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STAT+: How a four-month FDA delay forced a small biotech company to close its doors

In February, a small biotech company called Kezar Life Sciences reached a breakthrough with the Food and Drug Administration, agreeing to a plan for a clinical trial it hoped could lead to the approval of its treatment for a rare, debilitating liver disease called autoimmune hepatitis. The problem: The agreement came four months too late.

The meeting to discuss trial design, a critical step in the drug development process, had been scheduled for last October. But the FDA abruptly canceled it without explanation. The company could no longer proceed as planned and, without clarity from regulators, its path forward was unclear. Kezar’s investors wanted out, and the biotech was forced to start the process of winding down.

It laid off most of its staff of about 60 people. Then, it auctioned off its lab equipment and sold much of its office furniture, except for the table and chairs in one conference room it kept in case the company got its meeting with FDA staff.

Last week — after the meeting and the breakthrough happened — the company said it would be sold. Kezar hopes the buyer, Aurinia Pharmaceuticals, will take the drug forward, though how quickly that can happen, if at all, is not guaranteed.

It’s also not clear why Kezar’s initial meeting was canceled. But to CEO Chris Kirk, the chain of events fits a pattern over the past year in which volatility at the FDA — including staff departures and decision-making seen as inconsistent — has ricocheted across the industry, impacting drugmakers. Those impacts can fall disproportionately on small companies, which, unlike major drugmakers, often operate on one financing to the next. 

“In my career, I’ve often not agreed with what the FDA has said, but I’ve at least relied on their consistency,” said Kirk, who’s worked in biotech for more than two decades. “That doesn’t appear to be what’s happening now. It feels more stochastic and maybe even capricious, what’s going on at the FDA. And this isn’t good for patients. It’s definitely not good for the biotech ecosystem as a whole.”

Continue to STAT+ to read the full story…

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StockWatch: Price War Dampens Lilly Surge After Oral GLP-1 Wins FDA Nod

Eli Lilly (NYSE: LLY) won the approval it sought when the FDA authorized the company’s oral obesity drug Foundayo™ (orforglipron), but the pharma giant’s post-approval stock bounce was short-lived.

Lilly shares rose 4% from $919.77 to $954.52 on the day of the announcement. But the momentum reversed into a 2% loss to $935.58 on Thursday, and for one important reason beyond simply the overall market decline triggered by investors losing confidence in a speedy end to the Iran war.

Investors (as reflected in analysts’ mixed observations) appeared divided on how quickly Lilly can generate sales this year for Foundayo, a small molecule glucagon-like peptide-1 (GLP-1) receptor agonist. That division results from the competition shaping up on the drug’s price with obesity arch-rival Novo Nordisk (shares traded on Nasdaq Copenhagen as NOVO-B; ADRs traded on NYSE as NVO).

Novo Nordisk got a jump on Lilly in the oral obesity drug front in December when the Danish biotech giant won FDA approval for oral Wegovy® (semaglutide), a once-daily 25 mg tablet indicated for chronic weight management. Analysts consider oral Wegovy sales to have started strong, with total prescriptions reaching 577,000 and 52,000 filled during the week ending March 20.

Lilly is expected to make Foundayo available directly to patients through its LillyDirect direct-to-consumer services and support platform starting Monday. There, a starting dose of 0.8 mg is being priced at $149/month, rising to $199/month for 2.5 mg, $299/month for the 5.5 mg and 9 mg doses, and up to $349/month for the highest doses of 14.5 mg and 17.2 mg. However, high-dose patients will automatically receive the $299/month price on their first purchases and keep it if they refill their prescription within 45 days of their previous prescription.

Patients paying through commercial insurance plans will be eligible for discounts that reduce Foundayo’s out-of-pocket cost to patients for 1-, 2-, or 3-month prescription fills to $5 a month.

“A positive surprise is that the approval was for a tablet formulation, which is less expensive to manufacture” than the capsule versions studied by Lilly during clinical trials, David Risinger, a senior managing director and senior research analyst covering diversified biopharmaceuticals at Leerink Partners, shared in a research note.

