New Evidence Links Progestogen Contraceptives to Brain Cancer Risk

 

• Women using progestogen contraceptives had a significantly increased risk of meningioma, the most common type of brain cancer.
• Consistent with other recent studies, injectable medroxyprogesterone was associated with the highest risk.
• The study extended the association to oral contraceptives and IUDs.

Women who used progestogen contraceptives had a significantly increased risk of meningioma, including oral and injectable progestogen formulations and intrauterine devices (IUDs), a large Danish study showed.

Eight of the 12 progestogen formulations included in the analysis had statistically significant associations with meningioma. Among the eight contraceptive formulations, odds ratios for meningioma versus non-users of progestogens ranged from 40% higher for levonorgestrel to more than four times higher for injectable medroxyprogesterone. Progestogen use within the past year was associated with the highest meningioma risk.

The excess meningioma risk disappeared 5 years after discontinuation of a progestogen contraceptive, reported Charlotte Wessel Skovlund, PhD, of the Danish Medicines Agency in Copenhagen, and colleagues in JAMA Network Open.

"The numbers needed to harm differed greatly depending on the specific progestogen used and the age group, with the highest risk observed for the oldest women," the authors stated. "Medroxyprogesterone showed the highest risk with relatively low numbers needed to harm, whereas all combined oral contraceptives, oral progestogen-only contraceptives, and IUDs had relatively high numbers needed to harm, especially among the youngest women. However, the present study suggests an increased risk of meningioma for several progestogens not previously associated with meningioma."

The study adds to and extends a large volume of evidence linking progestogens to meningioma. Over the past 5 years, multiple studies have shown significant associations between the contraceptives and the most common type of brain cancer, particularly injectable medroxyprogesterone.

• A French study involving 18,000 women undergoing intracranial surgery showed a 19-fold greater risk of meningioma among users of cyproterone acetate, which is not available in the U.S. An earlier study from France involving 250,000 women showed a sixfold greater risk of meningioma associated with the contraceptive.
• A U.S.-based study involving almost 90,000 women showed a meningioma relative risk of 2.43 with depot medroxyprogesterone versus non-users. The risk increased modestly to 1.18 among users of oral medroxyprogesterone acetate.
• Earlier this year, Swedish investigators reported a 76% higher odds for meningioma among users of hormonal contraceptives in general, driven by a fivefold increase with depot medroxyprogesterone. The odds declined to 1.34 for other progesterone contraceptives.

Late last year, the FDA approved a label change for depot medroxyprogesterone, adding a warning about meningioma risk. Additionally, the American College of Obstetricians and Gynecologists has published patient education and counseling information about the link between progestogen contraceptives and meningioma and advised its members to engage in shared decision-making discussions about contraceptive choices. The European Medicines Agency has assessed meningioma risk for various progestogen contraceptives and approved updated product information for cyproterone, nomegestrol, chlormadinone, and medroxyprogesterone, Skovlund and colleagues stated.

Evidence supporting the biological plausibility of the association comes from observation of progesterone receptors in up to 87% of all meningiomas. Multiple observational studies have described tumor growth during pregnancy in association with exogenous progesterone, followed by tumor regression after delivery or withdrawal of the hormonal treatment, the authors noted.

The Danish researchers continued the investigation with a case-control study covering the years 2000 to 2024. Using data from Danish national registries, they identified women with meningioma diagnoses and matched each case with 10 control patients without meningioma. Investigators then compared contraceptive use between the cases and control group. Data analysis included 1,473 women with meningioma and a control group of 14,717 women without meningioma.

The results showed a consistent pattern of increased risk of meningioma associated with use of progestogen contraceptives. Statistically significant odds ratios for meningioma emerged for:

• Injectable medroxyprogesterone: OR 4.55 (95% CI 2.19-9.45)
• Oral desogestrel: OR 1.73 (95% CI 1.17-2.56)
• Desogestrel-ethinyl estradiol: OR 1.66 (95% CI 1.31-2.10)
• Cyproterone: OR 1.61 (95% CI 1.00-2.59)
• Drospirenone: OR 1.58 (95% CI 1.05-2.37)
• High-dose levonorgestrel IUD: OR 1.58 (95% CI 1.28-1.94)
• Gestodene: OR 1.44 (95% CI 1.17-1.77)
• Levonorgestrel: OR 1.40 (95% CI 1.12-1.76)

The analysis yielded nonsignificant associations for norethisterone combination (OR 1.38, 95% CI 0.77-2.47), low-dose levonorgestrel IUD (OR 1.14, 95% CI 0.59-2.22), norgestimate (OR 1.04, 95% CI 0.70-1.54), and norethisterone (OR 0.95, 95% CI 0.57-1.57).

