Makary Considers More Cuts at FDA

 

According to an internal email, the agency may be in for more consolidation in areas including human resources, communications, travel and acquisitions.

FDA Commissioner Marty Makary is considering further consolidations at the agency—though without affecting groups that conduct inspections and review applications, according to a Friday report from Endpoints News.

In an email sent last Wednesday to FDA employees, Makary suggested that the agency will put human resources, acquisitions, travel, disclosures, communications, facilities, budget and IT operations under a “unified approach.” The goal, according to the email, is to “eliminate duplicative services, increase cross-communications across the FDA and deliver more consistent, efficient and responsive support” for its review teams.

It remains unclear if this move will mean additional layoffs and, if so, how many employees will be affected.

The impending changes, which haven’t been finalized yet, come as the FDA in recent months has struggled to deliver timely decisions on drug applications. Most recently, the regulator on Friday told KalVista Pharmaceuticals that it would not be able to release a verdict in time for its PDUFA target for the company’s oral drug candidate for hereditary angioedema.

According to the biotech’s release, the delay is due to “heavy workload and limited resources” at the FDA. The decision is now expected “within approximately four weeks,” the FDA told KalVista.

The FDA has already missed target decision dates for Novavax’s next-generation COVID-19 vaccine, GSK’s chronic obstructive pulmonary disease expansion for Nucala and Stealth BioTherapeutics’ Barth Syndrome treatment.

In March, Health and Human Services Secretary Robert F. Kennedy Jr. enacted a massive overhaul of the department, including 10,000 layoffs across its various units. The FDA took a heavy blow, losing around 3,500 staff, though Kennedy’s office has insisted that fired employees were not directly involved in product reviews.

https://www.biospace.com/fda/makary-considers-more-cuts-at-fda-amid-continued-delays

Sage’s Story Comes to ‘Good End’ With Up To $795M Acquisition by Supernus

 

Stifel analysts said the deal “feels like an unremarkable outcome for a company that was once one of the hottest stories in CNS.” Supernus’ offer beats Biogen’s unsolicited bid of about $7.22 per share, which arrived with a thud in late January.

Sage Therapeutics has agreed to be acquired by Supernus Pharmaceuticals for up to $795 million, marking a “good end” to the biotech’s story, according to analysts. The deal comes about five months after Sage balked at an unsolicited offer from its Zurzuvae development partner Biogen, which was valued at about $470 million.

The companies announced the acquisition Monday morning. Supernus is offering $8.50 per share in cash, or $561 million, at closing. The deal also includes a non-tradable contingent value right (CVR) of $3.50 per share, or $234 million, payable upon certain sales and commercial milestones. That brings the deal, which is expected to close in the third quarter, up to $12 per share in cash or $795 million.

Stifel analysts wrote in a note to investors that the deal “feels like an unremarkable outcome for a company that was once one of the hottest stories in [central nervous system disorders].” Nevertheless, it is a “good end” for the company, which had been facing myriad challenges including a lack of strategic control over lead asset Zurzuvae, the analysts said. The postpartum depression drug was developed with Biogen and received a limited label upon approval in August 2023.

Sage’s shares rose 36% in premarket trading Monday morning to $9.17. The stock has fallen 41% over the past year after hitting a price of over $90 in 2021.

Supernus’ offer beats Biogen’s unsolicited bid of about $7.22 per share, which arrived with a thud in late January. Sage immediately recoiled at the idea, suing Biogen to stop it. Stifel had assumed that Biogen would return with a “sweetened offer,” but that never happened.

Either way, Stifel did not voice much hope for Sage continuing on its own. “As we see it, for Sage to create value as an independent company, it would’ve required either a substantial acceleration in the PPD launch, or a surprise to the upside from the pipeline—the latter being a higher risk strategy, and a ‘show me story for the street, that would’ve burned significant capital,” the analysts wrote.

The deal does not put much weight in Sage’s pipeline, Stifel added. Supernus noted the potential of Zurzuvae to boost growth and diversify its portfolio. The drug, for postpartum depression, brought in $36.1 million in 2024 and has already taken home $13.8 million for the first quarter. The company also has three approved CNS medicines, Qelbree, ONAPGO and Gocovri, plus five other products.

