FDA backs first AI tool for use in trials, targeting MASH

 The FDA has qualified the first AI-based tool that can be used in clinical trials involving patients with metabolic dysfunction-associated steatohepatitis (MASH) to help measure disease activity.

Called AIM-NASH, it is a cloud-based tool designed to help pathologists score liver biopsy components on measures such as fat infiltration (steatosis), inflammation (hepatocellular ballooning and lobular inflammation), and scarring (fibrosis), which are all features of MASH.

FDA qualification means it can now be used in any drug development programme for a MASH treatment and support regulatory filings of new therapies. As it stands, there are two drugs approved for MASH – Madrigal Pharma's THR β-selective agonist Rezdiffra (resmetirom) and Novo Nordisk's GLP-1 agonist Wegovy (semaglutide) – and dozens more coming through the pipeline.

It has been billed as pharma's next big growth area, with some analysts predicting a market potentially worth tens of billions of dollars a year.

Metabolic dysfunction-associated steatotic liver disease (MASLD), including its more severe form MASH, is the most common chronic liver disease in the world, affecting roughly 38% of the world's adult population and claiming hundreds of thousands of lives every year. The condition is largely associated with obesity and an unhealthy diet and lifestyle, and is on the rise in industrialised nations.

In MASH, the disease has progressed to include advanced, life-threatening complications like cirrhosis, worsening of liver function that can require a transplant, and liver cancer.

AIM-NASH, developed by Boston-based AI specialist PathAI, is designed to reduce the burden of scoring biopsy samples, which is currently carried out by multiple independent experts and is time-consuming and can also be prone to variable results.

It uses AI algorithms to analyse images of liver biopsies and provides scores according to the standard NASH Clinical Research Network scoring system, according to the FDA. The EU drugs regulator, the EMA, endorsed use of the tool in MASH trials earlier this year.

The agency stressed that the process "keeps humans involved, as pathologists are fully responsible for final interpretation, reviewing the whole slide image and AIM-NASH outputs before accepting or rejecting the AI-generated scores."

There has been a major push to adopt digital and AI technologies by the FDA under the Trump administration, with other recent moves including the launch of a real-world review process to make it easier to bring digital health technologies (DHTs) to market, an agentic AI platform that can be used by staff to automate complex tasks, and a generative AI (GenAI) system called Elsa designed to speed up review processes.

https://pharmaphorum.com/news/fda-backs-first-ai-tool-use-trials-targeting-mash

Assembly’s Antivirals Show ‘Striking’ Drop in Lesions, Viral Shedding in Early Genital Herpes Study

 

A mid-stage study for ABI-5366 will begin mid next year, while Assembly continues to assess the Phase II potential of ABI-1179.

Two of Assembly Biosciences’ investigational long-acting therapies showed strong antiviral activity in Phase I studies in recurrent genital herpes, opening the company’s path to mid-stage development.

Analysts at Guggenheim Partners, in a Monday note to investors, called the California biotech’s data “striking,” adding that the readout “strongly reinforces the greater efficacy potential of [Assembly’s] more potent, next-gen oral helicase-primase inhibitors.”

On Monday, Assembly released interim results from two Phase I studies of its oral herpes drug candidates, the weekly ABI-1179 and the monthly ABI-5366. Both trials were randomized and placebo-controlled, and enrolled patients positive for herpes simplex virus 2 (HSV-2) infection with recurrent genital herpes.

In its study, a 50-mg dose of ABI-1179 lowered viral shedding by 98% versus placebo over a 29-day observation period, which exceeds Assembly’s previous target of 80% to 85% shedding reduction, according to the company’s announcement. ABI-1179 also lowered genital lesion rates by 91% compared to placebo.

Meanwhile, the trial for ABI-5366 showed that drug cut viral shedding by 76% over 29 days, accompanied by an 88% decrease in confirmed genital lesions. The number of samples with high viral load, a potential surrogate indicator for HSV-2 transmission, was 81% lower in those on Assembly’s drug compared to placebo.

In a follow-up note on Monday evening, sent after a call with Assembly management, Guggenheim analysts reiterated that in ABI-1179 and ABI-5366, the biotech “has two strong candidates with both differentiated efficacy and more favorable dosing vs. standard of care.” The former, in particular, could unlock a “potential blockbuster novel weekly treatment opportunity” for the company.

