Roche will partner with Zealand Pharma to co-develop and co-commercialize Zealand’s petrelintide for overweight and obesity indications, the companies said, through a collaboration and licensing agreement that could generate more than $5.3 billion for the Danish biotech.

Petrelintide is an amylin analog intended for once-weekly subcutaneous administration, and allowing for co-formulation and co-administration with other peptides since it has been designed with chemical and physical stability with no fibrillation around neutral pH.

“We strongly believe that petrelintide holds potential as a foundational therapy for weight management, addressing unmet medical needs among the majority of people living with overweight and obesity, both as a stand-alone therapy and in combination with other agents,” Adam Steensberg, Zealand’s president and CEO, said in a statement. “This collaboration with Roche is a step change to realize this vision, while solidifying Zealand Pharma as a key player in the future management of obesity.”

Investors largely appeared to share Steensberg’s optimism. Shares of Zealand traded on Nasdaq Copenhagen surged 38% from DKK 488.80 ($71.54) to an even DKK 674 ($98.38), while Roche shares traded on the SIX Swiss Exchange rose about 4% from CHF 296.50 ($335.83) to CHF 307.30 ($348.38).

“We commend management for identifying Roche as the partner for lead asset petrelintide,” Andy T. Hsieh, PhD, a biotech-focused research analyst with William Blair, wrote in a research note. “Roche’s clinical development prowess and global commercial infrastructure, we now hold a more bullish view on the prospect of petrelintide emerging as an important therapeutic intervention for chronic weight management.”

Hsieh reiterated Blair’s “Outperform” rating on Zealand stocks.

The companies cited clinical and preclinical data showing amylin receptor activation to reduce body weight by restoring sensitivity to the satiety hormone leptin, inducing a sense of feeling full faster. As a result, Roche and Zealand reason, petrelintide could deliver weight loss comparable to glucagon-like peptide 1 (GLP-1) receptor agonists but without the side effects associated with GLP-1 drugs.

Speaking with CNBC, Steensberg said Zealand launched talks with potential partners last year and had received a “high degree of interest” from several companies. Roche was “by far the most desirable,” citing its past activity in obesity drug development, including its acquisition of Carmot Therapeutics for up to $3.1 billion, completed in January 2024.

Steensberg added that Zealand was unlikely to have partnered with the market leaders in GLP-1 drug development, Novo Nordisk and Eli Lilly, reasoning that both companies were too tied to their existing multi-billion-dollar blockbuster obesity/diabetes franchises. Novo Nordisk markets semaglutide for adult type 2 diabetes as Ozempic® and for obesity as Wegovy®, while Eli Lilly markets tirzepatide for type 2 diabetes as Mounjaro® and for obese or overweight adults as Zepbound®.

Under study

Petrelintide is under study in a pair of Phase IIb clinical trials:

• ZUPREME-1 (NCT06662539), assessing the drug in obese/overweight people without type 2 diabetes (T2D) and launched in December 2024.

• ZUPREME-2, which will evaluate the drug in obese/overweight people with T2D when initiated later in the first half of this year.

Roche and Zealand agreed to co-develop and co-commercialize petrelintide both as monotherapy and in potential combinations in the United States and Europe, including a combo of petrelintide and CT-388, Roche’s lead incretin asset and a GLP-1/GIP [gastric inhibitory polypeptide] receptor dual agonist designed for once-weekly subcutaneous injection.

CT-388 is under study in Phase IIb clinical trials as a treatment for overweight/obesity patients with and without T2D. Roche inherited CT-388 when it acquired Carmot.

According to Roche, CT-388 was designed to have both potent activity on both the GLP-1 and GIP receptors and minimal to no ß-arrestin recruitment on either receptor. Such signaling significantly minimizes receptor internalization and consequent desensitization, which is expected to lead to prolonged pharmacological activity, the companies reason.

“We share the vision to develop petrelintide as a future foundational therapy,” stated Teresa Graham, CEO of Roche Pharmaceuticals. “By combining petrelintide with our Pharmaceuticals portfolio and with our Diagnostics expertise in cardiovascular and metabolic diseases, we are aiming to transform the standard of care and positively impact patients’ lives.”

Through the collaboration, while Roche and Zealand will co-commercialize petrelintide in the United States and Europe, Roche will obtain exclusive rights to commercialize the drug in the rest of the world, and be responsible for commercial manufacturing and supply.

Roche has agreed to pay Zealand $1.65 billion cash upfront—of which $1.4 billion will be due when the deal closes, and the remaining $250 million to be due over the first two anniversaries of the collaboration.

Zealand is also eligible to receive up to $1.2 billion in payments tied to achieving development milestones—primarily linked to the launch of Phase III trials with petrelintide monotherapy—as well as up to $2.4 billion in sales-based milestones, and tiered double-digit royalties up to high teens percentages on net sales in the rest of the world.

“A good partner”

“Roche’s global reach and ambitions in the CVRM [cardiovascular, renal and metabolism] therapeutic area make it a good partner for petrelintide, in our view,” Lucy Codrington, MBChB, equity analyst with Jefferies, wrote in a research note.

Codrington noted that her firm currently forecasted $10 billion in worldwide petrelintide peak sales at 60% probability for a share price of DKK 390 net present value (the value of all future cash flows, positive and negative, over the entire life of an investment discounted to the present).

The Roche-Zealand collaboration exceeds the value projected by her firm of a potential partnership deal for petrelintide of up to $4.25 billion in upfront and potential milestones, plus tiered royalties of 12–22% on worldwide net sales.

However, Zealand agreed to pay Roche $350 million, offsettable against milestone payments, for the petrelintide/CT-388 fixed-dose combination product or next-generation petrelintide combination products the companies have agreed to develop through the collaboration.

Roche and Zealand have also agreed to share profits and losses for petrelintide and the petrelintide/CT-388 combination 50/50 in the United States and Europe.