Supernus and partner Biogen will have to significantly grow Zurzuvae sales for shareholders to see any benefit from the CVR. They will receive $1 of the CVR if Zurzuvae reaches $250 million in a calendar year between now and 2027; $1 if it reaches $300 million between now and the end of 2028; and $1 if sales reach $375 million between now and the end of 2030. Another 50 cents per share will be allocated if Zurzuvae is approved in Japan for major depressive disorder and achieves an initial commercial sale there.

The FDA declined to grant an indication for MDD, instead keeping the label narrowed to PPD.

Sage CEO Barry Greene said in the company’s announcement that the deal concludes a strategic review conducted by the board of directors and he is “confident this deal maximizes value for shareholders.”

https://www.biospace.com/business/sages-story-comes-to-good-end-with-up-to-795m-acquisition-by-supurnus

Roche, Prothena Push Parkinson’s Drug to Phase III Despite Mid-Stage Fail

 

Analysts at Jefferies give Roche and Prothena’s Phase III study just a 25% to 40% probability of success.

Roche and Prothena are forging ahead to late-stage studies for their investigational Parkinson’s disease antibody prasinezumab even though it missed the bar in a mid-stage trial late last year.

In a note to investors on Monday morning, analysts at Jefferies said that while this decision could be an incremental positive for Prothena, the payout will “take patience.” Given the prior failure, the analysts aren’t optimistic about the prospects of this new late-stage trial, giving it a 25% to 40% probability of success.

Prothena’s shares rose 7.3% as the markets opened Monday, trading at $5.40 versus $5.08 at market close on Friday.

“A primary debate here is whether the antibody approach is potent enough to ‘slow the spread’ of an intra-cellular protein,” Jefferies explained. In this case, the analysts questioned whether prasinezumab, a monoclonal antibody that works outside the cell, can efficiently engage and arrest its target alpha-synuclein, a small protein that causes progressive neuron death in Parkinson’s.

The news comes after the Ireland-based biotech announced last week that it was letting go of 91 employees from its California site. The layoffs, which will take effect Aug. 1, follow a Phase III AL amyloidosis stumble in May.

In its press announcement on Monday, Roche focused on what Chief Medical Officer Levi Garraway called “efficacy signals” for prasinezumab in the mid-stage trial. In particular, the pharma maintained that Phase IIb data point to a potential clinical benefit of the investigational antibody when used on top of symptomatic treatment in the disease’s early stages.

Roche also homed in on “positive trends” in motor progression at two years, as well as biomarker evidence to support the effect of prasinezumab on Parkinson’s disease biology.

“We would note Roche continues to refine and enrich the studies to try and find the best patient population,” the Jefferies analysts wrote on Monday, adding that “by changing things each time – this also modifies risk.” The failed Phase IIb study, for instance, was conducted on a patient group that had been modified from the Phase IIa trial, yet the pharma still “got mixed results,” as per Jefferies.

Roche and Prothena have yet to disclose details regarding the timeline and design of the Phase III program.

In December 2024, the partners announced that prasinezumab fell short of its primary efficacy endpoint in the Phase IIb PADOVA study, unable to significantly improve motor progression in patients with Parkinson’s disease. However, they argued that the magnitude of effect at the time—16% with a p-value of 0.0657—showed “potential clinical effect.”

Roche bought into the potential of Prothena’s prasinezumab in December 2013 in a $600 million deal, including a $45 million upfront payment.

https://www.biospace.com/drug-development/roche-prothena-push-parkinsons-drug-to-phase-iii-despite-mid-stage-fail

3 More States Diverge From CDC On COVID-19 Vaccine Recommendations

 by Zachary Stieber via The Epoch Times,

Officials from three states said on June 12 that pregnant women should still be able to receive COVID-19 vaccines, diverging from updated guidance from the Centers for Disease Control and Prevention.

