This week's Biotech Scorecard newsletter:
Six drugmakers, six months: Charting the FDA’s course in the post-Prasad era
$REPL Pierre Fabre $ATRA$QURE$CAPR$RGNX
https://t.co/sGa7G6YTDn
Let's look at how the FDA is treating $SRPT and $QURE differently.
The FDA grants accelerated approval to Amondys and Vyondys to treat Duchenne muscular dystrophy. Sarepta conducts a post-marketing confirmatory study that fails to show a benefit for either drug.
There is no evidence that patients are benefiting from either drug, based the outcome of a randomized, controlled study. Still, Sarepta pushes forward, seeking to convert accelerated approval to final approval. The FDA allows Sarepta to submit an application.
"The adequacy of the data to support conversion to traditional approval will be a matter of review," the FDA concludes, according to Sarepta.
Amondys and Vyondys should be withdrawn from the market. My opinion. I've said that repeatedly. There's a process, of course, so FDA should review the data. That's what regulators are supposed to do.
And then, there's UniQure and AMT-130, its treatment for Huntington's disease....
The FDA won't even allow UniQure to submit an application for accelerated approval. Bar the door, the FDA says, not even a review.
https://t.co/CmDs13aVry
New from me on $QURE and FDA. Free, no paywall.
The FDA, urged to avoid controversy, creates a new headache with attack against UniQure
Anonymous diatribe from a senior official plunges agency back into headlines
https://t.co/ceDE0TXjdI
Some context for the UniQure $QURE post below:
Earlier today, the FDA held a media call with the same "senior FDA official" who spoke to me (and other reporters) individually earlier in the week.
The call was set up obstensibly so that this senior FDA official could rail against UniQure without going on the record. He did exactly this for 30 minutes, repeating the same criticisms, claiming Uniqure's Huntington’s therapy is a failure, the sham surgery would be blinded even if just small "nicks" in the skin were made in a 30-minute procedure, dismissing the idea of formally reviewing the therapy, disregarding outside scientific experts, and then accusing the media of not adequately covering what the FDA (and this official) have been doing.
Reporters from Bloomberg, STAT, NY Times, WSJ, Politico and other media organizations were on the call.
@anish_koka The UniQure $QURE CEO is on the record, the "senior FDA official" is not. The interview with the "senior FDA official" was facilitated through official HHS/FDA channels on the condition that this person not be identified. That was their demand, not mine.
You think UniQure is lying about the sham surgery?
Surrogate endpoints are used routinely as the basis for accelerated approval.
cUHDRS, the disease-progression endpoint used to assess AMT-130 in the study, is not a biomarker.
You're way off base in accusing me of trying to churn false outrage.
You tweet. I do the actual reporting work.
Plus... Deeper cuts from my reporting this week. You asked some very thoughtful questions about the $QURE FDA situation. I responded...
Including: What is "sham surgery" in the context of a Huntington's study? UniQure and the FDA have stridently opposite views. Last night, I saw the HHS spokesman accusing UniQure of lying about sham surgery. That's inflammatory.
More here:
https://t.co/yGGcwqiXbE
In this week's Biotech Scorecard newsletter: The extremism of the FDA’s Peter Marks and Vinay Prasad has come with costs
Two regulators, two extreme regulatory philosophies, one replacing the other. The rare disease community is suffering whiplash. Drugmakers ( $QURE most recently) are frustrated. Investors are sitting on their wallets.
Adding to the confusion: The current FDA leadership often talks like Marks, but acts like Prasad.
https://t.co/yGGcwqiXbE
Read more on $QURE and FDA from me here:
FDA is ‘not convinced’ UniQure’s Huntington’s therapy has benefit, senior official says
Company accuses agency of reversal but hopes to settle on parameters of a new trial
https://t.co/YVIUYiaCMz
New reporting from me taking you inside the $QURE - FDA Huntington's gene therapy imbroglio.
