Netanyahu: Israel to intensify attacks

 Israeli Prime Minister Benjamin Netanyahu announced on Tuesday that the country will intensify its armed campaigns against Hezbollah and Iran.

Commenting on Hezbollah's missile launches on northern Israel during a visit to the Palmachim Airbase, Netanyahu stressed that the organization "made a very big mistake when it attacked us." He accused it of dragging Lebanon into the conflict "solely because of the death of that mass murderer with whom they have no connection." "They need to look out for themselves, and they would do well to do so quickly. We will continue to do what is necessary for our defense," the prime minister pointed out.

Moreover, Netanyahu vowed that Israel "continue to strike Iran with force."

https://breakingthenews.net/Article/Netanyahu:-Israel-to-intensify-attacks/65791605

Trump may support armed militia in Iran

 United States President Donald Trump may be looking at the option of using an armed militia in Iran. The move would turn Iranian factions into ground forces, the Wall Street Journal reported on Tuesday, citing US officials.

While previous reports indicate he already held a telephone call with Kurdish leaders, the American head of state has not made a final decision on the matter, including whether he would provide arms, training, or intelligence to such groups, the media agency's sources confirmed.

Trump yesterday stated he does not rule out sending US ground troops into Iran.

https://breakingthenews.net/Article/Trump-may-support-armed-militia-in-Iran/65791371

After phase 3 clean sweep, Roche plans oral BTK filing in MS

 Roche's oral BTK inhibitor fenebrutinib has hit the spot in the final trial in its phase 3 programme, in relapsing multiple sclerosis (RMS), and is now being prepared for regulatory filings.

The FENhance 1 met its primary endpoint, showing that fenebrutinib reduced relapses by 51% compared to teriflunomide in RMS, which Roche said was "consistent" with the 59% reduction seen in its previously reported FENhance 2 trial.

In a statement, Roche said the two results equate to patients having approximately one relapse every 17 years, with accompanying reductions in the number of new brain lesions.

The two studies – along with recently reported FENtrepid in primary progressive multiple sclerosis (PPMS) – will now be submitted to regulatory authorities around the world, according to the Swiss pharma group.

"These pivotal results, together with the earlier data, provide convincing evidence that fenebrutinib can become the first high-efficacy oral treatment for RMS and PPMS," said Roche's chief medical officer, Levi Garraway.

Roche is in a race to become the leading oral BTK therapy for MS, with the broadest label, and it is fair to say that the class has had variable clinical success in recent years.

Fenebrutinib's closest rival is Sanofi's tolebrutinib, which was unable to show a statistically significant benefit in RMS in the GEMINI-1 and GEMINI-2 studies and PPMS in PERSEUS, but did hit the mark in the HERCULES trial involving patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS).

Tolebrutinib has been approved for nrSPMS in the United Arab Emirates (UAE), but in a setback for Sanofi was turned down by the FDA for nrSPMS last year, after a delayed review, over concerns that potential liver side effects (PDF) may not be managed by the company's proposed patient monitoring protocol.

Liver toxicity a concern?

Roche seems to have anticipated regulatory scrutiny of its proposed filings, and noted in its statement today that elevations in transaminase levels – a marker for liver damage – were "comparable" with teriflunomide.

However, there were eight fatalities in the FENhance studies, compared to one in the teriflunomide arm, which will no doubt catch the attention of regulators. The company added that these had various causes and occurred at different points in treatment in the fenebrutinib arms, and further analyses are ongoing to better understand the findings.

Tolebrutinib, meanwhile, remains under regulatory review in other jurisdictions, including Europe, and Sanofi was asked by the EMA to provide oral arguments at a meeting held at the end of January to support its EU application. A decision by the EMA's human medicines committee, the CHMP, is due this quarter.

https://pharmaphorum.com/news/after-phase-3-clean-sweep-roche-plans-oral-btk-filing-ms

'Dismal' survival demands change in bile duct cancer therapy

 An international group of cancer experts has called for fundamental change to healthcare approaches for bile duct cancer, which kills three-quarters of patients within a year of diagnosis.

The group of 147 opinion leaders, which includes Prof John Bridgewater of UCL Cancer Institute in the UK, is calling for rapid improvements in diagnosis, treatment, and research for this type of cancer, also known as cholangiocarcinoma (CCA), in a consensus statement published in Nature Reviews Gastroenterology & Hepatology.

CCA is a rare, but aggressive disease that usually develops and progresses silently, meaning most people are diagnosed at a late stage when treatment options are limited. Symptoms can include jaundice, abdominal pain, weight loss, pale stools, and itching, but are often mistaken for less serious conditions.

Despite several advancements in treatment over the past decade, the prognosis of patients with CCA continues to be dismal, with a five-year overall survival rate of less than 20%. Up to 90% of patients are diagnosed too late for surgery, which is currently the only potential cure, and the cancer kills around 3,000 people in England alone every year.