Disclosures

Skovlund and co-authors reported no relevant financial disclosures.

Primary Source

JAMA Network Open

Source Reference: Lundstrøm NH, et al "Contraceptive progestogens and incident meningioma" JAMA Netw Open 2026; DOI: 10.1001/jamanetworkopen.2026.22603.

https://www.medpagetoday.com/hematologyoncology/braincancer/122030

7 FDA decisions to watch for in Q3

 

Many of the FDA’s decisions this quarter involve applications that have previously been delayed, declined or outright rejected, including one for an mRNA vaccine that became the center of controversy earlier this year.

The third quarter of 2026 is looking like a busy one for the FDA, with seven noteworthy decisions on its docket, including one that could mark a first in Alzheimer’s disease care and another that could justify a recent high-value buyout.

Read below for more.

Vera aims to challenge big names in IgAN arena

In one of Q3’s earliest decisions, Vera Therapeutics is looking to join the IgA nephropathy game with its investigational fusion protein atacicept. The drug is currently under FDA review with a target action date of July 7.

Backing atacicept’s application are data from the Phase 3 ORIGIN 3 study, in which the drug elicited a 46% decrease in proteinuria at 36 weeks versus baseline, according to a November 2025 press release. Atacicept also eliminated blood in the urine in 81% of patients.

These data paint a “compelling profile” for atacicept, Guggenheim Partners said in a Nov. 6 note to investors, strengthened even further by the drug’s “excellent safety profile that is comparable to placebo.”

If approved, atacicept would compete with Otsuka Pharmaceuticals’ APRIL inhibitor Voyxact, which won the FDA’s greenlight in November last year, and Novartis’ complement inhibitor Fabhalta. Vertex Pharmaceuticals, meanwhile, is close on Vera’s heels with its own fusion protein povetacicept, which has an FDA action date of Nov. 30.

Moderna’s mRNA flu shot nears D-day after sparking controversy

Moderna’s investigational flu vaccine made headlines in February when the FDA hit the company’s application with a refusal-to-file letter, declining even to give the submission the time of day. The agency at the time said that Moderna’s study used a comparator group that “does not reflect the best-available standard of care.”

A few days later, after strong blowback and a hastily arranged type A meeting with the biotech, the FDA reversed course and accepted an adjusted application for review. This time, Moderna is seeking full approval of its mRNA vaccine, dubbed mRNA-1010, in adults 50 to 64 years, and accelerated approval in people 65 and older. A decision is expected on or before Aug. 5.

Moderna is supporting the vaccine with many late-stage studies establishing its efficacy. One readout in June 2025 showed the mRNA shot was 26.6% more effective than a licensed comparator flu vaccine in adults 50 years and up.

Last month, the FDA’s Vaccines and Related Biological Products Advisory Committee unanimously recommended the mRNA flu shot’s full approval for adults aged 50 through 64, and accelerated approval for those 65 and up.

Capricor hopes for cell therapy comeback in Duchenne

By Aug. 22, the FDA is expected to release its decision on deramiocel, Capricor Therapeutics’ investigational cell therapy for Duchenne muscular dystrophy.

An approval here would serve as a vindication for deramiocel, which was initially rejected by the FDA last summer. At the time, the regulator said Capricor’s data package for the product failed to satisfy the “statutory requirement for substantial evidence of effectiveness.”

After deramiocel aced a Phase 3 trial, the FDA lifted its complete response letter in March, allowing the application to once again move forward. Capricor is seeking full approval of the candidate.

Deramiocel uses a rare subset of allogeneic cells drawn from the heart that can modulate the immune response and reduce fibrosis. The treatment works by helping maintain the function of cardiac and skeletal muscles. Data from the Phase 2 HOPE-2 study, which supported deramiocel’s initial application, demonstrated significant improvements in upper-limb performance and cardiac function over placebo.

Capricor’s resubmission now also includes data from the Phase 3 HOPE-3 study, which in December hit both its primary and secondary endpoints, showing statistically significant benefits in upper-limb function and a slowed decline in cardiac function as measured by left ventricular ejection fraction. Deramiocel also slowed disease progression and boosted overall functional performance, according to further data revealed in March.

Ultragenyx times two: Pair of gene therapies up for approval

Q3 is shaping up to be crucial for Ultragenyx, with two gene therapies lined up for FDA verdicts: DTX401 for glycogen storage disease type 1a (GSD1a), set for Aug. 23, and UX111 for Sanfilippo syndrome type A, due Sept. 19.

