of the top six biotech electronic transfer funds (ETFs) as ranked by VettaFi finished last week with double-digit losses between March 28 and Friday. The largest ETF, iShares Biotechnology ETF (NASDAQ: IBB) fell 10.1% from $130.29 to $117.16, compared with a 12.8% loss for the second largest ETF, SPDR S&P Biotech ETF (NYSE Arca: XBI), from $84.40 to $73.63.

The third-largest biotech ETF, First Trust NYSE Arca Biotechnology Index Fund (NYSE Arca: FBT) slid 10.2%, from $170.12 to $152.75, while the fourth-largest, ARK Genomic Revolution ETF (CBOE: ARKG) slipped 11.8% from $21.55 to $19.

Two notable exceptions arose at both ends of the price spectrum. Falling worse than the top four ETFs was the number five ETF, Direxion Daily S&P Biotech Bull 3X Shares (NYSE Arca: LABU), which nosedived nearly 36%, from $69.07 to $44.45. Faring best among the top six ETFs was VanEck Pharmaceutical ETF (NASDAQ: PPH), the sixth largest biopharma ETF, which consists of the shares of 25 pharma giants. PPH shares dropped about 7.5% from $90.65 to $83.89.

“We await potential future pharma sector tariffs in the next month or so and subsequent developments,” Risinger added.

He said those future tariffs will show significant impacts on biopharma manufacturers including 21 companies spotlighted by Leerink in a March 30 report.

Biopharma stock declines could intensify, some analysts warned, if Trump follows through on his earlier talk about levying biopharma tariffs, and especially if his administration imposes import duties—an additional possibility that emerged from news reports that the U.S. Department of Commerce may launch an investigation under Section 232 of the Trade Expansion Act of 1962 into whether drug imports by multinational biopharmas threaten national security.

“President Trump could announce pharma sector tariffs, possibly in the next month or so. When potential sectoral tariffs are announced, we’ll have to see if there are specific company exemptions (potentially those committing to significant investments in the United States),” David Risinger, a senior managing director and senior research analyst covering diversified biopharmaceuticals with Leerink Partners, cautioned in a research note.

Reciprocal risks as China, EU respond

“Additionally, if pharma sector tariffs are announced, we see risks from reciprocal actions by ex-U.S. countries.”

China responded Friday, as its Customs Tariff Commission of the State Council imposed an additional 34% tariff on all U.S.-origin goods effective April 10, and the country’s Ministry of Commerce filed a lawsuit with the World Trade Organization (WTO) challenging the reciprocal tariffs.

“China urges the United States to immediately remove unilateral tariffs and resolve differences with trade partners through dialogue,” a Ministry of Commerce spokesperson said in remarks reported by Global Times, an English-language newspaper published by People’s Daily, the official newspaper of the Chinese Communist Party. “China firmly opposes this and will resolutely take countermeasures to safeguard its own rights and interests.”

“There is no winner in a trade war, and protectionism leads nowhere,” the spokesperson added.

Ursula von der Leyen, president of the European Commission, which oversees the European Union, said the EU will take countermeasures against U.S. tariffs in coming days should talks with Trump administration officials fail. The EU is drafting a set of tariffs on up to €26 billion ($28.4 billion) of U.S. goods set to take effect later this month, after Washington enacted tariffs on steel and aluminum on March 12.

“President Trump’s announcement of universal tariffs on the whole world, including the European Union, is a major blow to the world economy,” von der Leyen stated. “The global economy will massively suffer. Uncertainty will spiral and trigger the rise of further protectionism.”

EU member Ireland, where numerous U.S. biopharmas have manufacturing operations, says it continues to engage with the Trump administration under the working assumption that Washington will levy pharma-specific tariffs in the future.

Pharmaceutical exports account for 79% or about €58 billion (nearly $64 billion) of the €72.6 billion ($79.6 billion) in products that Ireland exported to the United States last year. IDA Ireland, the republic’s foreign investment attraction agency, said the Emerald Isle is home to more than 90 pharmaceutical companies that employ 45,000 people. Of those, around 30,0000 work for U.S.-based companies, according to the industry group Irish Pharmaceutical Healthcare Association (IPHA).

