uniQure’s Regulatory Progress Sparks Optimism for ‘Desperate’ Huntington’s Space

 

Analysts reacted positively to the news that uniQure is in alignment with the FDA on an accelerated approval pathway and on target for a Q1 2026 submission for its one-time gene therapy for Huntington’s disease—but patients have been here before.

When uniQure CEO Matt Kapusta speaks to patients with Huntington’s disease, he hears a sense of “deep desperation.”

Currently, people with Huntington’s—who number around 30,000 in the U.S.—are only offered drugs that can manage symptoms, which include movement abnormalities and cognitive impairment, “and those drugs really don’t work very well,” Kapusta told BioSpace. “There’s no disease-modifying treatments for them.”

uniQure is hoping to change that. Last fall, the Massachusetts-based biotech announced alignment with the FDA on “key elements” of an accelerated approval pathway for AMT-130, a one-time gene therapy for Huntington’s. These elements include the use of natural history external controls as a comparator and change in the composite Unified Huntington’s Disease Rating Scale (cUHDRS) as an intermediate clinical endpoint. The cUHDRS measures the cognitive, motorial, psychiatric and behavioral symptoms of Huntington’s disease, Kapusta explained. For AMT-130, which is currently in Phase I/II studies, this would negate the need for another trial before uniQue can file for approval, and Stifel analysts at the time called the alignment “a best case scenario” for the company.

On Monday, uniQure shared another regulatory update, communicating that it has “reached alignment with the FDA on several key components of the statistical analysis plan and chemistry, manufacturing and controls [CMC] information that will support” a biologics license application (BLA) in the first quarter of 2026. If successful, uniQure plans to launch the product before the end of next year.

AMT 130 represents “the first potentially disease modifying treatment that could be available for [patients],” Kapusta said.

Much of this, however, could hinge on three-year topline data which Kapusta expects to read out in September. At 24-months, a higher dose of AMT 130 slowed disease progression by 80% versus external controls, uniQure reported last July. The BLA will be based on this higher dose cohort, and the company will also analyze changes in neurofilament light—an accepted neurodegenerative biomarker—as supporting evidence. In September, Kapusta said the company will be seeking “consistency” with the two-year data.

“If we’re able to demonstrate in treated patients at three years after a one-time administration of AMT 130 that there’s meaningful slowing of disease progression compared to this very closely matched external control cohort, I think that would be immensely powerful, and I think potentially supportive of a conditional approval,” he said.

Typically, Kapusta said, early manifest patients—like those enrolled in uniQure’s study—lose around half a point on the cUHDRS scale per year. At two years, external controls in uniQure’s Phase I/II study had lost around one point, while patients treated with AMT 130 lost only 0.2 points.

“If you extrapolate these things, what you’re really doing is you’re giving back to patients potentially years of their life, years of career development, years of weddings with their children, or birth of grandchildren, bar mitzvahs, sweet sixteens,” he said, “That’s what we’re hoping we can demonstrate in the third quarter.”

uniQure’s news generated some buzz on Wall Street, with H.C. Wainwright assigning AMT-130 a 75% probability of success, “with anticipated approval in 2026E.”

William Blair, meanwhile, called the regulatory update “favorable” both for uniQure and the broader gene therapy space, “as it demonstrates the FDA’s continued flexibility regarding registrational pathways for transformative therapies for rare diseases with a high unmet need.”

Kapusta echoed this sentiment, saying that uniQure has not noticed a difference in terms of the company’s FDA interactions occurring before and after the administration turnover this year. “There’s still senior people that are attending our meetings from [CBER’s] office of therapeutic products . . . and we continue to see significant engagement and productive, constructive interactions with the FDA,” he added.

While Kapusta said there has been a “knee jerk” reaction to past comments made by new Center for Biologics Evaluation and Research director Vinay Prasad regarding accelerated approvals, “It definitely seems that in comments he’s made to his own FDA staff, and comments that he’s made in other interactions, that he appears to be making it clear that he supports regulatory flexibility as it relates to innovative medicines in very high needs in rare diseases.”

Indeed, on Tuesday, Prasad said the FDA plans to “rapidly make available” rare disease drugs, making use of surrogate endpoints to get promising medicines to patients before they clear the traditional efficacy bar for authorization. He made these remarks during a keynote speech organized by the National Organization for Rare Disorders. Prasad’s comments largely echo those of his boss. In April, during an interview with former Fox News journalist Megyn Kelly, FDA Commissioner Marty Makary introduced plans for a “conditional pathway” that would potentially allow for the approval of rare disease drugs based on a “plausible mechanism.”