The upcoming decision date is especially pressing for UX111, which has already been rejected once. The FDA declined to approve the gene therapy in July 2025, citing manufacturing issues. Ultragenyx emphasized at the time that the denial was due to reasons “not directly related to the quality of the product.”

UX111 uses an adeno-associated virus (AAV) vector to deliver a functioning copy of the SGSH gene, which in patients with Sanfilippo syndrome type A is mutated, giving rise to a broad array of neurological and developmental symptoms. Around 1 in every 50,000 to 250,000 people globally have one of the four types of Sanfilippo syndrome, with A being the most common.

Meanwhile, GSD1a is caused by pathogenic mutations to the G6PC gene, produces an enzyme, G6Pase, that plays a role in the release of glucose from its stores. A deficiency in this activity can lead to severe hypoglycemia in between meals, as well as other complications that make the condition life-threatening. Patients with GSD1a are treated with cornstarch, which serves as an exogenous source of glucose.

DTX401 works by stabilizing the expression and activity of G6Pase. In Phase 3 development, the gene therapy led to a “significant and clinically meaningful” decrease in patients’ need for daily cornstarch intake, while also minimizing hypoglycemia episodes, according a company news release in February.

Biogen, Eisai ride out 3-month delay for starter dose of Leqembi Iqlik

After extending its review for 3 months, the FDA set a decision date of Aug. 24 for Eisai and Biogen’s application for the use of an under-the-skin formulation of their Alzheimer’s disease therapy Leqembi to initiate patients onto the treatment.

The FDA has already signed off on a subcutaneous version of Leqembi, now marketed as Leqembi Iqlik. However, the September 2025 approval only allows the use of the injection for maintenance treatment—that is, patients should first have completed 18 months of intravenous Leqembi.

A nod for Leqembi Iqlik in the induction setting would make it the first anti-amyloid therapy for at-home dosing throughout the entire treatment journey, the companies said in a January news release.

At the J.P. Morgan Healthcare Conference that same month, CEO Chris Viehbacher acknowledged that a nod is “going to be extremely important” and would help Leqembi compete with Eli Lilly’s Kisunla, which is infused monthly, versus Leqembi’s biweekly schedule. Kisunla’s current convenience edge “is going to go away once we have a subcutaneous formulation,” Viehbacher said.

Nuvalent nears NSCLC ruling for drug that attracted GSK buyout

Fresh off its $10.6 billion acquisition agreement with GSK, Nuvalent is nearing a potential approval for its ROS1 inhibitor zidesamtinib for the treatment of non-small cell lung cancer (NSCLC). The FDA’s verdict is expected on or before Sept. 18.

Nuvalent is backing its application with data from the Phase 1/2 ARROS-1 study. A readout in September 2025 showed that zidesamtinib elicited a 44% objective response rate in patients who had undergone prior treatment with a tyrosine kinase inhibitor. This figure improved to 51% when focusing on those who had only one previous line of treatment.

Zidesamtinib was one of the two stars of last month’s GSK takeover, alongside the ALK blocker neladalkib, also being proposed for NSCLC. The pharma believes both molecules have “multi-blockbuster potential,” according to GSK’s June 9 announcement. Truist Securities in a note the same day projected combined peak revenues for the two drugs to hit $3.5 billion.

Scholar Rock gives muscle atrophy drug another try

Capping off this list is Scholar Rock’s myostatin blocker apitegromab, which the biotech is proposing for the treatment of spinal muscular atrophy. The FDA’s target action date is September 30.

Apitegromab is a monoclonal antibody that inhibits the activation of myostatin, a protein that works to negatively regulate the growth of muscles. By blocking myostatin, apitegromab improves muscle mass and strength, as well as overall patient function and quality of life, according to Scholar Rock’s website.

Scholar Rock bore this out in the Phase 3 SAPPHIRE study, which in October 2024 showed significant motor improvements in patients treated with the antibody versus placebo.

In September 2025, however, the FDA handed Scholar Rock a rejection, flagging violations at a Novo Nordisk–owned manufacturing site where apitegromab was supposed to be produced. Other applications have also been tripped up by this particular plant, including Regeneron’s high-dose Eylea.

In March, Scholar Rock refiled its package for apitegromab, noting that while it will continue to engage the Novo facility, the biotech will also enlist a second fill-finish facility in the U.S. to “strengthen the apitegromab supply chain.”

https://www.biospace.com/fda/7-fda-decisions-to-watch-for-in-q3

What Did He Just Say?

 by Steve Watson via Modernity News,

In a parliamentary clash exposing deep failures in the justice system, Conservative MP Katie Lam confronted the Government over whether grooming gang perpetrators would serve their already lenient prison terms in full.