“We’re making the point that actually about 80% of what we produce in companies here that goes into the United States, from a pharma point of view, aren’t finished products,” Ireland’s Deputy Prime Minister or Tánaiste Simon Harris, the country’s Minister for Foreign Affairs and Trade, told Irish broadcaster RTE. “They’re commodities that actually go back into U.S. factories, create jobs for people to pay taxes there.”

Leaders and laggards

• Aldreya Therapeutics (ALDX) shares cratered 73% from $5.33 to $1.42 Thursday after the company announced that the FDA sent the company a complete response letter in response to its second submission of the New Drug Application (NDA) of reproxalap, a candidate designed to treat dry eye disease. The FDA contended that the NDA “failed to demonstrate efficacy in adequate and well-controlled studies in treating ocular symptoms associated with dry eyes” and that “at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye” should be conducted. The letter also cited methodological issues with trial data, including a difference in baseline scores across treatment arms. “Pending positive results from the ongoing clinical trials and discussions with the FDA, we look forward to a potential NDA resubmission mid-year 2025,” stated Todd C. Brady, MD, PhD, Aldreya’s president and CEO. The FDA rejected Aldreya’s first NDA for reproxalap in 2023.
• Allakos (ALLK) shares surged 45% from 22 cents to 32 cents Wednesday, after the company said it had entered into a definitive merger agreement with Concentra Biosciences, which agreed to acquire Allakos for 33 cents a share cash. Allakos’ board has approved the deal, which is subject to the tender of Allakos common stock representing at least a majority of the total number of outstanding shares, the availability of at least $35.5 million of cash (net of transaction costs, wind-down costs, and other liabilities) at closing, and other customary closing conditions. Allakos had been considering strategic alternatives since January.

Antibiotic resistance tends to stabilize over time, according to Sonja Lehtinen, PhD, from the University of Lausanne and colleagues. The team published its study, “The evolution of antibiotic resistance in Europe, 1998–2019,” in PLOS Pathogens.

Antibiotic resistance is a major public health concern, contributing to an estimated five million deaths per year, point out the scientists. Understanding long-term resistance patterns could help public health researchers to monitor and characterize drug resistance as well as inform the impact of interventions on resistance.

In this study, researchers analyzed drug resistance in more than three million bacterial samples collected across 30 countries in Europe from 1998 to 2019. Samples encompassed eight bacteria species important to public health, including Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae.

They found that while antibiotic resistance initially rises in response to antibiotic use, it does not rise indefinitely. Instead, resistance rates reached an equilibrium over the 20-year period in most species. Antibiotic use contributed to how quickly resistance levels stabilized as well as variability in resistance rates across different countries. But the association between changes in drug resistance and antibiotic use was weak, suggesting that additional, yet unknown, factors are at play.

“The evolutionary dynamics of antibiotic resistance are not well understood, particularly the long-term trajectories of resistance frequencies and their dependence on antibiotic consumption. Here, we systematically analyze resistance trajectories for 887 bug-drug-country combinations in Europe across 1998–2019, for eight bacterial species with a considerable resistance-associated public health burden,” wrote the investigators.

Analytical support for model

“Our analyses support a model in which, after an initial increase, resistance frequencies reach a stable intermediate equilibrium. The plurality (37%) of analyzed trajectories were best described as ‘stable’ (neither increasing nor decreasing). 21% of trajectories were best described as ‘stabilizing,’ i.e., showing a transition from increasing frequency to a stable plateau; 21% as decreasing and 20% as increasing.

“The antibiotic consumption in a country predicts both the equilibrium frequency of the corresponding resistance and the speed at which this equilibrium is reached. Moreover, we find weak evidence that temporal fluctuations in resistance frequency are driven by temporal fluctuations in hospital antibiotic consumption. A large fraction of the variability in the speed of increase and the equilibrium level of resistance remains unexplained by antibiotic use, suggesting other factors may also drive resistance dynamics.”

The study highlights that continued increase in antibiotic resistance is not inevitable and provides new insights to help researchers monitor drug resistance.