The transaction is set to close in the second quarter, subject to regulatory approvals and other customary closing conditions.

Celonic Group, a Swiss-based CDMO, is integrating Merck’s Breez™ micro-bioreactor platform into its process development operations. This addition will further enhance Celonic’s capabilities in monoclonal antibody (mAb) development and manufacturing by enabling highly efficient, scalable perfusion-based bioprocessing from early-stage development to large-scale manufacturing, according to Samanta Cimitan, PhD, CEO of the Celonic Group.

The Breez 2 mL micro-bioreactor platform is a fully automated, functionally closed, and continuous perfusion cell culture system. By incorporating Breez into its process development, Celonic aims to accelerate upstream process optimization while reducing cost of goods per gram and increasing operational efficiency, continued Cimitan.

“This technology integration marks a significant milestone in our pursuit of innovative bioprocessing solutions,” Cimitan said. “By leveraging the Breez platform, we can enhance our ability to develop and manufacture biologics with the aim of increasing productivity, reducing the cost of goods per gram ultimately benefiting our clients and patients worldwide.”

Exogenus Therapeutics and Lonza agreed to collaborate on the development of Exo-101, Exogenus’ exosome-based lead candidate. The company specializes in the development of therapeutics based on extracellular vesicles, including exosomes and other nanotechnologies.

Exo-101, derived from immunologically privileged cells from umbilical cord blood, has been shown to have regenerative, anti‑inflammatory, and immunomodulatory properties in multiple preclinical models and is expected to reach patients in 2027, according to an Exogenus spokesperson, who added that its multifactorial mode-of-action, mediated by a cocktail of small RNAs, proteins and anti-inflammatory lipids, provides the foundation for the drug’s therapeutic potential and positive safety profile.

Tissue regeneration and inflammatory disease

Exo-101 targets patients lacking effective treatment options primarily in the areas of tissue regeneration and inflammatory diseases. Lonza will leverage its expertise in exosome development and analytical services from its Siena (IT) site and dedicate a team of experts to define a GMP-compliant process for Exo-101 production. This feasibility effort aims to define the path toward Exo-101 manufacturing for clinical supply.

“We are committed to developing innovative, safe, and effective therapies in areas of high unmet medical needs, and to establishing new uses for biological waste materials,” said Joana Correia, co-founder and CEO, Exogenus Therapeutics. “This collaboration with Lonza will be essential to achieve a robust, GMP-compliant process for Exo-101 manufacturing, as we progress toward clinical studies.”

”We continue to pioneer this emerging and promising field of exosomes, leading innovation to provide development and manufacturing services for our partners,” added Davide Zocco, head of exosomes development at Lonza. We look forward to collaborating with Exogenus Therapeutics to advance its lead candidate toward the clinic.”

The overall economic outlook for 2025 may show slow-but-steady growth—”above-potential GDP growth toward 2.2%,” according to EY—but the job forecast is more optimistic for the life sciences sector, which is expected to maintain record-high employment in 2025 after achieving an all time high of more than 2.1 million workers last October.

While employment growth in the pharmaceutical and medicine manufacturing subsector has stayed sluggish, that performance has been offset by record-high employment in the Biotechnology R&D subsector, commercial real estate firm CBRE found in its February 5 “U.S. Life Sciences Outlook 2025” report.

Between January and October 2024, Biotech R&D companies added 10,700 employees, for an increase of 3.7% that has propelled the subsector to a record workforce size of 303,000. Biotechnology R&D growth has been driven by advances in cell and gene therapy development, building on breakthroughs that had already yielded a jobs boom between 2012 and 2022.

This A-List contains 10 research and clinical biotech occupation categories projected to add jobs through 2033, according to the U.S. Bureau of Labor Statistics (BLS)’s Occupational Outlook Handbook, which was mostly updated last August, though additional information about biological technicians, epidemiologists, and medical scientists was added in December.

The occupation categories are ranked in order of the number of additional jobs that are expected to be created between 2023 and 2033.

Each occupational category is listed with BLS-calculated metrics that include the number of jobs in 2023, the percentage increase between 2023 and 2033, and the median pay per year in 2023. Accompanying these metrics is a BLS occupational description.

This year, as with GEN’s A-Lists of top biopharma jobs in demand published in 2024 as well as our 2023 A-List, the greatest number of projected jobs over the coming decade were for clinical laboratory technologists and technicians (also called medical laboratory scientists), i.e., professionals who collect samples and perform tests to analyze body fluids, tissue, and other substances.

Eight of the top 10 occupations highlighted in this A-List showed year-over-year increases in job openings projected over the next decade as compared with last year’s A-List—a clear improvement from last year, when 7 of the 10 occupations showed year-over-year declines in job openings. That appears to reflect  increased hiring plans by life-sci employers across industry and academia despite ongoing concerns over the broader economy.

The largest drop in the employment change projected for 2023–2033 is among epidemiologists, whose projected number of jobs a decade from now was calculated by BLS at 2,100, down 22% from 2,700 last year. While no explanation was offered, one possible reason may be a reduced research emphasis on COVID-19 and future pandemics. Fortunately, epidemiology is the only occupation showing a projected one-year decrease. Genetic counselors showed the same number of projected jobs this year as last (600), and all other occupations showed increases ranging from 8% (clinical lab technologists) to 68% (chemical technicians).

1. linical Laboratory Technologists (Medical Laboratory Scientists) and Technicians

Projected employment change, 2023–2033: 18,200 more jobs

Job openings projected each year on average, 2023–2033: 24,200

Number of jobs, 2023: 344,200

Job outlook, 2023–2033: 5% (Faster than average)

Median pay, 2023: $60,780/year

About the position: Clinical laboratory technologists (also known as medical laboratory technologists) and clinical laboratory technicians (also known as medical laboratory technicians) perform medical laboratory tests for diagnosis, treatment, and prevention.