The minister's reply has sparked widespread fury, highlighting a complacency that victims and the public find utterly unacceptable.

When Lam asked for assurances on full sentences, Justice Minister Jake Richards pointed to prison capacity, stressing the need to ensure serious offenders "serve time at all" amid prison shortages and building programs.

Lam slammed the reaction: "He wouldn't even commit to that. In fact, he seemed to suggest that we should be grateful that these men are serving time in prison at all because of a lack of prison places. What planet are these people living on?"

She continued, "Even if we're facing a shortage of prison places, how can it possibly be the case that grooming gang perpetrators aren't amongst the highest priority offenders...?"

"Ensuring that these vile men serve out their sentences isn't a nice-to-have. It's the bare minimum," Lam stressed.

In a piece for GB News, Lam further outlined "This week, Parliament debated the early release of rapists and child groomers from prison. It's appalling that this subject was even up for discussion."

She continued: "It's clearly true that those who've committed such heinous crimes should, at the very least, serve out their full prison sentences. But under this Government's prison plans, vile criminals like these are having their sentences cut short. They're being allowed back onto the streets after just a few years behind bars."

"Many Labour MPs still don't seem to have grasped just how horrific these crimes were and just how dangerous the men who committed them are. It's terrifying that people like this are in charge of making decisions about who goes to prison, who stays there, and for how long." Lam further urged.

This comes as one grooming gang ringleader - stripped of British citizenship - faces imminent release but cannot be deported back to Pakistan due to legal loopholes.

The inability to remove such individuals underscores deeper systemic issues with immigration enforcement, citizenship revocation, and prioritizing foreign offenders' "rights" over victim safety and public protection.

Referencing a recent West Yorkshire case, Lam detailed: "In June, twenty perpetrators were convicted of the rape and abuse of three girls... One of the girls was just 12 years old when this gang began to prey on her. Abbas Kaji, one of the offenders, was sentenced to just seven years for rape; Mohammed Ishtiaq Hussain was sentenced to just eight. The idea that these men could be out on the streets even sooner is appalling."

The grooming gangs scandal represents one of Britain's gravest institutional betrayals. These groups terrorized communities across the UK, with authorities often ignoring, suppressing or downplaying the ethnic and cultural patterns - predominantly Pakistani Muslim men targeting white girls - out of fear of racism accusations.

Lam has been vocal on the human cost. She referenced survivor Fiona Goddard, who received notice that her abusers - sentenced to 16-20 years in 2019 - could be eligible for early release: "The hard-won justice that she secured in court is being snatched away from her."

Calls for whole-life sentences, proper inquiries without blind spots on race and religion, and accountability for past cover-ups have grown, amplified by independent reports and public pressure.

The priority should be crystal clear: protect British children, enforce real justice, and reject any notion that jailing child rapists is an optional luxury.

Short sentences, early releases, and evasive answers only deepen the sense of betrayal that has defined this scandal for decades.

Britain needs a justice system that puts victims first and deters monsters - not one that debates basic incarceration as if it's a favor.

https://www.zerohedge.com/political/what-did-he-just-say

US Stocks Give Up Jobs Report-Related Gains as Semis Pull Back

 

US equities lost earlier gains as technology stocks trailed the S&P 500 Index for a second straight day, continuing the downturn after the rally seen in the previous quarter.

The S&P 500 Index fell 0.01% by 11:45 a.m. in New York, erasing gains from a cooler-than-expected employment report that dimmed prospects of an interest-rate hike from the Federal Reserve. Meanwhile, the tech-heavy Nasdaq 100 Index fell 1.1% as semiconductor company stocks tumbled.

https://www.bloomberg.com/news/articles/2026-07-02/us-stocks-muted-as-traders-wait-on-jobs-data-for-rate-path-clues

'Something Has Gone Completely Wrong': Palantir's Alex Karp Goes Ballistic On OpenAI, Anthropic

 On Wednesday, Palantir CEO Alex Karp delivered a blistering critique of frontier AI labs, accusing them of having an "effing insane" business model that leaves enterprises paying escalating token costs for limited value while risking their proprietary data and intellectual property. He said that top AI labs such as Anthropic and OpenAI were misleading corporate partners - "overselling" the risks of AI while at the same time offering their most powerful models to companies and governments worldwide. 

When CNBC host Becky Quick said "You sound pretty angry," Karp replied: "This is the voice of American business that is being channeled through me," he told CNBC, joking later that he might "get kicked out of the room."