“When we looked into the dynamics of antibiotic resistance in many important bacterial pathogens all over Europe and in the last few decades, we often found that resistance frequency initially increases and then stabilizes to an intermediate level,” said Francois Blanquart, PhD, senior author and a researcher at the French National Center for Scientific Research (CNRS). “The consumption of the antibiotic in the country explained both the speed of initial increase and the level of stabilization.”

“In this study, we were interested in whether antibiotic resistance frequencies in Europe were systematically increasing over the long-term,” added Sonja Lehtinen, PhD, senior author and an assistant professor at the computational biology department at the University of Lausanne. “Instead, we find a pattern where, after an initial increase, resistance frequencies tend to reach a stable plateau.”

Syngenta Biotechnology China-led research, with partners in the U.S., France, the UK, Chile, the Netherlands, Argentina, and across China, has discovered that sunflowers can form viable haploid seeds through parthenogenesis in the absence of pollination. This discovery opens the possibility of a scalable doubled haploid system in sunflowers, a technique that could reduce the time needed to produce fully inbred lines from six years to ~10 months.

Some animals, including certain birds, reptiles, fish, and crustaceans like Daphnia, can reproduce without fertilization through a process known as facultative parthenogenesis. In these species, females can produce offspring without male involvement. Charles Darwin first documented unusual reproductive patterns in plants, but many aspects of plant reproduction remain poorly understood.

In most flowering plants, seed formation depends on a process called double fertilization. This involves one sperm fertilizing the egg and another fertilizing a separate cell that forms the endosperm, a tissue that nourishes the embryo. Without fertilization, viable seeds rarely develop.

Sunflower is one of the world’s most important oilseed crops, producing nearly 55 million metric tons globally in 2023. Because sunflower is a hybrid crop, improving its traits requires creating inbred parent lines, which typically takes six years through repeated self-pollination.

In the study, “Haploid facultative parthenogenesis in sunflower sexual reproduction,” published in Nature, researchers examined how sunflowers can form haploid seeds without fertilization. The team conducted a combination of genetic, chemical, and environmental experiments to identify the factors that enable parthenogenesis and support a scalable doubled haploid breeding system.

Researchers tested sunflower plants under controlled greenhouse, growth chamber, and field conditions to identify genetic backgrounds capable of producing haploid seeds without fertilization.

Experiments included chemical treatments, manual and hormonal suppression of pollen, and variation in environmental factors such as light intensity and temperature. Flow cytometry and genetic analysis confirmed haploid seed formation. Tissue culture and chromosome doubling techniques were applied to regenerate fertile, doubled haploid plants.

Formation of haploid seeds was first noticed during experiments using a chemical phospholipase inhibitor on pollen. Researchers observed small, shriveled seeds and initially attributed them to the chemical’s effects. Later trials showed the same seeds forming even in the complete absence of pollen, leading to the discovery of spontaneous parthenogenesis.

Genetic analysis confirmed the seeds were maternally derived and lacked paternal DNA. Parthenogenesis occurred across multiple sunflower lines, with some producing over 100 haploid seeds per flower head. High-intensity light significantly increased haploid yield, while blue or red light alone had no effect.

Maize pollen combined with boron improved haploid formation in certain genetic backgrounds. Germination trials showed a 40% success rate in soil.

Imaging showed that many haploid embryos which formed without fertilization had irregular shapes or multiple axis-like centers. Each seed still contained a single embryo, but some developed multiple shoot-like structures after germination. Tissue culture was used in regenerating healthy seedlings from these atypical forms.

Chromosome doubling produced fertile, seed-setting plants, with some individuals generating up to 188 seeds.

Unlike most flowering plants, sunflower embryos survived and germinated using nutrient reserves stored in the cotyledons, bypassing the usual requirement for endosperm development. This bypass of the endosperm requirement is highly unusual.

Discovery of parthenogenesis in sunflower introduces a previously unrecognized reproductive pathway in a major global crop. Researchers demonstrated that haploid seeds can develop without fertilization and be converted into fully fertile plants, offering a faster route to inbred line development.

The results provide a foundation for a scalable doubled haploid breeding system in sunflower, with the potential to accelerate crop improvement and expand global breeding capabilities.