Data readout puts J&J's bladder cancer drug back on track

 Johnson & Johnson's confidence in its bladder cancer therapy TAR-200 – dented by a negative phase 3 readout last year – seems to be justified.

New data from the SunRISe-1 study of TAR-200 in patients with high-risk, non-muscle-invasive bladder cancer (HR-NMIBC) that has not responded to standard BCG treatment build the case for the drug as it heads towards an FDA decision on a marketing application in NMIBC later this year.

At the American Urological Association (AUA) that starts later this week, J&J is scheduled to report that TAR-200 achieved a 12-month duration of response in this form of bladder cancer, allowing patients with the highly recurrent disease to remain cancer-free for a longer period.

Moreover, it will also present what it says is "compelling" data from a new SunRISe-1 cohort involving patients with BCG-unresponsive, papillary-only HR-NMIBC, a group who are typically elderly and with significant co-morbidities.

Surgical removal of the bladder is the standard treatment option for this form of the disease, which can be challenging in this group, so an alternative that can delay the need for such an invasive procedure would be a major step forward for patients.

TAR-200 takes the form of a silicon-based drug delivery device that allows for the continuous release of medication – in this case the chemotherapy agent gemcitabine – directly into the bladder. It is inserted by a healthcare professional in a brief outpatient procedure, without the need for anaesthesia.

Last October, J&J reported disappointing results from the SunRISe-2 study of TAR-200, which involved people with muscle-invasive bladder cancer (MIBC) who were not receiving surgery to remove the bladder (cystectomy) and nearby lymph nodes. In that trial, the drug showed no improvement over the standard chemoradiation treatment.

At the time, the company said the readout was disappointing, but had no bearing on its projections of a $5 billion-plus peak sales potential for TAR-200 and other drugs based on the delivery technology, acquired when it bought Taris in 2019.

At AUA, there will also be a presentation on the phase 3 MoonRISe-1 trial of TAR-210, an intravesical formulation of J&J's FGFR kinase inhibitor Balversa (erdafitinib), which is being run in intermediate-risk NMIBC.

"Patients deserve more than the currently available treatment options," said Biljana Naumovic, US president, oncology, solid tumours, at J&J. "This innovation provides a bladder-sparing treatment option that can meaningfully improve outcomes while integrating seamlessly into any urology practice."

https://pharmaphorum.com/news/data-readout-puts-jjs-bladder-cancer-drug-back-track

Pfizer Mounts Defense of Cardiac Blockbuster as Alnylam, BridgeBio Enter Market

 

Alnylam and BridgeBio are competing for people who are switching from Pfizer’s blockbuster ATTR amyloidosis drug tafamidis while all three companies are fighting for new patients.

A three-way tussle has emerged in the growing ATTR amyloidosis market as Alnylam and BridgeBio Pharma have secured FDA approvals to challenge Pfizer.

Tafamidis, which Pfizer sells as Vyndaqel, Vyndamax and Vynmac, had the ATTR amyloidosis with cardiomyopathy (ATTR-CM) market to itself for five years. But BridgeBio won approval for Attruby, a drug with the same mechanism of action as tafamidis, in November 2024. Then the oral transthyretin stabilizers were joined on the market by the first silencer, Alnylam’s Amvuttra, in March. Amvuttra was already approved in ATTR with polyneuropathy (ATTR-PN).

ATTR-CM causes stiffening of cardiac muscle and heart failure, leading to death in around 2.5 years if left untreated. Cardiac capacity cannot be regained once lost. BridgeBio estimates there are around 240,000 ATTR-CM patients in the U.S. and BMO Capital Markets analyst Kostas Biliouris said he believes the market is big enough to accommodate multiple assets. Even so, competition is inevitable and the stakes are high.

Pfizer Bullish as Rivals Arrive

Pfizer reported $5.4 billion in sales for tafamidis in 2024, up more than 60% year on year. Matt Outten, chief commercial officer at BridgeBio, said at a Leerink investor event in March that around 24,000 people are on tafamidis. And about 30% to 40% of patients on tafamidis “are probably progressing” while a further 2,000 to 3,000 people are being newly diagnosed each quarter, he added.

Alnylam and BridgeBio are now competing for people who are switching from tafamidis. Pfizer CFO David Denton acknowledged the effect of the new entrants on a call with analysts to discuss 2025 guidance, saying that “Vyndaqel’s growth will be tempered primarily due to the unfavorable impact of the IRA and new competition in the U.S.”

Pfizer CEO Albert Bourla provided a detailed look at how the company expects the market to evolve at a TD Cowen event in March. The chief executive is confident Pfizer can keep current users, arguing that physicians “will never switch a patient to something different” when a medicine is working well. He is equally bullish on the company’s ability to compete for first-line users.