A Precedent of Disappointment

As uniQure and analysts express optimism—albeit gaurded—the Huntington’s space has been here before, with myriad late-stage assets nearing the regulatory finish line only to falter.

Five years ago, the community pinned its hopes on Roche’s antisense oligonucleotide tominersen. The ASO was designed to lower levels of the huntingtin (HTT) gene, particularly mutant HTT, which plays a crucial role in the development of the disease. Tominersen had shown great promise in Phase II, but in March 2021, Roche discontinued a Phase III trial of the drug after it ultimately failed to elicit higher efficacy than placebo, and actually led to worse outcomes when given more frequently. 2021 was a particularly bad year for the Huntington’s space, as Wave Life Sciences likewise shelved its two lead ASOs after they failed to elicit a therapeutic effect.

But Huntington’s-focused companies aren’t giving up. Wave is back with a next-gen ASO, WVE-003, that targets a single-nucleotide polymorphism found on mutant HTT mRNA. Like uniQure, Wave is targeting accelerated approval for its candidate, having “initiated engagement” with regulators regarding a clinical development path, CEO Paul Bolno told BioSpace in November 2024.

And at least on a global scale, uniQure has some competition to bring the first disease-modifying drug for Huntington’s to the market. In September 2024, Prilenia Therapeutics announced that the European Medicines Agency had accepted its marketing authorization application for pridopidine, a “highly selective and potent” agonist of the sigma-1 receptor, which is highly expressed in the brain and spinal cord and regulates several key processes that are commonly impaired in neurodegenerative diseases.

Prilenia expects an opinion from the European regulator in the second half of this year, a company spokesperson told BioSpace in November 2024.

A breakthrough can’t come soon enough for patients. Huntington’s is a dominantly transmitted neurodegenerative disorder and children of HD gene carriers have a 50% chance of inheriting the disease. Kapusta described a situation in which an individual has watched the degeneration of their parent—and possibly even acted as a caregiver. “If this is a patient that has been genetically confirmed, they know it’s 100% penetrative; they’re going to develop the disease, and they’re going to have to relive that movie as the main actor,” he said. “So right now, anything for them would give them hope.”

https://www.biospace.com/drug-development/uniqures-regulatory-progress-sparks-optimism-for-desperate-huntingtons-space

Regenxbio Fails To Best Sarepta’s Elevidys With New Data for DMD Gene Therapy

 

Interim results from a small group of children in a Phase I/II trial are essentially in line with that of Elevidys, according to BMO Capital Markets analysts.

In the race to bring another Duchenne muscular dystrophy treatment to the market, Regenxbio showed new interim Phase I/II data Thursday for its gene therapy RGX-202.

The data, which came from five patients aged 6 to 12 years old in the AFFINITY DUCHENNE trial, demonstrated “consistent, robust microdystrophin expression,” according to the biotech’s press release. The trial tracked patients at 9 and 12 months post treatment.

Analysts from BMO Capital Markets saw the results as being essentially in line with Sarepta’s Duchenne muscular dystrophy (DMD) gene therapy Elevidys, first approved in June 2023. “Although certain [RGX-202] functional improvements appear slightly higher than Elevidys, given the high variability across patients/control and lack of placebo arm, we don’t think the efficacy difference between RGNX/Elevidys is material or could drive/prove differentiated clinical outcomes,” the analysts wrote Thursday morning.

Regenxbio’s stock was down about 16% at the time of publication.

AFFINITY DUCHENNE’s primary endpoint is safety, with a biomarker endpoint of microdystrophin expression. Regenxbio reported no serious adverse effects. Notably, patients taking RGX-202 are given immunosuppressants to tamp down on those effects, something not done with Elevidys, according to the BMO analysts.

As for efficacy, RGX-202 “continues to demonstrate evidence of positively impacting disease trajectory,” according to the company, showing improvements on the North Star Ambulatory Assessment and timed function tests, including time to stand, 10-meter walk-run and time to climb, which exceeded external natural history controls.

Regenxbio is planning a biologics license application sometime in mid-2026 through the FDA’s accelerated approval pathway, with an eye toward an approval in the first half of 2027, according to materials distributed by the company at its data readout.