2. Medical Scientists

Projected employment change, 2023–2033: 16,800 more jobs

Job openings projected each year on average, 2023–2033: 8,900

Number of jobs, 2023: 146,600

Job outlook, 2023–2033: 11% (Much faster than average)

Median pay, 2023: $100,890/year

About the position: Medical scientists conduct research aimed at improving overall human health. They often use clinical trials and other investigative methods to reach their findings.

3. Biological Technicians

Projected employment change, 2023–2033: 5,500 more jobs

Job openings projected each year on average, 2023–2033: 10,300

Number of jobs, 2023: 83,100

Job outlook, 2023–2033: 7% (Faster than average)

Median pay, 2023: $51,430/year

About the position: Biological technicians help biological and medical scientists conduct laboratory tests and experiments.

4. Biochemists and Biophysicists

Projected employment change, 2023–2033: 3,200 more jobs

Job openings projected each year on average, 2023–2033: 3,100

Number of jobs, 2023: 35,700

Job outlook, 2023–2033: 9% (Much faster than average)

Median pay, 2023: $107,460/year

About the position: Biochemists and biophysicists study the chemical and physical principles of living things and of biological processes, such as cell development, growth, heredity, and disease.

5. Chemical Technicians

Projected employment change, 2023–2033: 3,200 more jobs

Job openings projected each year on average, 2023–2033: 7,300

Number of jobs, 2023: 58,300

Job outlook, 2023–2033: 5% (As fast as average)

Median pay, 2023: $56,750/year

About the position: Chemical technicians use laboratory instruments and techniques to help scientists analyze the properties of materials.

6. Epidemiologists

Projected employment change, 2023–2033: 2,100 more jobs

Job openings projected each year on average, 2023–2033: 800

Number of jobs, 2023: 11,000

Job outlook, 2023–2033: 19% (Much faster than average)

Median pay, 2023: $81,390/year

About the position: Epidemiologists are public health workers who investigate patterns and causes of disease and injury.

7. Microbiologists

Projected employment change, 2023–2033: 1,600 more jobs

Job openings projected each year on average, 2023–2033: 1,900

Number of jobs, 2023: 23,200

Job outlook, 2023–2033: 7% (Faster than average)

Median pay, 2023: $85,470/year

About the position: Microbiologists study microorganisms such as bacteria, viruses, algae, fungi, and some types of parasites.

8. Bioengineers and Biomedical Engineers

Projected employment change, 2023–2033: 1,500 more jobs

Job openings projected each year on average, 2023–2033: 1,400

Number of jobs, 2023: 19,700

Job outlook, 2023–2033: 7% (Faster than average)

Median pay, 2023: $10,730/year

About the position: Bioengineers and biomedical engineers combine engineering principles with sciences to design and create equipment, devices, computer systems, and software.

9. Zoologists and Wildlife Biologists

Projected employment change, 2023–2033: 800 more jobs

Job openings projected each year on average, 2023–2033: 1,500

Number of jobs, 2023: 18,800

Job outlook, 2023–2033: 4% (As fast as average)

Median pay, 2023: $70,600/year

About the position: Zoologists and wildlife biologists study animals—those both in captivity and in the wild—and how they interact with their ecosystems.

10. Genetic Counselors

Projected employment change, 2023–2033: 600 more jobs

Job openings projected each year on average, 2023–2033: 300

Number of jobs, 2023: 3,500

Job outlook, 2023–2033: 16% (Much faster than average)

Median pay, 2023: $95,770/year

Bristol Myers Squibb (BMS) plans to buy out its partner in developing the blockbuster multiple myeloma drug Abecma® (idecabtagene vicleucel), by agreeing to acquire 2seventy bio for approximately $286 million, the companies said.

The deal, announced late Monday, caps a turbulent three years for 2seventy bio. The company served as the oncology business of Bluebird Bio until Bluebird spun out 2seventy in 2021. Bluebird’s longtime CEO or “chief Bluebird” Nick Leschly served as 2seventy’s first CEO or “chief kairos officer” until he stepped down last year when current CEO Chip Baird’s appointment took effect, with Leschly becoming chairman.

The turnover at the top followed 2seventy’s inability to reverse net losses that reached $217.57 million in 2023, on revenue of just $100.387 million. 2seventy responded in September 2023 with a restructuring that eliminated 40% of its workforce, followed by an additional 14% workforce reduction (about 30 jobs) in January 2024 after the company narrowed its focus exclusively to commercialization and further development of Abecma with BMS.

Abecma is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy that first won FDA approval in 2021 as the first FDA-approved chimeric antigen receptor T cell (CAR T) cell therapy indicated for relapsed or refractory multiple myeloma following four or more lines of therapy. Following a label expansion last year, Abecma is now indicated to treat adults with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

The companies oversee a clinical development program for Abecma that includes two ongoing clinical studies in earlier lines of treatment for patients with multiple myeloma, KarMMa-2 (NCT03601078) and KarMMa-3 (NCT03651128).

Reduced red ink

2seventy’s narrowing of focus, plus job cuts, helped reduce the company’s red ink for the first nine months of 2024 to a net loss of $37.727 million, compared with a $160.748 million net loss for January–September 2023.

Abecma generated U.S. revenue of $242 million in 2024, within 2seventy’s earlier-issued guidance to investors of between $240 million and $250 million. U.S. commercial revenue is split between 2seventy and BMS, which said U.S. revenue fell 32% from 2023.

“A year ago, 2seventy decided to exclusively focus on unlocking the value of Abecma, with the goal of delivering more time for people living with multiple myeloma and maximizing value for all stakeholders,” Baird said in a statement. “We believe that Abecma will continue to benefit from BMS’ experience and resources to ensure this important therapy is delivered to patients who need it.”

Leerink Partners analyst Daina M. Graybosch, PhD, expressed more caution on the BMS-2seventy combination.