Lilly told Risinger that it conducted a bioequivalence study comparing capsules to tablets, which, according to the company, can be manufactured more efficiently than capsules and use less active pharmaceutical ingredient. The high dose studied in Lilly’s Phase III trials of orforglipron, 36 mg, corresponds to the highest capsule dose of 17.2 mg.

Price competition

Lilly has sought to price its oral obesity drug competitively with Novo Nordisk’s oral Wegovy, which starts at $149/month for the lowest dose of 1.5 mg, then rises to $199/month for the 4 mg dose, with new patients paying $149/month through August 31. Prices rise to $299/month for 9 mg and 25 mg doses.

However, patients who sign up for a 12-month subscription to oral Wegovy through Novo Nordisk’s telemedicine partner-providers enjoy a $50 discount that brings their monthly cost down to $249. And commercial insurance patients who agree to local pharmacy pickup with a savings offer can pay as little as $25/month, subject to a maximum savings of $100/month.

The price competition explains why buyers of securities for themselves or clients—the “buy side” in Wall Street jargon—have lowered their 2026 forecasts for Foundayo sales by more than half, from about $4 billion to less than $2 billion, Trung Huynh, an analyst with RBC Capital Markets, wrote in a research note. Huynh cited a consensus of analysts which is projecting approximately $1.6 billion in 2026 sales, though a Reuters spot check of investment brokerages found a range for this year’s projected sales of $1.5 billion to $2.8 billion.

“Although there have been headwinds on pricing erosion in the GLP-1 space, we believe there is substantial upside with the expected Medicare Part D expansion later this year,” Huynh added. The expansion of sales to the Medicare Part D program would cap patient copays at $50 per month.

Huynh and RBC Capital have projected Foundayo will reach peak-year sales of $36 billion—14% above the $31.68 billion racked up by last year’s best-selling prescription drug, the multi-indication cancer immunotherapy blockbuster Keytruda® (pembrolizumab) marketed by Merck & Co. (NYSE: MRK).

The highest peak sales forecast comes from Citi Research, where Geoff Meacham, PhD, the firm’s head of healthcare research and a managing director specializing in U.S. pharma and biotech research, has projected more than $40 billion. At the low end, a consensus of analysts surveyed by Bloomberg News expects Foundayo peak sales to reach $18 billion by 2030.

$50M upfront

Both ends are a far, far cry from the $50 million upfront that Lilly paid in 2018 to license orforglipron, then called OWL833, from Chugai Pharmaceutical, which discovered the drug and is owned by Roche Holding (SIX Swiss Exchange: ROP and RO; OTCQX: RHHBY). Lilly also agreed to pay Chugai up to $390 million in potential payments tied to achieving milestones.

At the time, OWL833 was deemed Phase I ready for clinical studies in type 2 diabetes—the indication for which Lilly markets its GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonist tirzepatide as Mounjaro®, and Novo Nordisk markets its GLP-1 receptor agonist semaglutide as Ozempic®.

“Overall, we continue to believe that injectable anti-obesity medications will retain the majority of market share (roughly 80%, based on our estimates) in the United States due to the high potency of injectables coupled with a more elevated U.S. BMI population,” Andy T. Hsieh, PhD, a partner and biotechnology analyst with William Blair, wrote in a research note.

Beyond competitive pricing and lower manufacturing costs, Lilly has emphasized a convenience advantage over oral Wegovy—starting with its public announcement of the approval, whose headline referred to Foundayo as “the only GLP-1 pill for weight loss that can be taken any time of day without food or water restrictions.”

While Foundayo can be taken morning, afternoon, or evening, oral Wegovy, by contrast, requires patients to take the pill with up to 4 ounces of water on an empty stomach as soon as they wake up, then fast for 30 minutes before they can eat or drink.

“Accordingly, we expect Foundayo to blunt the uptake of oral Wegovy upon its availability (starting on April 6), though oral Wegovy retains a pricing advantage,” Hsieh concluded.