Health officials with California, Oregon, and Washington state said in a joint statement that they “continue to recommend all individuals age 6 months and older should have access and the choice to receive currently authorized COVID-19 vaccines, with an emphasis on protecting higher risk individuals, such as infants and toddlers, pregnant individuals, and others with risks for serious disease.”

The CDC in May updated its immunization schedule for adults, removing a COVID-19 vaccine recommendation for pregnant women. Insurers typically only cover vaccines that are on immunization schedules, according to the American Academy of Family Physicians and other organizations.

The CDC also removed a recommendation for healthy children to receive a COVID-19 vaccine, although the childhood immunization schedule states that “where the parent presents with a desire for their child to be vaccinated, children 6 months and older may receive COVID-19 vaccination, informed by the clinical judgment of a healthcare provider and personal preference and circumstances.”

Officials have for several years been directing vaccine manufacturers to update their formulations on an annual basis. The CDC had been advising people to receive a shot each year, regardless of prior vaccination and infection.

Health Secretary Robert F. Kennedy Jr. said the changes were made because there is no clinical data to support a “repeat booster strategy.”

Wisconsin officials soon after said they were keeping in place COVID-19 vaccine recommendations for all individuals aged 6 months and older. Kirsten Johnson, Wisconsin’s health secretary, said that the current version of the vaccine “continues to be an important tool in preventing severe illness and death.” The Wisconsin Department of Health and Human Services has not responded to requests for citations.

“Under the leadership of Secretary Kennedy, HHS is restoring the doctor-patient relationship. If a parent desires their healthy child to be vaccinated, their decision should be based on informed consent through the clinical judgement of their healthcare provider,” a spokesperson for the U.S. Department of Health and Human Services (HHS) told The Epoch Times in an email.

“Secretary Kennedy has been clear: rebuilding trust in public health starts with transparency, medical autonomy, and access to unbiased information. Americans deserve to make health decisions based on their individual circumstances—not under pressure from politicized institutions or rigid, one-size-fits-all mandates.”

In the new statement, California, Oregon, and Washington state officials said that they “are committed to continuing to work with medical experts, professional organizations, and public health partners to ensure our recommendations reflect the best available science and safeguard the health of all of our residents.”

The officials noted that some medical groups, including the American College of Obstetricians and Gynecologists, recently expressed concern over the CDC’s removal of the COVID-19 vaccine recommendation for pregnant women.

“The COVID-19 vaccine is safe during pregnancy, and vaccination can protect our patients and their infants after birth,” Dr. Steven Fleischman, president of the college, said in a statement.

The U.S. Food and Drug Administration, which clears vaccines, says in package inserts for the three available COVID-19 vaccines that available data on the shots administered to pregnant women “are insufficient to inform vaccine-associated risks in pregnancy.” Known side effects of the vaccines include heart inflammation and severe allergic shock.

Apart from differing over the updated advice for pregnant women, the state officials said they are advising people to follow the CDC immunization schedules.

https://www.zerohedge.com/covid-19/three-more-states-diverge-cdc-covid-19-vaccine-recommendations

Wave Of USAF Tankers Depart America Amid Escalating Israel-Iran Conflict

 Israel's ongoing military campaign, Operation Rising Lion, has conducted coordinated precision strikes against Iran's nuclear infrastructure, crude oil export terminals, and high-value IRGC (Islamic Revolutionary Guard Corps) targets since late last week. The scope and sequencing of these strikes—outlined in a Wall Street Journal op-ed in October 2024—suggest objectives that go well beyond deterrence, aiming instead to pave the way for regime change in Tehran. 

Speaking Sunday, President Trump emphasized that the U.S. "is not involved" in Israel's strikes on Iran—adding, however, that "it's possible we could get involved."

"We're not involved in it. It's possible we could get involved. But we are not at this moment involved," Trump told ABC News' Rachel Scott. 

The president also took to Truth Social, positioning himself as mediator and de-escalator-in-chief, stating: "Iran and Israel should make a deal, and will make a deal."

Even though President Trump is intent on avoiding a direct confrontation with Iran, any IRGC shift from striking Israel to targeting U.S. interests or personnel in the Middle East would likely escalate the conflict and sharply increase the odds of American intervention.