Regenxbio and Sarepta are close competitors in the DMD space. In 2020, Regenxbio sued Sarepta for infringement of a patent on an adeno-associated virus (AAV) gene therapy cell culture technique. In 2024, a Delaware district ruled in favor of Sarepta, stating that the cell culture technique was not patentable.

The safety of DMD gene therapies has come under a harsh glare after a patient taking Elevidys died of acute liver injury in March. While safety appears to be a positive in Regenxbio’s trial, the BMO analysts noted that “heavy” immunosuppression carries its own risks, and that the viral vector that Regenxbio uses has had its own mortality concerns.

https://www.biospace.com/drug-development/regenxbio-fails-to-best-sareptas-elevidys-with-new-data-for-dmd-gene-therapy

Sarepta Wins FDA’s Platform Tech Designation, ‘Critical Shift’ in Gene Therapy Development

 

The Platform Technology Designation, which predates the current FDA leadership, is designed to streamline the drug development and review process, particularly for rare diseases.

The FDA granted Sarepta Therapeutics its first publicly documented Platform Technology Designation for a viral vector, called rAAVrh74, that the company uses in its investigational gene therapies.

Draft guidance for the designation was issued in 2024 under the Biden administration. Drug makers that receive the designation can use a “platform technology” to make more than one drug or biologic, with the aim of streamlining reviews and creating predictability for new drug applications created using the same technologies.

The regulator’s official recognition of Sarepta’s platform represents “a game-changing move” for cell and gene therapies, Audrey Greenberg, a venture partner at the Mayo Clinic and biopharma commentator, wrote in a LinkedIn post on Wednesday evening. “This marks a critical shift,” she continued, “away from single-asset risk, toward shared components and repeatable systems.”

The designation is a “huge step toward modular, scalable development,” Greenberg added, and the FDA’s move on Wednesday paves the way for “a plug-and-play future for gene therapy.”

Analysts at William Blair agreed, writing in a Wednesday note to investors that the Platform Technology Designation encourages the use of “standardized platforms across drug development,” in turn “streamlining development of therapeutics.” The overall effect, they continued, is to “reduce the burden on developers and regulators.”

For Sarepta in particular, the designation is “favorable,” according to William Blair, as it should help the company “accelerate the development of its follow-on gene therapy programs” while also lowering early R&D expenses. According to the biotech’s announcement, the viral vector rAAVrh74, is being used in its investigational gene therapy for limb-girdle muscular dystrophy (LGMD). Importantly, as noted by Jeffries analysts in a Thursday morning note, rAAVrh74 is the same vector used by Sarepta’s already-approved Duchenne muscular dystrophy gene therapy Elevidys.

Sarepta is also using the vector platform for at least two other LGMD therapies, as per William Blair, but these assets will be made through a different manufacturing process. “It is unclear if the platform designation could be leveraged for these investigational candidates in the future,” the analysts wrote.

Wednesday’s designation comes as FDA leaders in recent weeks have expressed support for some regulatory flexibility for rare diseases and gene therapies. Commissioner Marty Makary, for instance, said in an April interview on the Megyn Kelly Show that the agency could determine if a drug candidate has a “plausible mechanism” when considering it for approval, especially for diseases affecting “a small number of people.”

If an investigational therapy “makes sense physiologically” and has a mechanism that is “scientifically plausible,” the FDA could then approve this treatment on “a conditional basis,” Makary said.

Makary has so far been consistent with his support for accelerating drug development for rare diseases, Jefferies said in an investor note on Wednesday. In a conference held by the firm, Makary emphasized the need to “build on the successes of creative regulatory pathways, lending support to surrogate endpoints,” the note read.

And on Tuesday, during an event organized by the National Organization for Rare Disorders, newly installed Center for Biologics Evaluation and Research director Vinay Prasad—who has often been critical of accelerated approvals—committed to giving rare disease patients rapid access to “products that are even small steps forward.”

https://www.biospace.com/fda/sarepta-wins-fdas-platform-technology-designation-marking-critical-shift-in-gene-therapy-development

Netanyahu's Rule In Peril As Ultra-Orthodox Move To Dissolve Knesset Over Conscription Of Haredim

 Israeli Prime Minister Benjamin Netanyahu's ruling government coalition is under a new threat of being toppled after the largest opposition party introduced a measure to dissolve the parliament -- and key ultra-Orthodox political and spiritual leaders, angered over the prospect of ultra-Orthodox youth being included in the country's military draft, are supporting the move to force new elections. 