Huynh of RBC Capital agreed, citing a survey by his firm of about 200 patients, payers, and prescribers: “Our recent survey indicated that Foundayo would be a preferred oral option amongst patients since it has no dosing restrictions.”

Not so, Novo Nordisk CEO Maziar (Mike) Doustdar told CNBC last month: “People are really interested because it’s the most efficacious pill right now in the market.”

Novo Nordisk cites efficacy

Novo Nordisk sought to reinforce that message via an announcement trumpeting that its 25 mg dose of oral Wegovy showed “significantly” greater mean weight loss than the 36 mg dose of Foundayo, according to a population-adjusted indirect treatment comparison using data from two clinical trials:

  • OASIS 4 (NCT05564117), a 307-patient randomized study which evaluated once-daily oral Wegovy 25 mg in overweight or obese adults with at least one self-reported unsuccessful dietary effort to lose body weight, to measure their percentage change in body weight and whether it was ≥5% at the end of treatment at week 64.
  • ATTAIN-1 (NCT05869903), a 72-week, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of orforglipron (6 mg, 12 mg, and 36 mg) as monotherapy vs. placebo in 3,127 adults with obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, OSA, or cardiovascular disease, who did not have diabetes.

Novo Nordisk plans to present details of its study, called ORION, at the Obesity Medicine Association’s annual Obesity Medicine 2026 conference, set for April 10-12 in San Diego.

News of the FDA approval for Foundayo caused Novo Nordisk shares to dip 0.1% Wednesday from DKK 231.15 ($35.65) to DKK 230.90 ($35.61). But the shares finished the trading week climbing nearly 3% Thursday to DKK 236.90 ($36.53).

U.S. and major European markets were closed on Friday in observance of Good Friday.

Foundayo is the fifth prescription drug to be authorized under the FDA’s Commissioner’s National Priority Voucher program, through which the agency awards vouchers to drug developers whose work will address a health crisis in the United States, deliver more innovative cures, address unmet public health needs, and increase domestic drug manufacturing as a national security issue.

The approval came nearly 10 months ahead of Foundayo’s target decision date of January 20, 2027, under the PDUFA (Prescription Drug User Fee Act) program, and just 50 days after Lilly filed a new drug application (NDA) for the oral obesity drug with the FDA.

Leaders and laggards

  • Inovio Pharmaceuticals (NASDAQ: INO) shares nosedived 35% from $1.74 to $1.13 Thursday after the developer of DNA therapies to treat and prevent HPV-related diseases, cancer, and infectious diseases announced that it priced at $1.40 a share an underwritten public offering of 12.5 million shares of common stock, plus accompanying Series A and Series B warrants, each series enabling potential purchase of up to 12.5 million shares (or pre-funded warrants in lieu thereof). The dilutive offering is projected to raise $17.5 million in gross proceeds—$16 million in net proceeds, rising to $18.4 million if underwriter Piper Sandler exercises in full its 30-day option to purchase up to 1.875 million additional shares and all Series A and Series B warrants (1.875 million shares each series). Net proceeds are intended to fund a potential commercial launch of INO-3107, a recurrent respiratory papillomatosis candidate under FDA review with a target decision date of October 30, as well as a confirmatory trial for INO-3107 if required, pipeline development, and general corporate purposes.
  • Oric Pharmaceuticals (NASDAQ: ORIC) shares tumbled 19% from $12.67 to $7.47 Wednesday after the cancer drug developer said it will advance rinzimetostat (ORIC-944) into a 600-patient Phase III trial (Himalaya-1 ) after generating positive data from its Phase Ib trial (NCT05413421) assessing rinzimetostat plus the Bayer (XETRA: BAYN)-marketed Nubeqa® (darolutamide) as a once-daily treatment for metastatic castration-resistant prostate cancer (mCRPC) in patients previously treated with abiraterone acetate (abiraterone). At a median follow-up of 4.9 months, the combination showed radiographic progression-free survival (rPFS) rates of 93% at 3 months, 84% at 4 months, and 84% at 5 months—rates consistent, Oric said, with the competitor PRC2 inhibitor currently in Phase III in post-abiraterone mCRPC patients and superior to available standard-of-care therapies showing rPFS rates of approximately 60% to 75%. Also, 47% of patients (7/15) achieved a PSA50 response, with 33% (5/15) confirmed, while 71% of patients (10/14) achieving >50% circulating tumor (ctDNA) reduction. Jefferies analyst Maury Raycroft, PhD, reported that some investors viewed rinzimetstat as “a better fit strategically” with Johnson & Johnson (NYSE: JNJ)-marketed Erleada® (apalutamide).
  • Sangamo Therapeutics (NASDAQ: SGMO) shares climbed 20% from 25 cents to 30 cents between Tuesday and Thursday after the genetic medicine developer said it expects to complete this summer its rolling Biologics License Application (BLA) submission seeking FDA approval for isaralgagene civaparvovec (ST-920), a gene therapy candidate being developed to treat Fabry disease, subject to securing adequate additional funding, while continuing business development discussions for a potential Fabry commercialization agreement. Sangamo said it is advancing the chemistry, manufacturing, and controls (CMC) module ahead of completion of the rolling BLA submission. Since launching its rolling BLA submission in December under an Accelerated Approval pathway, Sangamo has submitted preclinical and clinical modules, as well as submitted its antibody assay companion diagnostic, designed to screen patients for eligibility with isaralgagene civaparvovec, to the FDA’s Center for Devices and Radiological Health (CDRH), seeking Premarket Approval (PMA).