Overnight, several aviation tracking websites, including Flightradar24 and Air Live, reported that dozens of U.S. Air Force tankers took off from the U.S. and headed towards Europe.

Destinations are unknown for some, but the Boeing KC-46A and KC-135 aerial refueling tankers are critical aviation assets that extend the operational reach, endurance, and flexibility of fighter jets. 

However... 

The repositioning of USAF aerial refueling tankers strongly indicates that Western military planners are bracing for a sustained or broadening conflict—measured in weeks, not days. If that's the case, market overservers should take note: JPMorgan warns Brent crude futures could surge into triple-digit territory if the conflict deepens. 

https://www.zerohedge.com/military/wave-usaf-tankers-depart-america-and-deploy-east-amid-escalating-israel-iran-conflict

'Market Rapidly Evolving Towards Positive Outcome In The Middle East'

 by Peter Tchir via Academy Securities,

While the fighting continues between Iran and Israel, the market is pricing in a positive outcome in the Middle East. Casualties continue to mount as Iran and Israel continue to attack each other, but an optimistic narrative is emerging.

• Israel has the upper hand militarily. Through a combination of traditional military force, intelligence, espionage and even sabotage, Israel has demonstrated the ability to target specific leaders and sites, with a high degree of success. Iran on the other hand, seems to be confirming what many of our GIG stated back when Iran launched a thousand or so missiles and drones against Israel – the weapons weren’t as effective against Israel’s Iron Dome and other defenses as feared.

  • The proxies have gone quiet. Rather than seeing Israel attacked on multiple fronts, the proxies have been quite quiet. Damage done to the proxies since Hamas attacked Israel on October 7th 2023, has been substantial.

• Iran is afraid to risk escalation to the point of direct U.S. involvement. While Iran has managed some strikes into Israel, the missile barrages seem dangerous, but not overwhelmingly so. Would they dare risk bringing the U.S. into more direct involvement? That would seem like a bad idea strategically from Iran, given their performance so far.

  • Straits of Hormuz likely to remain open. Threats about potentially trying to close this are largely being ignored (crude prices are slightly lower). Do they have the capability? Maybe, but that could bring the U.S. into the conflict in a more meaningful way. It would also not be surprising if China, via back channels, has messaged its preference to continue receiving Iranian oil.

• Regime change is on the table. From the messaging Israel is sending, it is clear that they believe there is a potential to kindle a regime change in Iran. We should all assume they have some degree of intelligence giving them the confidence to go ahead with that messaging. While the IRGC is allegedly still a major force to be reckoned with (we will come back to the word “allegedly” shortly) this would be a major positive development for the region. As the GIG has been pointing out for the past 2 years, with increasing emphasis, Iran has become the outlier and the “enemy” of the Middle East rather than Israel. Many of the nations want to move on and continue to develop post fossil fuel economies – just look at the deals President Trump struck on his recent trip to the region. One can even wonder if Regime Change might be easier to accomplish than knocking out all the Nuclear Capabilities?

While anything can still happen while the fighting continues, the optimistic narrative seems plausible and is very positive.

Which brings us to the point where we need to think about further ramifications. Since China, the Chinese military and the possibility of attacking Taiwan come up in so many of our meetings, we cannot help but wonder if China has some doubt about their own military:

• Russia turned out to be far less superior in the field than one would have expected on paper. They squandered a massive advantage in equipment early on, and while they continue to pound on Ukraine, they have failed to progress much beyond what they held before this all started.

• North Korean troops made headlines by fighting alongside Russians in Ukraine. By all accounts, they had incredibly poor tactics (World War I style charges, leading to their own slaughter). While North Korea has nukes and missiles, and we need to continue to take them seriously, their military seemed lacking in practice (at least what we witnessed in Ukraine).

• Iran’s “vaunted” missile systems. Not to diminish the deaths that have occurred, on both sides, but this has not been “shock and awe” levels of performance. While Iran has no air force, nor navy, so to speak, their air defense systems also seemed particularly vulnerable.