I spoke to a senior FDA official late yesterday, who told me agency reviewers "are not convinced there’s any therapeutic benefit of the product. If we felt there was any therapeutic benefit, we, of course, would approve it. But they’re not persuaded."
I also spoke last night w/ UniQure CEO Matt Kapusta. The company was “incredulous that a senior FDA official is speaking to the media and communicating things that in many respects, have never been communicated to us."
“We’ve had five meetings with the FDA in the last 15 months, and a number of the things that were stated [by the FDA official] are borderline confidential information, and were never communicated to UniQure in any of the written feedback or otherwise. It’s highly concerning to us,” Kapusta added.
Kapusta also shared some interesting details about when, exactly, it received the minutes from its FDA meeting, and he addressed FDA Commissioner Makary's comments Friday on CNBC.
Lots more details in the story... Link in post below.
$QURE drops 45% after earnings.
That painful 45% drop makes sense given the severe regulatory roadblocks just announced. The biggest blow is the FDA rejecting early approval for their Huntington's therapy. The agency now demands a time-consuming trial where some patients receive a fake surgery as a placebo, pushing potential approval years away.
Adding to the pain, their Fabry disease and ALS treatments are both paused due to safety concerns like liver toxicity. The only silver linings are an advancing epilepsy program and a massive $622.5 million cash pile. Thankfully, this money secures their operations until late 2029.
$QURE AMT-130 update: Still blocked
The FDA stated that it cannot agree that data from the Phase I/II studies, compared to an external control, are sufficient to provide the primary evidence of effectiveness required to support a marketing application for AMT-130. The FDA strongly recommended uniQure conduct a prospective, randomized, double-blind, sham surgery-controlled study. uniQure intends to continue engaging with the FDA regarding Phase III development considerations and plans to request a Type B meeting in the second quarter of 2026 to further discuss potential study design approaches.
$QURE surged 375% last September after releasing highly anticipated topline data for AMT-130, its lead gene therapy candidate for Huntington's disease. The phase I/II study results were remarkable, showing that the hig-dose cohort experienced a statistically significant 75% slowing of disease progression at 36 months.
Now, the stock is back at it's original levels due to a regulatory update. The FDA abruptly reversed its previous guidance. The agency stated that the Phase I/II clinical data, was no longer considered sufficient to support a marketing application.
As they report earnings today, investors will watch for FDA Type A meeting updates on AMT-130 and Commissioner Makary's regulatory impact. Beyond Huntington's, they will assess their cash runway, defense against securities litigation, and Fabry pipeline progress.
EPS est. (0.93)
Rev est. ($5.75)
(Hopefully) Final word today on the Makary $QURE (or was it $RGNX) thing:
Bottom line: Makary shouldn't be talking publicly about unresolved drug applications. Uniqure doesn't even have an application submitted; and RegenxBio's CRL letter isn't posted to the FDA's web site.
Also, does Makary even know what the hell he's talking about?
"...there was a product where the researchers drilled a burr hole, literally a hole in people's skulls..." That's Uniqure, clearly. But...
"...inject intrathecally into the ventricle..." could be RegenxBio, which is injected into the spine.
Is Makary conflating two different therapies?
Total shitshow...
$QURE down this morning on comments made by FDA Commissioner Marty Makary to CNBC's Becky Quick.
In a discussion about rare-disease drug approvals and Vinay Prasad, Makary said this:
"I think there has been a bit of an effort to find a boogeyman to account for certain products that were not approved. For example, there was a product where the researchers drilled a burr hole, literally hole in people's skulls to interact inject intrathecally into the ventricle, a therapy the randomized control trial. At the end of the randomization period, it's found no benefit, and yet, this is one of the drugs that we were pressured to approve. Now, look, I have a lot of sympathy for those patients. There's nothing out there to offer them, but we're not going to go ahead and approve something like that that has morbidity associated with it."