“BMY’s acquisition of 2seventy bio (TSVT) shows modest confidence in the near-term profit potential of the companies’ shared autologous BCMA CAR-T Abecma (ide-cel),” Graybosch wrote in a research note. “By our estimates, BMY could realize a return in as little as two years, based on saved profit-sharing expenses payable to 2seventy (as part of their prior partnership agreement).

While the deal value of $286 million is 41% below Leerink’s prior discounted cash flow valuation of $487 million for 2seventy, “we do not expect that an alternative acquirer will emerge, and expect that the transaction with BMY will close,” Graybosch predicted. “2seventy has been successful since their 2023 reorganization in optimizing their business for strategic optionality, but their focus has been on trimming the cost base.”

BMS will need to consider a competitive challenge for Abecma, the Leerink analyst cautioned, citing the expected 2026 launch of “anito-cel” by Kite, a Gilead company, and Arcellx.

“Thus far, anito-cel has an efficacy profile in line with market leader Carvykti, and movement neurotoxicity (MNT) safety profile in line with Abecma—threatening Abecma’s niche as the option for patients who want to avoid the risk of MNTs like Parkinsonism,” Graybosch added. She downgraded the firm’s rating on 2seventy from “Outperform” to “Market Perform” and lowered its 12-month price target from $9 to $5 a share.

Bluebird Bio last month entered into a definitive agreement to be acquired by funds managed by publicly-traded Carlyle and privately-held SK Capital Partners, partnering with a team of veteran biotech executives led by former Mirati Therapeutics CEO David Meek.

Shrinking workforce

2seventy’s workforce shrunk from 437 full-time employees as of March 1, 2022, about a year after the spinout was completed, to 425 full-time employees as of February 1, 2023, to 274 employees the same day a year later, according to Form 10-K annual reports filed with the U.S. Securities and Exchange Commission.

In addition, 2seventy shed 160 jobs last year when it sold its cell therapy pipeline and operations to Regeneron Pharmaceuticals for at least $15 million, including its bbT369 program in b-cell non-Hodgkin lymphoma (b-NHL), its SC-DARIC33 program in acute myeloid leukemia (AML), MUC16 in ovarian cancer, a T-cell receptor (TCR) program targeting MAGE-A4 in cancers, and several unnamed targets. Regeneron transformed the assets into a new Regeneron Cell Medicines business led by 2seventy’s former CSO Philip Gregory.

In December, Regeneron paid a $1 million milestone payment to Medigene, whose end-to-end platform generated the TCRs applied in Regeneron’s MAGE-A4-TCR program. The payment followed an unspecified development milestone for the program occurring in a clinical trial in China led by JW Therapeutics, a prior collaborator of 2seventy bio—the first clinical use of the platform, Medigene stated at the time.

At $5 per share, the acquisition deal represents an 88% premium to 2seventy’s closing stock price of $2.66 on Friday. While the deal has a total equity value of approximately $286 million, the net value shrinks to $102 million after accounting for 2seventy’s approximately $184 million of cash, cash equivalents, and marketable securities as of December 31, 2024, disclosed last month.

BMS said it will begin a tender offer to acquire all outstanding shares of 2seventy bio in an all-cash transaction unanimously recommended by 2seventy’s board. The companies said stockholders owning approximately 5.3% of 2seventy’s outstanding shares have agreed to tender all of their owned shares in the offer.

The acquisition is expected to close in the second quarter subject to customary closing conditions, including the tender of most of the outstanding shares of 2seventy’s common stock and the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976.

Upon successful closing of the tender offer, BMS said it will acquire all remaining shares of 2seventy’s common stock that are not tendered in the tender offer through a second-step merger at the same $5 per share as the tender offer. 2seventy’s common stock will no longer be listed for trading on Nasdaq.

2seventy investors roared their approval of the deal by sending the company’s shares rocketing 77% from $2.80 to $4.95 Tuesday. BMS shares dipped 2.5%, from $63.11 to $61.51.

“The strategic rationale for this acquisition is clear and today’s announcement represents the culmination of the journey for 2seventy bio,” Baird added.a

Given the growing antibiotic resistance crisis, novel ways to target bacterial infections are becoming increasingly important. One potential strategy is to manipulate bacterial genes at the transcriptional level by silencing their resistance genes. However, siRNAs have not been applied to regulate bacterial genes due to the lack of RNAi regulatory machinery, i.e., RNA-induced silencing complexes (RISCs), in bacteria. In addition, efficient methods for delivering siRNAs to bacteria in vivo are not currently available.

In a new study, researchers demonstrate that exosomes can serve as delivery vehicles to introduce AGO2-loaded siRNA into the cytoplasm of bacteria which downregulate gene expression of the mRNA that shares sequence complementarity to the siRNA.

This work is published in Cell Reports Medicine in the paper, “siRNA-AGO2 complex inhibits bacterial gene translation: a promising therapeutic strategy for superbug infection.”

Despite the fact that the siRNA machinery is absent in prokaryotes, this study demonstrates that exosomal siRNAs can be efficiently delivered into bacteria and silence target bacterial genes. The exosomal Argonaute 2 (AGO2) protein forms a complex with siRNAs, which is essential for siRNA-mediated gene silencing in bacteria. Even though the delivered siRNA was designed to possess full sequence complementarity to the bacterial mRNA, downregulation of the target protein was achieved at the translational level rather than on the level of mRNA stability (as would be expected in mammalian systems).

Exosomal siMecA (an siRNA designed to target the mecA gene) can downregulate the mecA gene which encodes the penicillin-binding protein 2a (PBP2a), a protein at the heart of the drug-resistance phenotype in MRSA. Both in vitro and in vivo (using MRSA-infected mice) data demonstrated that by reducing PBP2a levels by exosome-delivered siRNA-AGO2 complex, MRSA can be converted into methicillin-sensitive bacteria.