The post StockWatch: Price War Dampens Lilly Surge After Oral GLP-1 Wins FDA Nod appeared first on GEN – Genetic Engineering and Biotechnology News.

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Social cognitive deficits and altered multi-brain dynamics during problem-solving in heroin abstainers: An fNIRS hyperscanning study

Despite extensive research on the neurobiology of addiction, little is known about how repeated drug use and withdrawal are related to social functioning impairments in humans, a highly social species. This obscures the broader societal impact of drug addiction and limits treatment efficacy. This study examined social cognitive impairment and its multi-brain neural underpinnings during socially interactive problem-solving in heroin use disorder (HUD), and further explored their co-occurrence with protracted withdrawal symptoms.

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Low Birthweight Increases Risk of Early Stroke

Research led by the University of Gothenburg in Sweden suggests that low birthweight is a risk factor for having a stroke in younger adulthood.

In a study including just under 800,000 people, the investigators found that risk for early stroke events was 18-23% higher in men and women who had a birth weight under the median level than those with a higher birth weight.

Around 795,000 people in the U.S. have a stroke each year. Although it can affect people of any age, it is much more common in older individuals with estimates of prevalence suggesting that 0.9% of 18–44 year olds have strokes versus 3.8% of those in the 45–64 year age group and 7.7% of people aged 65 and over.

Low birth weight has been previously linked to an increased risk for stroke in several studies. Researchers think that low birth weight is an indicator of exposure to an adverse environment in the womb that may adversely affect the cardiovascular system of the fetus in a way that increases stroke risk—for example, by increasing the risk of high blood pressure.

Over the last 10-15 years, stroke prevalence has stayed the same in older adults but has gone up by 14-16% in 18-64 year-olds. Lina Lilja, a doctoral student at the University of Gothenburg, and colleagues aimed to investigate whether low birth weight increased the risk of stroke in younger adults.

They included 420,173 men and 348,758 women from Sweden who were born between 1973 and 1982 and followed up from birth until 2022. The researchers collected data on birth weight, gestational age, and body mass index in young adulthood, as well as information on first stroke and the type of stroke.

Overall, 2252 first stroke events were recorded at an average age of 36 years. Of these, 1624 were ischemic stroke (average age 37 years) and 588 were intracerebral hemorrhage (average age 33 years).

The results, which will be presented at the European Congress on Obesity in Istanbul later this year, showed that birth weight below the median (3.5kg) increased the risk for all stroke by 21%. The rates of stroke were slightly higher in men with a low birthweight at 23% versus women with a low birthweight at 18%.

Notably, gestational age at birth and young adult body mass index were not linked to stroke risk in this study.