Bourla said that Pfizer “will maintain a lion’s market share” for new prescriptions “because of the network, the understanding of physicians of the brand.” Asked if he expects Pfizer to dominate new prescriptions, Bourla said “correct,” adding that the company will be “super dominant on the current prescriptions.”

Alnylam Targets First-Line Market

Alnylam has other ideas. On a conference call with analysts to discuss the FDA approval, Alnylam CEO Yvonne Greenstreet said Amvuttra has the potential to become the new standard of care. Tolga Tanguler, chief commercial officer at the company, used the call to make the case that ATTR-CM patients, knowing cardiac function cannot be regained, will want to get the injectable Amvuttra as a first-line therapy.

The biotech is forecasting sales of Amvuttra and Onpattro, the company’s other approved ATTR-PN drug, will rise to between $1.6 billion and $1.725 billion this year, a 36% increase at the midpoint of the range. Last year, when Alnylam only had approvals in ATTR-PN, the franchise grew 34%.

Alnylam is charging a premium for Amvuttra. The annual wholesale acquisition cost for Pfizer’s tafamidis is $268,000. BridgeBio priced Attruby at $244,500 a year. Alnylam set Amvuttra’s list price at an annual cost of $476,000. Tanguler said Alnylam will cut the net price of Amvuttra “via rebates and value-based agreements” as prescription uptake increases.

The Inflation Reduction Act could also impact what patients pay for Amvuttra. The law capped Medicare Part D out-of-pocket spending at $2,000. A patient who has already hit the cap, because they are on other medications, will pay nothing to take tafamidis or Attruby. Amvuttra is a Medicare Part B drug. These services have a 20% coinsurance. Medicare Advantage caps the annual cost at $9,350.

Amvuttra has confirmed coverage for virtually all insured ATTR-PN patients, Tanguler said, and Alnylam expects similarly broad coverage in ATTR-CM. The biotech is talking to U.S. payers and expects ATTR-CM sales to start ramping up in the second half of 2025. Alnylam is taking other steps to ensure patients can access Amvuttra, with a focus on the 170 health systems where 80% of ATTR-CM patients are treated.

Alnylam has been optimizing access pathways at those health systems to ensure people can receive the drug “at a convenient location, whether that’s an office, at an infusion center or, in some cases, in the patient’s home,” Tanguler said. The biotech had nearly 2,000 alternate sites of care as of March 20, Tanguler said, and was close to its goal of establishing treatment sites within 10 miles of 90% of patients.

BridgeBio Builds Launch Momentum

Alnylam is presenting Amvuttra’s quarterly subcutaneous dosing as a strength. BridgeBio pushed back against that idea. Outten said some ATTR-CM patients cannot drive or prefer not to. Family members might need to take hours out of their days to drive patients, who are often seniors, for injections, Outten said.

While Alnylam’s roll out of alternate sites of care could bring down geographic barriers to Amvuttra use, Outten expects some patients to prefer oral treatments. ATTR-CM patients already take pills multiple times a day for conditions such as high blood pressure, Outten said, so adding another drug has little effect on their routines.

Data on BridgeBio’s Attruby launch predate the approval of Amvuttra. The first two months of the launch exceeded expectations, BMO’s Biliouris said, with around 500 HCPs writing prescriptions for more than 1,000 patients. Biliouris predicted BridgeBio will generate first-quarter sales of $7 million to $14 million, beating the $5 million to $6 million consensus analyst forecast.

The competitive landscape looks likely to change in the coming years. Pfizer’s tafamidis is set to lose patent protection in the U.S. in 2028, allowing cheaper generic copies to come to market. Tanguler said the availability of generics might make combination therapy viable. In an April 4 note to investors, Mizuho analysts said that Pfizer’s work on a tafamidis tablet, which is in Phase I, could result in a formulation with patent protection through 2043.

The Mizuho team cited Pfizer’s investment in the tablet formulation as evidence the ATTR-CM market “is likely to be more durable beyond 2028.” With Alnylam, BridgeBio and Pfizer all betting on the opportunity, and generic companies waiting in the wings, the stage is set for intense competition and blockbuster sales.

https://www.biospace.com/business/pfizer-mounts-defense-of-cardiac-blockbuster-as-alnylam-bridgebio-enter-market

Trump admin to go after pensions, wages and tax returns to claw back student loan debt

 The Trump administration announced Tuesday that it would seize wages and go after the pensions of those who refuse to repay federal student loans they defaulted on.

“The government can and will collect default in federal student loan debt by withholding money from borrowers, tax refunds, federal pensions and even their wages,” White House press secretary Karoline Leavitt told reporters in her weekly briefing.

The Education Department had announced a day earlier it would be pursuing wages and tax refunds, but did not specifically state federal pensions would also be included.

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Karoline Leavitt said the Trump administration would be going after pensions, tax refunds and wages.Getty Images

The White House will restart the federal government’s “involuntary” collection program — that was paused under former President Joe Biden — on May 5.