To induce exosome production in vivo, the authors demonstrated that by intravenous injection of a plasmid encoding all relevant genes for the production of a particular siRNA into mice, the mouse liver was producing siRNA-AGO2 loaded exosomes (siMecA-Exos) efficiently targeting MRSA. These findings have potential clinical relevance since it might be possible to use this approach to also target multi-drug resistant bacterial infections in the human system.

Exosome-mediated small RNA-AGO2 transport and bacterial gene silencing is a potential pathway by which mammalian cells regulate interacting bacteria in vivo. This is demonstrated in the treatment of MRSA infection by mouse liver-produced siMecA-Exos. In addition, exosome-mediated RNAi may function with imperfectly matched sequences, so exosomal miRNAs, which have multiple bacterial targets with imperfect base pairing, may regulate bacterial genes in the same way as exosomal siRNAs. It is intriguing to consider the possibility that mammalian hosts employ exosomes to transport molecules with biological functions to the mammalian microbiome for interspecies communication and regulation under physiological conditions.

 

Testifying before the Senate Health, Education, Labor, and Pensions (HELP) Committee on Thursday, President Donald Trump’s nominee for FDA Commissioner Martin A. Makary, MD, sought to assure senators that if confirmed, he would support efforts to expedite reviews of new drugs indicted for rare diseases, as well as tailor to individual diseases the agency’s regulatory review-to-approval pathways designed to advance drugs to treat them.

“We have to customize the regulatory process to the condition that we’re trying to be able to offer hope, so, if a condition affects 19 people in the world as a partial triplication chromosome 15 disorder does, or a disease that affects 52 kids in the world, we cannot require two randomized control trials,” Makary said, responding to a question from Sen. Lisa Murkowski (R-AK), according to a transcript released by her office. “We have to customize the regulatory process to what we’re trying to do if our goal is to try to provide safe and effective therapies.”

Makary, a surgeon and public policy researcher at Johns Hopkins University, was nominated “to course-correct and refocus the agency,” Trump said last November in announcing his choice to helm the FDA. Should he be confirmed, Makary would report to Health and Human Services (HHS) Secretary Robert F. Kennedy Jr., who has targeted the FDA for drastic changes on a host of biopharma and broader healthcare concerns as part of his commitment to “make America healthy again” by “go(ing) wild on health.”

“If confirmed, I hope to ensure the FDA holds to the gold standard of trusted science, transparency, and common sense to rebuild public trust and make America healthy again,” Makary said in his opening statement.

Murkowski noted that Makary has committed to pursuing regulatory decisions that are based on both science and “common sense.”

“How do we define common sense here as it applies to the regulatory decisions of the FDA?” Murkowski asked Makary. “How do we make sure that ALS patients who are looking at a very, very limited time frame, they can’t wait for the traditional approval process, there are some emerging measures using digital technologies, is this in your realm of common sense?”

A renewed focus on speeding up rare disease reviews could shore up the stocks of rare disease drug developers—15 of which have seen their share prices slide so far this year, according to analysts at Jefferies.

Analyst sees “clear +” for stocks
“A clear + [positive] for the broader space,” Jefferies equity analyst Andrew Tsai wrote Thursday in a research note following Makary’s testimony.

The average decline of the stocks tracked by Jefferies was 18%, with a median decline of 21%. Falling the furthest since the start of January was Lexeo Therapeutics (NASDAQ: LXEO), which has plummeted 59.5% from $6.67 on January 2 to $2.70 at the closing bell Friday—a slight improvement over the 62% plunge cited by Jefferies as of Wednesday.

Lexeo late last year reached an agreement with the FDA on key elements of a registrational development plan for LX2006, an AAV-based gene therapy delivered intravenously for the treatment of Friedreich’s ataxia (FA) cardiomyopathy. The plan includes an accelerated approval pathway that sets as co-registrational endpoints both left-ventricular mass index (LVMI) and frataxin protein expression. Target levels include 10% reduction in LVMI and 40% frataxin positive area as measured by immunohistochemistry.

In January at the J.P. Morgan 43^rd Annual Healthcare Conference, Lexeo said it expected to release data in mid-2025 from patients given the highest of three dosages of LX2006 in the current Phase I/II trial (NCT05445323), with plans to potentially launch a registrational study by the end of this year or early 2026.

Lexeo has also generated positive interim Phase I/II data for another program, LX1001 for the treatment of APOE4-associated Alzheimer’s disease, presented last fall at the Clinical Trials on Alzheimer’s Disease (CTAD) conference. But by January, the company said continued development of LX1001 would hinge on its ability to find a partner—a development that set Lexeo’s stock on a downward path this year.

The second biggest decline was the 47% nosedive by shares of Dyne Therapeutics (NASDAQ: DYN) from $25.46 on January 2 to $12.40 on Friday. That decline was kicked off when the company reported data from its ongoing Phase I/II ACHIEVE trial (NCT05481879) assessing one of its two lead candidates, DYNE-101, in patients with myotonic dystrophy type 1 (DM1).

While Dyne showed splicing correction and robust and sustained functional improvements in DM1 patients dosed with DYNE-101, the extent of improvement was less than investors hoped, and shares tumbled 31% on January 10 as a result. Dyne has since enrolled patients in a registrational expansion cohort of ACHIEVE that is expected to achieve full enrollment by mid-2025, and whose data will support a planned accelerated approval submission to the FDA.

Brain drain fears

In addition to overall macroeconomic conditions, the analysts said, the rare disease stock declines reflect fears of a brain drain by industry professionals (and thus investors) that numerous officials will exit the FDA in coming weeks, including experienced reviewers specializing in studying rare disease drugs.

That fear was heightened last month when Patrizia Cavazzoni, MD, resigned as director of the FDA’s Center for Drug Evaluation and Research (CDER), and returned to Pfizer to become its chief medical officer. “We are not sensing FDA review/meeting delays but are certainly monitoring for noticeable changes,” Tsai wrote Wednesday in a second research note.