Since Israel was created in 1948, ultra-Orthodox Haredi Jews have been exempted from the military conscription that's imposed on almost all other men and women. Haredi men typically dedicate their entire lives to religious study in seminaries called Yeshivas. With Israel waging a multi-front war encompassing Gaza, the West Bank, Lebanon, Syria, Yemen and Iran, the exemption has become increasingly unpopular with the other segments of Israeli society that must heed the call.

Protesters of Haredim draft exemptions outside the Israeli Defense Force induction center push mock coffins (Mothers at the Front)

In June 2024, Israel's Supreme Court ruled that the government must start drafting the Haredi. "At the height of a difficult war, the burden of inequality is more than ever acute," wrote the court in a unanimous decision. The Haredi erupted in protests -- some of which turned violent. Since last summer, ultra-Orthodox politicians, including the non-Haredi variety, have been pushing for the Knesset to overcome the high court ruling by codifying the exemption. 

On Wednesday, leading opposition party Yesh Atid advanced a bill calling for the Knesset's dissolution. The first vote on the measure is expected next week. “This Knesset is finished,” said Yesh Atid leader Yair Lapid. “It has nowhere else to go. All that it has brought to the people of Israel is pain, and disasters, and bereavement and crises.” That move cam on the same day that two spiritual leaders of a faction of the ultra-Orthodox United Torah Judaism Party, Rabbis Dov Lando and Degel Hatorah, instructed members to move forward with an attempt to topple Netanyahu's government over the draft issue.  

Ultra-Orthodox Israeli Jews -- many of whom reject Zionism and the creation of the State of Israel -- demand that their draft exemption continue (Anadolu Agency)

There are 120 seats in the Knesset, and Netanyahu's coalition controls 68 of them. Of his coalition, 18 come from Israel's two main ultra-Orthodox parties. They've already been boycotting votes for several weeks. Though he's proven his ability to dodge political bullets time and time again, Netanyahu would likely be ousted in a new election: A new survey projected Netanyahu's coalition would garner only 46 to 48 seats, compared to 62 to 72 for an opposition bloc led by former Prime Minister Naftali Bennett, who has repeatedly opposed the draft exemption. 

The ultra-Orthodox have rattled their Knesset-dissolution sabers before, but this move is being perceived as far more serious -- as a measure is on the table with the backing of the parties' religious advisors. On Wednesday afternoon, Netanyahu's office assured that a crisis can be averted, saying "there is a way to bridge the gaps on the draft issue.” However, any such bridging threatens to trigger outrage among the non-Haredi whose young family members continue facing death and loss of limbs in Gaza and elsewhere as they're forced to serve.  

Rabbi Dov Lando, who chairs an ultra-Orthodox faction's Council of Torah Sages, directed Knesset members to support dissolving parliament and forcing new elections (Shlomi Cohen/Flash 90 via Times of Israel)

The internal division comes as the country is steadily treading deeper into international-pariah territory, owing to growing convictions that the country's military campaign in Gaza has inflicted a wildly disproportionate toll on civilians. In the latest indicator of that dynamic, YouGov reports that support and sympathy for Israel among Western Europeans have reached the lowest levels the firm has recorded in its nine years of polling. Israel's net-negatives are -44 in Germany, -48 in France, -54 in Denmark, -52 in Italy and -55 in Spain. In the United States, Pew Research in March reported that Americans' support of Israel was the lowest in its 25 years of tracking that sentiment.  

https://www.zerohedge.com/geopolitical/israeli-ultra-orthodox-push-dissolve-parliament-force-election-over-conscription

Coal Is The New Bridge Fuel

 by Bernard L. Weinstein via RealClear Energy,

Once again, the consensus of government and private weather forecasters is that this coming summer will witness above-average temperatures in most parts of the United States. Already, warnings have been sounded that America’s power grids will be under great stress—as has been the case for a number of years—with a strong probability of blackouts and brownouts in some parts of the country.  For example, the North American Electric Reliability Corporation’s (NERC) summer reliability assessment published on May 18 cited the 15-state Midcontinent Independent System Operator (MISO) as the regional grid most likely to see a meltdown this summer.

NERC’s warning proved to be prescient. On May 25, more than 100,000 customers in and around New Orleans lost power for most of the day when electricity demand exceeded supply, despite an emergency order from the Department of Energy several days earlier to keep a 1,560 megawatt coal plant in Michigan on-line that was slated for closure by the end of May. ERCOT, the Texas grid operator, has also warned of possible outages this summer due to potential low solar and wind energy availability during peak demand. 