The post Low Birthweight Increases Risk of Early Stroke appeared first on Inside Precision Medicine.

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Pancreatic Cancer Development Driven by NADPH Disruption

Researchers at the University of Michigan have uncovered metabolic pathways that explain how pancreatic cells transition from acinar-to-ductal metaplasia to pancreatic ductal adenocarcinoma (PDAC). The study, published in Nature Metabolism, detailed on how reduced production of a molecule central to biosynthesis and oxidative stress control called NADPH alters cellular conditions to favor cancer progression. By examining precancerous pancreatic lesions, the team found that disruptions in enzymes responsible for NADPH production increase oxidative stress, accelerating the formation of lesions and, in some cases, the progression to PDAC.

“We know a lot about how pancreatic tumors behave and look, but we don’t know how they become cancerous,” said lead author Megan Radyk, PhD, a former postdoc in the lab of Costas Lyssiotis, PhD, at the University of Michigan and now an assistant professor at Roswell Park Comprehensive Cancer Center. “We wanted to learn about what metabolic changes happen before you get an established tumor.”

PDAC is the most common form of pancreatic cancer and has a low five-year survival rate. The disease develops through a stepwise process that begins with acinar-to-ductal metaplasia (ADM), a reversible state in which pancreatic cells respond to injury or inflammation by adopting a duct-like phenotype. Under normal conditions, these cells can revert to their original state. However, in the presence of oncogenic KRAS mutations, this process is disrupted, leading to persistent ADM and progression to pancreatic intraepithelial neoplasia (PanIN), which can ultimately become PDAC.

NADPH’s normal role is in maintaining cellular homeostasis. It supports the synthesis of lipids, cholesterol, and nucleotides, and it aids antioxidant systems that regulate reactive oxygen species (ROS). Under normal conditions, NADPH helps neutralize ROS, preventing cellular damage. The current study, however, demonstrated that lower levels of NADPH impair antioxidant defenses, leading to increased ROS and lipid peroxidation, which in turn promote the formation of precancerous lesions.

The researchers identified two NADPH-producing enzymes for their work: glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme 1 (ME1). Both enzymes support the production of the appropriate levels of NADPH needed for biosynthesis and ROS regulation.

Using a multimodal approach involving RNA sequencing, metabolomics, and mouse models with oncogenic KRAS mutations, the Michigan team studied how the loss of these two enzymes affects pancreatic tissue. They observed that deficiency in either G6PD or ME1 increased ROS levels and accelerated the formation of ADM and pancreatic intraepithelial neoplasia (PanIN) lesions. Antioxidant treatments, including glutathione and N-acetyl cysteine, reduced lesion formation, further bolstering the current understanding of the role of oxidative stress in early tumorigenesis. The team achieved similar results when these methods were applied to human pancreatic tissue samples.

But results from later in the study showed that the two enzymes played distinct roles in the later stages of PDAC. While they both contributed to early lesion formation, only the loss of ME1 promoted progression to PDAC. This suggests that although both enzymes regulate NADPH and oxidative stress, they have distinct roles in later metabolic demands of cancer cells.

The study builds on prior research showing that KRAS mutations drive metabolic reprogramming and ROS production in pancreatic cells. Previous work has also indicated that antioxidant pathways, including those regulated by NRF2, are activated during tumor initiation.

Clinically, these findings suggest that targeting metabolic pathways involved in NADPH production could provide a strategy to intercept pancreatic cancer before it fully develops. Measuring levels of G6PD, ME1, or related metabolites could also serve as biomarkers to identify patients at higher risk of lesions progressing to cancer.

“Our study can help the search for new biomarkers that can intercept pancreatic cancer before it progresses,” the researchers wrote.

Future research will focus on identifying additional enzymes that regulate NADPH levels and determining how these pathways can be targeted safely. The researchers also plan to study whether patients with mutations in G6PD, ME1, or related pathways have an increased risk of pancreatic disease.

The post Pancreatic Cancer Development Driven by NADPH Disruption appeared first on Inside Precision Medicine.