• China, a year or so ago, had dismissals in their “elite” rocket and missile forces. During the brief altercation between India and Pakistan, the Chinese fighter jets supposedly performed well, but the Chinese anti-air defenses did not (that is the intelligence scuttlebutt that came out of that fighting).

If you are Xi, it seems almost impossible that you aren’t at least a tiny bit worried that your own rapidly growing military is merely a paper dragon.

• Maybe this will encourage China to negotiate more fulsomely with the U.S. on the trade front?

  • In any case, hopefully given the recent talks and the focus on rare earths and critical minerals, the U.S. will embrace the policy of National Production for National Security which we touched on in this weekend’s On Shaky Ground.

The fighting continues, and there are risks, but what seemed like optimistic outcomes, now seems to be the most plausible outcomes.

At this rate, the FOMC meeting might be important, and we continue to expect the market to be surprised by a shift to dovishness from this Fed (as described in more detail in Sunday’s T-Report, linked above).

https://www.zerohedge.com/markets/market-rapidly-evolving-positive-outcome-middle-east

Trump to flood big cities like LA and NYC with ICE agents in ‘single largest Mass Deportation Program’

 President Trump announced plans to flood Democrat-run cities, namely New York, Los Angeles and Chicago, with new, larger waves of Immigration and Customs Enforcement agents to bring about the “single largest Mass Deportation Program in History.”

Trump highlighted the sweeping change targeting the majority-Democrat cities on Truth Social Sunday night as he praised ICE agents for their “incredible strength, determination, and courage.”

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President Trump announced that sanctuary cities in Democratic states will be flooded with ICE agents.REUTERS

“In order to achieve this, we must expand efforts to detain and deport Illegal Aliens in America’s largest Cities, such as Los Angeles, Chicago, and New York, where Millions upon Millions of Illegal Aliens reside,” Trump wrote.

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Trump specifically cited Democratic cities, claiming that their leaders were using illegal immigrants to do things like rig elections.Getty Images

“These, and other such Cities, are the core of the Democrat Power Center, where they use Illegal Aliens to expand their Voter Base, cheat in Elections, and grow the Welfare State, robbing good paying Jobs and Benefits from Hardworking American Citizens.”

Republican-run states like Texas, which is home to five of the largest cities in America, including Houston and San Antonio, were notably left out of the president’s post.

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Undocumented migrants make up half of America’s crop workforce.Matthew McDermott

None of the Lone Star State’s big urban centers, however, call themselves “sanctuary cities.”

“These Radical Left Democrats are sick of mind, hate our Country, and actually want to destroy our Inner Cities — And they are doing a good job of it!” the commander in chief added in his post.

“And that is why I want ICE, Border Patrol, and our Great and Patriotic Law Enforcement Officers, to FOCUS on our crime ridden and deadly Inner Cities, and those places where Sanctuary Cities play such a big role. You don’t hear about Sanctuary Cities in our Heartland!”

Trump previously pledged that “changes are coming” last week after admitting that his administration’s crackdown on immigration was massacring key American industries — namely farming and hospitality.

The Department of Agriculture estimates that nearly half of the 850,000 crop workers in the United States are undocumented, putting America’s food supply chain at risk of total collapse if all are deported.

While New York State is home to the largest sanctuary city in the country, it ranks first nationally in the production of many crops and products, including household staples like yogurt and cottage cheese, according to the New York Farm Bureau.

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ICE agents’ raids have scared many immigrants into hiding.Matthew McDermott

With Trump’s focus set on sanctuary cities, it is unclear how other parts of Democratic states may be impacted, or if ICE activity will primarily center on metropolitan areas going forward.

Even so, raids have already expanded beyond the fields with ICE agents turning up anywhere from courthouses to schools. The shift quickly scared many immigrant workers away from the public eye.

Data cited by the Wall Street Journal showed how immigrants’ purchasing habits dramatically shifted online. Large brands also saw a steep decrease in Hispanic customer traffic, with places that have fallen victim to raids like Home Depot seeing an 8.7% drop.

https://nypost.com/2025/06/15/us-news/trump-to-flood-big-cities-like-la-and-nyc-with-ice-agents-in-single-largest-mass-deportation-program-in-history/