Tsai noted that if confirmed, Makary could name a permanent successor to Cavazzoni at CDER, which is now helmed by an acting director, Jacqueline Corrigan-Curay, JD, MD. CDER is one of two FDA centers that oversee rare disease reviews, the other being the Center for Biologics Evaluation and Research (CBER).

Since 1992, CDER has granted 328 accelerated approvals—21 of them last year alone—while CBER granted 24 accelerated approvals between 2000 and 2022.

“Many public sources have indicated many more staff at the FDA are considering resignation or various buyout offers, etc., putting risk on FDA capacity and resources especially ahead of increasing numbers of drug filings and reviews, i.e., PDUFAs this year,” Jefferies equity analyst Michael J. Yee wrote in a March 5 research note. Yee used the acronym for the Prescription Drug User Fee Act, the regulation through which the FDA sets target decision dates for its reviews of new drugs and biologics.

Policy questions

In his testimony, Makary touched on numerous topics raised by HELP committee senators, including probationary employee layoffs at the FDA (he committed to assessing the agency’s staffing and personnel levels), the postponement of a Vaccines and Related Biological Products Advisory Committee meeting (he did not commit to rescheduling), and clinical trial diversity (while saying he was supportive, he added he was unfamiliar the agency’s removal of website pages focused on diversity, equity, and inclusion).

But Makary also signaled he intends to delve into big-picture policy questions going beyond drug development in rare diseases and other indications—from the length of reviews, to whether new treatments and devices should require prescriptions.

“We can use some common sense to ask some big questions we’ve never asked before at the FDA. Why does it take 10 years for a drug to get approved?” Makary said. “Why does a college student who suffers from chronic abdominal pain for years, and we have no idea what’s going on, and they go to Italy for a summer and they are suddenly cured of their abdominal pain? Why does a peanut allergy medication that’s been safe with data for decades get approved in Europe before the United States when nearly 10% of our population has a food allergy”

“I do think there’s a lot of areas where we can ask, does a drug need to be prescription, when it could be over the counter?” Makary continued. “Why are we requiring continuous glucose monitors to have a doctor’s prescription when it’s good for people to use these monitors and learn about what they’re eating? We don’t just want to limit continuous glucose monitoring to people with diabetes. We want to prevent diabetes when 30% of our nation’s children have diabetes or pre-diabetes or some form of early insulin resistance. Why are we holding these tools to help people, empower them about their health, until after they’re sick? Same with continuous blood pressure monitoring.”

Leaders and laggards

• Moderna (NASDAQ: MRNA) shares climbed 16% from $30.37 to $35.21 Wednesday after president Stephen Hoge, MD, said a late-stage trial assessing mRNA-4157/V940, the adjuvant melanoma vaccine Moderna is co-developing with Merck & Co. (NYSE: MRK) was fully enrolled, and restated that the companies were aiming to receive full FDA approval in 2027. “Having it fully enrolled and knowing the natural history of when we’d expect those events to be, we’re cautiously optimistic. ’27 is right on path,” Hoge told attendees Wednesday at the TD Cowen 45th Annual Health Care Conference 2025, held in Boston, as reported by Seeking Alpha. mRNA-4157/V940 is a messenger RNA (mRNA)-based individualized neoantigen therapy (INT) for which the companies last fall projected approval in 2027, followed by launch in 2028.
• Plus Therapeutics (NASDAQ: PSTV) shares more than quadrupled, zooming 311% from 35 cents to $1.44 Thursday after the developer of targeted radiotherapeutics with advanced platform technologies for central nervous system cancers announced that the FDA granted its Orphan Drug Designation to Rhenium (¹⁸⁶Re) Obisbemeda for the treatment of leptomeningeal metastases (LM) in patients with lung cancer. The designation Plus’ completion of the ReSPECT-LM Phase I single-dose trial (NCT05034497), which established a recommended dose for Phase II studies. Plus is advancing a Phase II single-dose expansion trial and a Phase I multiple-dose trial and said it is actively engaging the FDA to define an optimal pivotal trial strategy.

Kaileigh Baia still likes to play trivia-style games, though her memory recall is slower than it used to be before COVID-19.

She still gets to the gym. Last year she ran a 5K. However, it is important to pace herself now due to asthma-like breathing difficulties and being susceptible to more significant fatigue after activities.

It’s been more than four years since the 27-year-old Grand Rapids woman had her first bout with COVID-19. The illness caused lung inflammation, joint pain, damaged her vocal cords, left some of her favorite foods tasting and smelling rotten, and forced her to spend two weeks sleeping upright with breathing difficulties.

Baia is among the millions of Americans who have been diagnosed with long COVID, a complex, multisystem disorder associated with COVID-19 symptoms lasting longer than 90 days.

The most common symptoms of long COVID are fatigue; loss of sense of smell or taste; memory loss, brain fog, or disorientation; shortness of breath; general weakness; muscle weakness; joint pain; and hair loss.

Baia, a hospital referral coordinator, visited specialists and tried various therapies, attempting to regain the life she had before October 2020. As of March — 53 months after getting infected with coronavirus (SARS-CoV-2) — she feels 85% to 90% recovered.

It’s been five years since the novel coronavirus rocked the world, killing millions of people, hospitalizing countless others, causing an economic crisis, and changing peoples’ day-to-day lives for the better part of three years.

Monday, March 10, marks the five-year anniversary of Michigan’s first reported cases of COVID-19. The death toll over five years is more than 39,760, according to state health records.

An estimated 20% of adults infected with COVID in 2020-2022 reported symptoms lasting 90 days or more, said Nancy Fleischer, a professor of epidemiology at the University of Michigan. National data estimated about 5% to 7% of all adults were experiencing long COVID in 2024.