The strains on America’s power grids are easy to explain. After remaining relatively flat for a decade, electricity demand is now projected to jump 50% over the next 10 years. Investments in server farms, artificial intelligence, crypto-mining, and a revival of manufacturing activity account for most of this growth. For example, a recent study by the Berkeley National Laboratory found that data centers consumed 4% of total U.S. electricity in 2023 but will account for 12% of power demand by 2028.    

At the same time, construction of new base-load power plants—natural gas, nuclear, and coal—has plummeted. Driven by federal, state, and local tax incentives, wind and solar have accounted for the lion’s share of new installed generation in recent years. The problem, of course, is that these power sources are intermittent, which is why New Orleans lost electricity in May and why the Iberian Peninsula suffered a blackout in April.

Although several states—most notably Texas—have adopted programs to encourage new construction of natural gas plants, for the near term it’s critical to keep the nation’s remaining coal plants online.

Since 2010, 300 “always on” coal-fired power plants have been closed, reducing its share of generation from 45% to 16% nationwide. Only about 200 remain on the regional grids today.

The Trump administration has taken several steps to enhance power grid reliability and resiliency by keeping these coal plants on-line, including a series of executive orders signed by the President in early April. One of these orders allows a number of aging coal plants slated for closure to continue producing power. 

Not surprisingly, these actions have energized environmentalists who remain committed to shuttering the remaining coal fleet and banning the construction of any new fossil fuel power plants. But the renewables-or-nothing approach they favor is crashing into a new energy reality. Not only is power demand poised to surge but building and connecting wind and solar plants, as well as the infrastructure needed to integrate them into the grid, is proving increasingly costly and challenging. Coupled with higher interest rates and supply chain challenges, local opposition to wind and solar farms, as well as new transmission lines, is having a significant impact on the speed and scale at which new generation is entering service.

The era of tearing down existing, well-operating power plants before reliable replacement capacity is built and connected to the grid is over. The on-demand power plants already in service are more valuable than ever. While coal’s long-term future remains in question, its near-term importance is clear. Our existing fleet of coal plants can help us manage the transition to a more reliable and resilient energy future as we build the next generation of base-load resources.

Bernard L. Weinstein is retired associate director of the Maguire Energy Institute at Southern Methodist University, professor emeritus of applied economics at the University of North Texas, and a fellow of Goodenough College, London. 

https://www.zerohedge.com/energy/coal-new-bridge-fuel

Palantir’s Government Work on Data Collection Sparks New Privacy Fears

 Palantir PLTR -6.12% ▼ CEO Alex Karp pushed back against claims made in a recent New York Times article, which alleged that the AI software company had been involved in creating a database of personal information on Americans for the Trump administration. Speaking on CNBC, Karp firmly denied the accusation and stated that Palantir does not surveil American citizens. This interview comes after the company called the article “blatantly untrue” in an X post on June 3, where Palantir also went on to emphasize the strong security controls of its Foundry platform

https://www.tipranks.com/news/palantir-pltr-ceo-pushed-back-against-data-collection-report

'Bayer raised to Buy at Goldman after hitting bottom of negative earnings revision cycle'

 Bayer (OTCPK:BAYRY) (OTCPK:BAYZF) settled +4.4% in Frankfurt trading Thursday as Goldman Sachs upgraded shares to Buy from neutral with a €33 price target, raised from €29.10 previously, saying the stock's risk/reward into H2 2025 looks positive and catalysts including upcoming litigation newsflow could support a re-rating over the medium term.

Bayer (OTCPK:BAYRY) (OTCPK:BAYZF) may have reached the bottom of the negative earnings revision cycle following a strong operational start to the year, Goldman's James Quigley said, underpinned by strong momentum in its pharmaceutical business and disciplined cost-cutting action in its crop science business.

Regarding Roundup litigation, Quigley suggested a potential 20%-25% upside to current levels if the U.S. Supreme Court accepts the Durnell case, with relatively limited downside risk if the case is not accepted.

Quigley said he foresees positive consensus revisions as the market acknowledges the reset in Bayer's (OTCPK:BAYRY) (OTCPK:BAYZF) cost base due to a new operating model and the strong underlying performance, moving EBITDA estimates 2%-8% ahead of consensus across 2027-30.

https://www.msn.com/en-us/money/topstocks/bayer-raised-to-buy-at-goldman-after-hitting-bottom-of-negative-earnings-revision-cycle/ar-AA1Ga1EU