There is a desperate need for earlier diagnosis, through greater awareness of symptoms and faster referral pathways, along with wider access to specialist surgery and cancer centres, according to the experts from the European Network for the Study of Cholangiocarcinoma (ENSCCA).

They also call for routine molecular testing to match patients with available targeted treatments, such as drugs that address genetic alterations like IDH1/2 mutations, FGFR2 fusions, HER2, and BRAF V600E mutations, and increased funding for research and clinical trials of new therapies.

Molecular testing is critical because targeted drugs and immunotherapies such as checkpoint inhibitors can help patients live longer, but they can only be used if doctors know the cancer's specific genetic makeup.

"Bile duct cancer remains one of the hardest cancers to treat. Earlier diagnosis, better access to specialist care, and routine molecular testing could dramatically improve survival," said Prof Bridgewater, who also noted that the incidence of CCA has been steadily rising, including among younger adults, placing growing pressure on NHS cancer services.

"Too many UK patients are diagnosed when it is already too late," he added. "Faster diagnosis and fair access to advanced testing and treatments must become national priorities."

The UK's recently revealed National Cancer Plan does not include a specific target for CCA, but does include measures for rare and less common cancers and an objective for England to be in the top 25% of 28 countries in terms of survival for these diseases by 2035.

https://pharmaphorum.com/news/dismal-survival-demands-change-bile-duct-cancer-therapy

CMS extends deadline for MFN pricing pilot scheme

 The Centers for Medicare & Medicaid Services (CMS) in the US has extended the deadline for companies to take part in its GENEROUS pilot programme, designed to implement Most-Favoured Nation (MFN) pricing for outpatient drugs reimbursed by Medicaid.

The agency has pushed back the deadline for participation in the scheme from the end of this month to 30th April, leading to speculation that it may be struggling to find companies willing to take part.

In an update, CMS said the extension will "provide interested drug manufacturers more opportunity to join the model," adding that it will hold meetings with interested manufacturers from the start of April and plans to hold a town hall meeting to discuss the operational and methodological details of the model later this spring.

However, the final deadline for participation will remain unchanged at 30th June, according to the CMS, which is seeking small- and mid-sized company volunteers.

First announced last November, GENEROUS (GENErating cost Reductions fOr US Medicaid) is a voluntary scheme that invites pharma companies to negotiate standardised coverage criteria for each of their products with Medicaid, avoiding the need to negotiate access deals in every state separately.

In simple terms, drugmakers will get uniform coverage across all participating Medicaid programmes in return for setting the prices of medicines provided by Medicaid in the US to the lowest charged for them in eight reference countries, specifically the UK, France, Germany, Italy, Canada, Japan, Denmark, and Switzerland.

"Based on feedback from drug manufacturers, CMS has decided to give interested companies additional time to apply for the GENEROUS Model," commented CMS Administrator Mehmet Oz.

"We are committed to partnering with states and manufacturers to drive down drug prices and ensure that the most vulnerable Americans have access to life-saving medications."

Since GENEROUS was first announced, commentators have expressed concern that the pricing model could discourage some manufacturers from offering certain drugs through Medicaid, which provides health insurance for Americans with limited income and resources.

A letter (PDF) written by more than 150 economists to HHS last year said that MFN policies – which are also being applied to Medicare by the Trump administration – risk reducing patient access to medicines, cutting investment in industry R&D, and cost-shifting that raises the prices of other medicines.

Centre-right political think-tank, the American Action Forum, argued in a recently-published analysis that participating in GENEROUS would be a "poor business decision" for drugmakers, saying it is unclear "how these rebates would compare to payments already in place and if this new approach will undermine preferred drug lists."

CMS has pointed out that the cost of Medicaid spending on prescriptions in 2024 – at $100 billion, or $60 billion after manufacturer rebates – was a $10 billion increase on the prior year and underscores the "urgency for reform."

https://pharmaphorum.com/news/cms-extends-deadline-mfn-pricing-pilot-scheme

Ascendis Enters Achondroplasia Arena as FDA Approves First Weekly Drug

 

Yuviwel will compete with BioMarin’s Voxzogo. Meanwhile, BridgeBio is working to bring its own achondroplasia drug, the FGFR3 blocker infigratinib, to the market.

The FDA has given the go-ahead to Ascendis Pharma’s navepegritide to boost growth in kids 2 years and older with achondroplasia. The drug will be marketed under the brand name Yuviwel.

Yuviwel is the first drug on the market to use weekly dosing to provide sustained systemic exposure to C-type natriuretic peptide (CNP), a key signaling molecule affected in achondroplasia, according to Ascendis’ Friday news release. Yuviwel will be available to patients through prescribing physicians in the “early part of the second quarter,” the biotech said.