Coronavirus isn’t the first virus to cause long-lasting effects. Other viruses like Epstein-Barr and West Nile have been associated with the chronic fatigue lasting weeks or months after infection.

“The reason long COVID became so prevalent is SARS-CoV-2 was so novel, there wasn’t a lot of immunity, and a lot of people experienced it at once,” Fleischer said. “Usually, people are infected with viruses at different times and with different levels of immunity.”

There’s been significant research on post-COVID conditions, ranging from their prevalence in various communities and which populations are most affected, to the physiological mechanisms causing the long-term effects.

Yet, many questions remain unanswered.

Years of not knowing what’s wrong or how to fix it has been challenging for those like Jennifer Gansler, 56, who felt left in the dark by medical experts who ran numerous tests but found little of significance to explain what ailed her.

“This whole idea of not getting better wasn’t on anybody’s radar,” said Gansler, an academic advisor at Michigan State University. “I struggled to find support in the medical community, and I had to do a lot of my own research.

“It’s been a lot of false starts, a lot of trial and error.”

Blazing your own trail

Gansler was among Michigan’s first confirmed cases of COVID-19. Following a trip to Spain, she got sick March 11, 2020, the same day the World Health Organization declared coronavirus a pandemic.

A self-described “super active, outdoors-y person,” she was an otherwise healthy mother who liked to run and hike, having tackled both the Porcupine Mountains and Chicago Marathon in 2019.

Her case of COVID didn’t require hospitalization, though she did visit an emergency room twice for breathing problems. She recovered at home in isolation, slowly waiting to get better.

After five months, she estimated she was 30% recovered. Crushing fatigue made it hard to get out of bed. She had chest tightness, a persistent cough, joint and muscle pain, and hair loss.

Simple tasks like taking a shower or talking on the phone left her winded. The prospects of running again seemed impossible.

Gansler worked with a chronic fatigue doctor. She tried supplements and medications. Everything she did made her crash, sending her back to bed.

For both Gansler and Baia, looking to others dealing with similar long-term symptoms made them feel less alone and offered glimpses hope for improvement.

Evolution of care

During much of the COVID pandemic, assessment of long COVID followed the traditional medical model of care, said Dr. Katharine Seagly, co-director of the Post-COVID Conditions Clinic at the University of Michigan.

Physicians would order blood tests, MRIs, CT scans and other screenings, attempting to find the exact mechanisms causing continued symptoms in patients. It was an expensive process with little value for patients like Gansler, who often felt they weren’t being heard or believed by doctors as test results came back normal.

“All these experts were seeing patients and running tests and finding a lot of nonsignificant results, which wasn’t a particularly helpful approach,” Dr. Seagly said.

“The idea of ‘I need a doctor to fix me,’ we know that’s not a helpful way of thinking about chronic conditions. Being able to have that sense of autonomy and self-management for chronic medical conditions is key for patient wellbeing.”

Most long COVID clinics that focused on the traditional medical model closed their doors.

Where U-M’s Post-COVID Conditions Clinic differed is it pivoted to an approach that focused more on function, behavioral medicine and rehabilitation. That included things like rehab, exercise, behavioral and mental health interventions.

The model centers around a six-session post-COVID recovery group led by neuropsychological and rehab psychology providers who equip patients with the education, skills and interventions to address their current symptoms and optimize their quality of life.

Seagly said they no longer use the term “long COVID” because it implies someone still has the virus. They prefer “post-COVID conditions” because it indicates multiple conditions affecting each patient differently.

As of December, the clinic had seen more than 1,000 patients. Referrals aren’t as high as they were previously, but they’ve remained steady over the last year.

In the first directive since his nomination to secretary of health and human services, Robert F. Kennedy Jr. thrust psychiatric medications and their use among children into the national spotlight.

The Trump administration introduced the initiative “Make our Children Healthy Again Assessment” in a February executive order that aims, in part, to “assess the prevalence of and threat posed by the prescription of selective serotonin reuptake inhibitors, antipsychotics, mood stabilizers, stimulants, and weight-loss drugs” within 100 days.

Kennedy, who is not a physician and has no medical or public health training, has said that the class of drugs known as selective serotonin reuptake inhibitors, or SSRIs, are harder to give up than heroin, and that school shootings became prevalent only after the introduction of Prozac, a common SSRI drug. These statements are riddled with falsehoods, according to health organizations, psychiatrists and researchers.

Dr. Marcia Slattery, a physician and professor of psychiatry and pediatrics at the University of Wisconsin-Madison, focuses on anxiety disorders in patients between 5 and 18 years old. She could not speak to any of Kennedy’s claims, but offered her expertise on SSRIs and their role in children’s mental health.

Here’s what to know.

Serotonin is a neurotransmitter in our brains associated with mood and emotions, sleep, appetite and digestion, learning and memory, pain perception and even bone health. Neurotransmitters carry messages between nerve cells in the brain, called neurons.

Typically, once a signal is passed between neurons, serotonin is reabsorbed in those cells, a process called “reuptake.” SSRIs block this process of reuptake, which increases serotonin levels in your brain. That enables the brain to continue using serotonin to connect more dots as we go about everyday tasks.

Emotions also factor into how we think, problem solve and pay attention, Slattery said, and can affect the brain in ways that go beyond lifting some of the fog of depression and anxiety.

“Taking the medication basically is allowing the brain to operate in a healthy manner, in a normalized manner, that allows the kid to then engage,” Slattery said.

Prescribing medications is never the first step in treating children and adolescents, Slattery said.

The psychiatrist or pediatrician works to better understand the bigger picture of a child’s circumstances before taking out their prescription pad. A child’s school environment may trigger anxiety, learning problems and bullying. Family dynamics can also play a role.

That said, medication helps to normalize the brain of a child experiencing severe anxiety and depression, Slattery said, which can allow a child to move forward and function more effectively, whether at home, at school or in social settings.