The number of individuals defaulting on their student loans could reach 10 million in a few months, the Education Department said in a statement on Monday — accounting for 25% of federal loan portfolios.

All borrowers who have defaulted on their loans will receive a notice in two weeks informing them of the upcoming collection process.

“American taxpayers will no longer be forced to serve as collateral for irresponsible student loan policies,” Secretary of Education Linda McMahon said in a statement.

“The Biden Administration misled borrowers: the executive branch does not have the constitutional authority to wipe debt away, nor do the loan balances simply disappear.

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Student Debt relief advocates stand outside of the Supreme Court of the United States as they wait for the Supreme Court to release their opinion on whether or not to strike down President Biden’s student debt relief program.Getty Images for We, The 45 Mill

“Hundreds of billions have already been transferred to taxpayers. Going forward, the Department of Education, in conjunction with the Department of Treasury, will shepherd the student loan program responsibly and according to the law, which means helping borrowers return to repayment — both for the sake of their own financial health and our nation’s economic outlook.” 

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$1.6T in student debt is owed by federal borrowers.Allison Bailey/NurPhoto/Shutterstock

A loan is considered in default if the borrower misses payment for 270 days, or about 9 months.

Under the Treasury Offset Program, the government has the right to withhold 100% of defaulted borrowers’ tax returns, 15% of federal salary and 15% of Social Security.

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White House press secretary Karoline Leavitt takes a question during a press briefing at the White House in Washington, D.C., April 22, 2025.AP

Federal loan borrowers currently owe over $1.6 trillion in student debt.

The Trump administration has long said taxpayers should not be responsible for paying off other people’s loans — in response to the Biden administration’s proposal to forgive $400 billion in student loans.

“We must get our fiscal house in order and restore common sense to our countries. If you take out a loan, you have to pay it back — very simple,” Leavitt said.

https://nypost.com/2025/04/22/us-news/white-house-to-go-after-pensions-wages-and-tax-returns-to-claw-back-student-loan-debt/

What people who smoke a lot of weed have in common with psychosis patients: study

 What a buzzkill.

Smoking weed can certainly have an impact on your brain — and not just the potential for some serious paranoia.

Research published last week found that ER visits for cannabis use by people over the age of 65 has skyrocketed, and those seniors who need acute care for partaking are up to 72% more likely to develop dementia.

Now a new study published in JAMA Psychiatry has pinpointed another startling change to stoners’ brains.

There is growing evidence linking cannabis use and psychosis.Getty Images

The study revealed that people with cannabis use disorder — that is, using weed enough that it causes problems and impairs your life — have altered dopamine activity in the brain that closely resembles patterns observed in psychosis.

Using MRIs, researchers found increased dopamine-related signals in the midbrain regions among heavy cannabis users.

This area is crucial for motivation and reward processing and has been previously linked to psychotic symptoms such as hallucinations and delusions.

The more you use — the bigger the problem

The study focused on people aged 18 to 35. The heavy cannabis users had significantly higher neuromelanin-MRI signals — which measure function of dopamine, the happy hormone — in specific brain regions associated with psychosis severity.

This increase was most pronounced among people with more severe cannabis use disorder, indicating a dose-related pattern.

It’s not the first time smoking weed has been linked to a higher risk of psychosis.

For instance, a 2024 study found that frequent use of high-potency pot increased the likelihood of psychosis, independent of genetic predisposition.

“We hope this research helps inform young people about the potential risks associated with harmful cannabis use — especially those with a family history of psychosis or other factors that may increase their vulnerability,” lead author Jessica Ahrens, a PhD student in the Integrated Program in Neuroscience at McGill University, told PsyPost.

Previous research has suggested a link between heavy cannabis use and an elevated risk of psychosis.Getty Images
Losing touch with reality?

An unexpected finding was that those who did have cannabis use disorder did not report more personal issues due to their weed dependency — despite meeting all of the criteria for the condition.

“This indicates that individuals with a cannabis use disorder had lower perception of harm despite the higher measured severity,” Ahrens said.

The findings are significant in light of the widespread legalization of marijuana in New York, with regulators predicting the number of legal cannabis shops in NYC will double this year.

While it’s been good for business, critics say getting on the ganja train has led to a spate of subway crime in the city.

Despite its reputation for being the “safer” drug, recent studies have also shown smoking pot can increase your cancer risk and speed up aging.

“The biggest problem is that ever since it was made a Schedule 1 narcotic [in 1970], it has made it very difficult to do really well-devised, double-blind, placebo-controlled studies,” Dr. Ken Weinberg, chief medical officer of Cannabis Doctors of New York, previously told The Post.

“I don’t think there’s enough data.”

https://nypost.com/2025/04/22/health/what-weed-smokers-have-in-common-with-psychosis-patients-study/