Moving forward, Assembly plans to push both assets into mid-stage development. ABI-5366 is expected to start Phase II trials by mid-2026, according to a Mizuho Securities note on Monday, while the company continues to assess the Phase II potential of ABI-1179.

ABI-5366 and ABII-1179 work by targeting a key viral enzyme complex involved in HSV-2 replication. Disrupting this crucial viral function, Assembly claims on its website, can lead to “superior efficacy” than the current nucleoside analogs used for herpes treatment.

ABI-1179 came to Assembly from Gilead under an October 2023 partnership, according to the biotech’s Monday release. The pharma at the time fronted $100 million to collaborate with the biotech on its infectious disease assets, giving Gilead the ability to gain exclusive rights over Assembly’s pipeline programs.

https://www.biospace.com/drug-development/assemblys-antivirals-show-striking-drop-in-lesions-viral-shedding-in-early-genital-herpes-study

Terns ‘Unprecedented’ Leukemia Data Beats Novartis’ Scemblix

 

TERN-701 more than doubled the response rate of Novartis’ rival approved therapy in an early-stage trial, sending the biotech’s shares flying.

Terns Pharmaceuticals shares soared after chronic myeloid leukemia therapy TERN-701 doubled the response rate of Novartis’ approved STAMP inhibitor Scemblix in an early-stage trial.

“Unprecedented remains the only suitable adjective to describe the compound’s clinical profile,” William Blair analysts wrote Tuesday morning. Terns’ shares climbed 10% to $44.45 as the markets opened Tuesday—but pre-market trading saw the stock rise as high as 55% over the weekend in anticipation of Monday’s readout.

The results for TERN-701, revealed at the American Society of Hematology (ASH) annual meeting on Monday afternoon, showed a double whammy of improvement over Novartis’ offering. The Phase I CARDINAL trial featured patients with previously treated CML, with the readout including 38 efficacy-evaluable participants.

Terns’ allosteric BCR/ABL1 inhibitor achieved an overall major molecular response (MMR) rate of 75% at week 24, while 64% of patients achieved the MMR. The data also supported daily dosing and had no food effect.

“It is rare for an investigational agent to demonstrate unequivocal improvement in both clinical efficacy and safety and concurrently provide patients with better convenience of daily dosing with no food effect,” analysts at William Blair wrote in a note Tuesday. “We believe TERN-701 is on track to challenge Scemblix’s dominance and disrupt the treatment paradigm of CML.”

For comparison, Scemblix and another investigational CML asset, Enliven’s ELVN-001, had response achievement rates in the range of 24%-32% in their own trials, the firm wrote. The William Blair analysts wondered, therefore, will the “differentiated data turn into a Big Pharma bidding war?”

TERN-701 also “demonstrated the ability to salvage those who had previously been treated with Scemblix,” and relapsed, according to William Blair. An analysis of a small group of 10 patients who had previously received Scemblix showed a 43% MMR after treatment with Terns’ drug.

Analysts at BMO Capital Markets, in their own note on Monday, said the 75% MMR rate is impressive, but key to TERN-701’s commercial success is the ability to maintain that response. The CARDINAL data showed just that, with patients switching to the drug showing stronger responses than they had previously achieved on other treatments.

BMO projected TERN-701 could bring in peak sales of $3.4 billion in the long term. Patients with CML typically take a drug for several years before switching to another to kick-start a response again. With TERN-701 exhibiting such strong response rates, BMO is confident in the revised peak sales target.

“CML often exhibits treatment switches, and active treatment commonly utilizes long, multi-year durations for therapy in between switches.

The readout represents a comeback story for Terns, which was previously focused on metabolic diseases, including assets in obesity and metabolic dysfunction-associated steatohepatitis (MASH). The biotech changed focus to TERN-701 earlier this year, citing an oversaturated market in obesity.

As for next steps, Terns will release more data from the CARDINAL trial next year and meet with regulators to develop a registrational trial in front-line and second-line CML. Executives told investors during a call Monday afternoon that the ASH abstract had galvanized patients and enrollment had “substantially improved.”