Karp's comments come amid a "revolt" against U.S. AI labs - driven by a combination of high costs, questionable ROI, and increasing regulatory headwinds which have driven some major U.S. companies to cheaper Chinese alternatives, creating multiple pressure points for OpenAI, Anthropic, and others.

"Something Has Gone Completely Wrong"

Karp slammed the token model used by Anthropic and OpenAI - saying "I'm not throwing shade at them, but something has gone completely wrong," he said. "The basic view among enterprises in this country is I'm going to chillax and waste my time with tokens."

He argued that that labs were overselling risks while simultaneously pushing powerful models, and that companies were effectively paying a "wealth tax" that transferred their "alpha" (competitive advantage) to third parties. On national security, he warned: "Are we really going to outsource the battlefield of this country to the consensus view in Silicon Valley? That is effing insane."

The remarks aligned with a 9-point "AI sovereignty" manifesto Palantir posted on X the day before, which criticized "tokenmaxxing" for incentivizing disposable scripts over robust systems and urged institutions to retain control over their data, model weights, and competitive edge.

Via X: 

Our thoughts on the importance of AI sovereignty.

1. Your AI sovereignty dictates your institution’s future. Sovereignty is the precondition for choice. Relinquishing sovereignty transfers the future choices of your institution to others, who are likely to exploit it for their gain and your loss.

2. Data retention is your treasure. Transfer it at your own peril. Your ability to win is dictated by your ability to recognize and use your unique edges, and you keep winning by compounding the underlying data to generate new insights. Transferring that data hands over access to your pre-existing winning plays and yields the means of production for new ones.

3. Tokenmaxxing hijacks your value orientation and decreases your institutional fortitude and intelligence. The pursuit of high token usage incentivizes disposable scripts over robust software — with the addictive feeling of false progress. There is a reason why those selling tokens refuse to charge based on value.

4. Controlling your weights is controlling your fate. Weights are the distilled form of hard-won, accumulated institutional knowledge. If you let others control your weights, you are allowing them to migrate the alpha of your business to theirs.

5. There is no contradiction between sovereignty and alpha. The architecture that maximally preserves sovereignty is one that enables institutions to own their tribal knowledge, and to compound it as alpha.

6. Politicizing the technical issues involving sovereignty is what your adversary wants. Techno-politicization is the wellspring of false sovereignty. Techno-politicization drives decisions that seem to reduce dependency, but ultimately limit agency — especially on the battlefield in the West.

7. Real expertise is existential. Allowing politics or favoritism to determine your technical decisions rewards whoever is best at politics, not whoever is right. Listen to those closest to the problems, not those speaking most compellingly about them.

8. Learn from institutions that are winning or that have consistently delivered. Institutions facing existential threats do not have the luxury of making technical decisions based on political preferences.

9. Only listen to institutions, countries, and people who have a proven record of being right. A track record of correctness is the best and only signal for future correctness. Judging something as right or wrong based on who you like is exceedingly misguided.

"Controlling your weights is controlling your fate," the manifesto stated. "If you let others control your weights, you are allowing them to migrate the alpha of your business to theirs."

Karp noted Palantir's expanded Nvidia partnership, which enables custom, sovereign AI deployments where customers retain control over compute, models, data, and weights - a direct counter to the metered frontier API model.

Watch CNBC's full interview with Palantir CEO Alex Karp

The Cost-Driven Shift To Chinese Models

As we've been noting, high token prices and mixed returns have prompted several U.S. companies to adopt or explore Chinese open-weight models:

• Microsoft is considering a Microsoft-hosted, fine-tuned version of China's DeepSeek V4 (or another open-source model) as a lower-cost engine for its Copilot Cowork agentic tool, as it moves toward usage-based pricing.
• Coinbase CEO Brian Armstrong revealed the company cut internal AI spending by nearly 50% by defaulting engineers to Chinese open-weight models (Zhipu AI's GLM 5.2 and Moonshot AI's Kimi series) via an internal gateway, while maintaining high usage.
• Cursor, a fast-growing AI coding startup, built its Composer 2 model on top of Moonshot AI's Kimi K2.5 (backed by Alibaba).

Data from OpenRouter shows Chinese models capturing a rapidly growing share of global token consumption - in some periods exceeding 60% among top models - as enterprises seek cost relief without fully sacrificing capability.

Karp had warned against underestimating China's progress; these examples illustrate the trend in real time.

Watch the entire interview below:

https://www.zerohedge.com/ai/something-has-gone-completely-wrong-palantirs-alex-karp-goes-ballistic-openai-anthropic