“When we do use medication, it still should be in conjunction with all these other non-pharmacological interventions,” Slattery said. “That link gets lost a lot. People think all we’re doing is prescribing medications as soon as a kid comes in and says they’re anxious or they’re depressed. That’s not the case by a long stretch.”

SSRIs can be life-saving medications, Slattery said.

Just as a pediatrician wouldn’t ignore a child’s severe asthma attacks, a psychiatrist or pediatrician isn’t going to ignore signs of severe depression and anxiety, which are associated with higher risks of suicide and substance abuse, academic declines, decreased school performance, and “a lot of peer-social interaction problems,” Slattery said.

During the pandemic, alarms rang out from different pediatric health groups about the youth mental health crisis. COVID exacerbated the burgeoning crisis among children and adolescents.

Between January 2016 and December 2022, the monthly antidepressant dispensing rate increased by 66%, according to a 2024 study from the American Academy of Pediatrics. At the same time, however, the decision to prescribe SSRIs for children and adolescents for depression and/or anxiety was largely found to be appropriate, another study published in the American Academy of Pediatrics concluded.

The use of SSRIs aligns with a grimmer fact: teenagers say they’re more anxious, depressed and suicidal than they were prior to the pandemic. In Wisconsin, more than half of high schoolers reported having anxiety, 35% reported depression, 21% said they’ve intentionally harmed themselves, and 19% have considered suicide, according to the 2023 Youth Risk Behavior Survey.

Taking an SSRI doesn’t have an immediate effect on the brain. It’s a gradual change in the brain that targets a specific neurotransmitter, Slattery said.

“Literature would show that these are not addictive medications, and you’re not on them for life,” Slattery said.

Opiates like heroin activate the brain’s reward system, releasing the chemical dopamine, a hallmark of addiction that inspires feelings of euphoria and bliss.

SSRIs, by and large, only target serotonin and have little effect on dopamine.

Comparing serotonin receptor sites with opiate receptor sites “is night and day,” according to Sean Leonard, a psychiatric nurse practitioner from San Diego who focuses on addiction medicine told USA Today.

As with many medications, abrupt cessation can lead to symptoms of withdrawal according to the Canadian Medical Association Journal and are typically mild, producing flu-like symptoms, nausea and imbalance, among others.

After months of stable functioning in a patient, Slattery said she starts tapering down the dosage. In cases where anxiety crops up during that time, Slattery helps her patient use the skillsets developed in therapy to manage and cope with stress.

Slattery said it’s better to reframe this question. Has severe depression or anxiety changed who you know your child to be?

SSRIs will change a child like any medication would. But Slattery described the change more as a release.

“It’s like being unwrapped from cellophane. Your child is now able to experience the world and feel good about him or herself, and engage in life,” Slattery said. “And so you will notice a difference in your child, but in a healthy way.”

No.

Studies have yielded no causation between school shootings and psychotropic medications like SSRIs. A majority of school shooters had no history of taking these medications.

On the other hand, people with untreated serious mental illness are more likely to be victims of violence or self-inflict harm than be violent toward others.

 

Optum Rx, a pharmacy benefit manager owned by one of the country’s largest insurance companies, UnitedHealth Group, has added a new, much-anticipated pain drug to some of its commercial formularies.

Sold as Journavx, the drug received U.S. approval in late January as a treatment for the short-lived “acute” pain typically felt after an operation or accident. Journavx works differently than other available medications, and its developer, the biotechnology juggernaut Vertex Pharmaceuticals, has positioned it as an important, non-opioid option for pain management.

While doctors have welcomed this additional tool, and some analysts see it as a multibillion-dollar product, substantial commercial barriers could constrain patient access as well as sales. Cheap opioids have long dominated the pain drug market. At a list price of $31 a day, Journavx is many times more expensive than generic versions of drugs like hydrocodone.

Ahead of the drug’s approval, Stuart Arbuckle, Vertex’s chief operations officer, said price and access were the biggest issues stakeholders had raised in discussions on Journavx. Still, he said then that conversations with insurers were going well.

“We’re encouraged Optum has added Journavx to its formulary, reflecting the unmet need for new treatment options and the promise of Journavx in acute pain, and we continue to work with them and other payers to ensure broad availability,” Heather Nichols, a Vertex spokesperson, said in a statement.

Optum’s move, first reported by Bloomberg, appears to be the first significant, public update about Journavx coverage from a major commercial payer. Other healthcare giants, including CVS, Humana and Cigna, either declined or didn’t immediately respond to requests for updates on their coverage plans.

The team that crafts the list of prescription drugs that Optum covers is still evaluating the clinical data underpinning Journavx “and will make a recommendation on formulary placement soon,” according to Elizabeth Hoff, a spokesperson for Optum’s pharmacy care services division.

“In the interim, Journavx was added to our standard commercial formularies to allow immediate access to a non-opioid option for moderate-to-severe pain in the acute setting,” Hoff added.

Optum has, for now, put Journavx on “Tier 3” of its formulary, which is designated for “higher-cost brand name” drugs along with some generics. Optum notes that using lower tier or “preferred medications” can help lower out-of-pocket costs for patients.

Not long before Journavx’s approval, analysts at the investment firm Cantor Fitzgerald said they spoke to a senior director of product development at UnitedHealth Group. According to analyst Olivia Brayer, the director expected Journavx to receive broad coverage because insurers are under pressure to cover non-opioid pain medications.

He also did not anticipate Journavx having to go through “step therapy,” a controversial practice in which patients must “fail” on cheaper drugs before an insurer agrees to cover pricier medicines.

In a note to clients, Leerink Partners analyst David Risinger described UnitedHealth’s initial coverage as “encouraging.”

“Bottom line: We are pleased to see a major PBM cover Journavx ahead of its launch for acute pain,” Risinger wrote.

Medicaid plans in two states — New York and Arkansas — have also put policies in place for Journavx.