“With enrollment timelines likely becoming more impactful in 2026, we see this expedited timeline as a meaningful positive that could benefit development timelines in the coming year,” BMO wrote.

MMR typically translates well from Phase I to Phase III, according to William Blair’s analysts. “We are optimistic that the best-in-disease results will likely be replicated in the pivotal setting,” the firm said of the future clinical programs for TERN-701.

Terns immediately used the positive data to raise some cash, offering $400 million worth of shares in a public offering on Tuesday. The cash will be used to fund development of TERN-701, including launch preparations.

https://www.biospace.com/drug-development/terns-climbs-10-as-unprecedented-leukemia-data-beats-novartis-scemblix

CAR-T Developers Will Need Randomized Trials as FDA Eyes Tighter Approval Requirements

 

For traditional approval, CAR T therapies will need to establish superiority over current standard treatments, including already-approved CAR T products.

The FDA is eyeing regulatory changes that could make it harder for companies developing CAR T therapies to secure approvals for their products.

In a Perspective piece published Monday in the the Journal of the American Medical Association, Vinay Prasad, director of the agency’s Center for Biologics Evaluation and Research, along with three co-authors at the FDA, noted that while the FDA is adjusting its processes to “exercise regulatory flexibilities, when necessary,” it also needs to “maintain the high evidentiary standards for approval.”

In the future, Prasad wrote, assessing CAR T products though randomized controlled trials will be the FDA’s “preferred approach,” according to reporting from FirstWord Pharma, noting that the agency will be looking at the candidate’s effects on patient survival or on the time to the development of a particular event.

In addition, companies should also test their experimental CAR T therapies against existing standard treatments, including other CAR T products on the market, Prasad wrote in the JAMA piece. Single-arm trials with no controls will no longer be enough to support a CAR T approval. All seven CAR T therapies on the market were approved based on such studies.

Still, Prasad noted that durable treatment response findings from these one-arm studies can be used for accelerated approvals, but sponsors will still need to establish clinical benefit in a randomized and controlled trial for full approval.

These new CAR T guidelines add to the already-burdened cell therapy space, which in recent months has seen several high-profile exits and discontinuations. In CAR T, specifically, Regeneron in October canned the early-stage bbT369, which it obtained in January 2024 from 2seventybio, in what a spokesperson said was a “strategic business decision.” The asset was being tested in relapsed or refractory B-cell non-Hodgkin’s lymphoma. In March, CAR T specialist Cargo Therapeutics fired 90% of its staff and stopped all development work after its lead asset failed a Phase II study in January.

Two players that Prasad’s new CAR T guidelines could affect are Gilead and Arcellx, which are working together on the anti-BCMA therapy anitocabtagene autoleucel (anito-cel). The partners are running the registrational Phase II iMMagine-1 study, which does not include a control arm.

At this year’s annual conference of the American Society of Hematology, Gilead and Arcellx touted a 96% overall response rate for anito-cel, including a 74% complete response/stringent complete response rate. BMO Capital Markets on Sunday said these findings open a “clear path to a potential 2026 approval/launch.” It remains unclear how the FDA’s new CAR T rules will affect anito-cel’s regulatory timeline and prospects.

https://www.biospace.com/fda/car-t-developers-will-need-randomized-trials-as-fda-eyes-tighter-approval-requirements

https://breakingthenews.net/Article/Novo-Nordisk-buys-Akero-Therapeutics-in-dollar5.2B-deal/65322299

https://www.zerohedge.com/political/time-ukraine-have-elections-its-not-democracy-anymore-trump

Mexico to Hike China Tariffs, Raising Hopes of US Steel Relief

 

Mexico’s Congress is set to vote this week on President Claudia Sheinbaum’s proposed tariffs on China, part of a broader plan to shield local producers and ease trade tensions with the US. The move is fueling expectations that it could soon make room for US tariff relief on Mexican steel and aluminum.

The bill, which imposes tariffs of up to 50% on imports from Asia, and China in particular, began being debated by a lower-house commission on Monday. Lawmakers aim to hold votes on the floors of both the House and the Senate before Dec. 15, when Congress enters its year-end recess.

https://www.bloomberg.com/news/articles/2025-12-08/mexico-to-hike-china-tariffs-raising-hopes-of-us-steel-relief