Achondroplasia is a genetic disease characterized by faulty bone development in children. Though classified as a rare disease, achondroplasia is the most common cause of dwarfism. Navepegritide, Yuviwel’s active ingredient, addresses a key disease pathway by providing continuous exposure to CNP, thus promoting bone growth.

Pivotal findings from the Phase 2b APPROACH study showed that annualized growth velocity increased by 1.49 cm/year in patients on Yuviwel versus placebo—a treatment effect that was statistically significant—as per data published in JAMA Pediatrics in November 2025. Yuviwel’s edge over placebo started 12 weeks after treatment initiation and persisted throughout the study.

Yuviwel also improved the ratio in children’s upper-to-lower body segments, indicating more proportional bone growth.

Alongside Friday’s approval, Ascendis also received a rare pediatric disease priority review voucher from the FDA, which it can use to secure an expedited review of a drug that would have otherwise gone through the agency’s standard timeline. The biotech also has the option to sell this voucher, which could go for hundreds of millions of dollars.

Yuviwel could “transform the treatment of achondroplasia,” Ascendis CEO Jan Mikkelsen said in a statement.

Currently, the only other available treatment for achondroplasia is BioMarin’s Voxzogo, which similarly targets the CNP disease pathway but is injected daily, as opposed to Yuviwel’s weekly schedule. The drug was approved in November 2021 and seems to be waning in popularity. During the company’s third-quarter 2025 earnings call, BioMarin walked back its previous goal of hitting $4 billion revenue by 2027, a decision that CEO Alexander Hardy said at the time was heavily influenced by incoming competition to Voxzogo.

Besides the two marketed therapies from Ascendis and BioMarin, other companies are advancing their own achondroplasia therapies. These include BridgeBio and its FGFR3 blocker infigratinib, which is currently in late-stage development. Data from the Phase 3 PROPEL 3 study, released last month, showed an annualized height velocity improvement of 2.10 cm/year versus placebo. A new drug application is slated for the second half of 2026.

https://www.biospace.com/fda/ascendis-enters-achondroplasia-arena-as-fda-approves-first-weekly-drug

Boehringer Ingelheim Axes MASH Pact With OSE After Disappointing Mid-Stage Data

 

OSE Immunotherapeutics has kicked off a strategic realignment initiative that involves deprioritizing the AbbVie-partnered OSE-230 and focusing its resources on the late-stage development of its ulcerative colitis candidate lusvertikimab.

Boehringer Ingelheim is abandoning its metabolic dysfunction-associated steatohepatitis program with OSE Immunotherapeutics after a mid-stage study fell short of its primary endpoint.

Specifically, results from an exploratory Phase 2 study “did not demonstrate efficacy to support further development in this indication,” OSE said in a Monday release. The French biotech did not reveal specific data from this trial.

OSE and Boehringer first partnered up in April 2018. The German pharma at the time paid €15 million ($17.5 million) upfront and promised an additional €15 million ($17.5 million) in near-term commitments and up to €1.1 billion ($1.28 billion) in development, commercialization and sales milestones. In May 2024, the companies deepened their engagement. The MASH candidate, called BI 770371, was part of this expanded agreement.

It is unclear if the alliance will remain, but on its website, OSE lists BI 770371 as its only Boehringer Ingelheim–partnered asset.

The discontinuation of the MASH program does not affect BI 770371’s development in cancer, for which the molecule has a distinct mechanism of action, OSE said. There are “multiple” early-stage oncology studies running, which are “progressing as planned.”

Boehringer’s pullback on Monday seems to have triggered a strategic restructuring initiative. OSE is suspending the development of its investigational antibody OSE-230, which it was proposing for chronic and severe inflammation, in order to funnel more of its resources into “late-stage, high-potential assets,” the company said.

In particular, OSE will concentrate on advancing the CD127 blocker lusvertikimab, which recently wrapped up Phase 2 development for moderate to active ulcerative colitis. According to a strategic roadmap released Monday, OSE is currently working on a subcutaneous formulation of lusvertikimab, which it expects to be ready by the first half of 2027. A Phase 2b/3 trial in ulcerative colitis could start later that same year.

OSE will also develop lusvertikimab for chronic pouchitis and hidradenitis suppurativa, with initial Phase 2 data expected in 2028.

OSE-230, the deprioritized asset, is partnered with AbbVie and has also been a source of headache for the biotech.

AbbVie and OSE first partnered in February 2025, with the pharma paying $48 million upfront for the exclusive right to advance and commercialize the asset. In December 2025, however, AbbVie amended the agreement and asked OSE to assume responsibility over preclinical and Phase 1 development.

While AbbVie still retains the right to take charge of future clinical studies, OSE will now have to shoulder ABBV-230’s early-stage development.

https://www.biospace.com/business/boehringer-ingelheim-axes-mash-pact-with-ose-after-disappointing-mid-stage-data