This week's Biotech Scorecard newsletter: The old Vinay Prasad never left. He just changed jobs
Submissions to the FDA are handled by teams of reviewers, of course. But when I look across all of these recent cases, I see a consistent throwback to the old Prasad — questioning the legitimacy of biomarkers, surrogate endpoints, and single-arm clinical trials, even in the setting of rare diseases.
In some of these rare-disease drug rejections, Atara $ATRA and Regenxbio $RGNX are good examples, Prasad or the staffers he directs aren’t following the agency’s own guidance. Companies are told early that their clinical development programs meet FDA requirements, but then, almost arbitrarily, the FDA changes the rules.
Uniqure $QURE and its gene therapy for Huntington’s disease have been in a holding pattern for months because guidance it received long ago from the FDA is now, under Prasad’s watch, null and void.
Read more at link below...
On this week's Readout LOUD podcast: We chatted withLauren Holder @laurencurehd about $QURE AMT-130 and the FDA. Lauren is a Huntington's disease patient advocate and is, herself, living with the disease.
This interview is well worth your time. The Readout LOUD is available for streaming on all podcast platforms.
https://t.co/3JDu5L5itU
$QURE FDA update:
In the final meeting minutes, and consistent with uniQure’s November 3, 2025 press release, the FDA conveyed that data submitted from the Phase I/II studies of AMT-130 are currently unlikely to provide the primary evidence to support a BLA submission. uniQure is carefully evaluating the feedback and plans to urgently request a follow-up meeting with the FDA to take place in the first quarter of 2026.
In this week's Biotech Scorecard:
-- $QURE CEO Matt Kapusta dined privately with investors on Tuesday night -- and said some stuff, according to two attendees who filled me in.
-- A preview of $AGIO Pyrukynd Ph3 study in sickle cell disease. The readout is coming in December.
The FDA’s Vinay Prasad wrote today’s “plausible mechanism” paper offering a regulatory roadmap for personalized therapies.
Prasad is also refusing to allow $QURE to seek approval for a gene therapy to treat Huntington’s disease.
Does this make sense?
$QURE Q&A largely uneventful
Mgmt confirmed FDA guidance from Nov. 2024 meeting was study data+ECA supported a BLA filing.
Doesn't expect new mtg meetings to change FDA shift, but hope it outlines concerns in more detail and how to address.
"100% committed" to work with FDA to determine a path forward for an expedited BLA filing.
Stifel's Paul Matteis: Did you ask FDA why they changed their mind? What did they say?
Kapusta: Not going to comment on the details of the meeting.
$QURE call -- opening remarks from CEO Matt Kapusta:
The FDA's shift on AMT-130 data was "surprising, " "disappointing" and a "notable shift" from multiple meetings over the past year.
AMT-130 is an example of the "transformative innovation that the FDA has pledged to support."
Kapusta sounded like he was speaking to Makary, RFK Jr., trying to isolate Prasad.
@Ssunten_ I don't know you, but based on your X timeline, you are extremely devoted to $QURE. I'm sure the company appreciates your support. Good luck.
@Ssunten_ I appreciate you reading the article. It was a fair and balanced take on the current $QURE situation, based on what we know now. The assumption that this is entirely the fault of the FDA, when we don't have a full picture of the AMT-130 data, is a mistake.
I didn't interview Matt this week bc he declined my offer. I interviewed him in September when the data were announced and we hosted him on our podcast that week.
You may disagree with the critical viewpoint of the HD doc I mentioned in today's story, but to dismiss his comments bc you think he's being paid off is ridiculous and overly emotional.
This week's Biotech Scorecard newsletter: The FDA is a mess, but don't blame it for everything
I write about $QURE and $BHVN
Re: Uniqure and its gene therapy for Huntington's disease, the dissonance between the FDA's words and actions can be confusing.
Approving AMT-130 seems like a no-brainer win for the FDA and the policy initiatives pushed by its leadership.
The reversal certainly has Prasad's conservative data-stickler fingerprints all over it, BUT...
You have to consider the possibility that there is a significant issue with the AMT-130 data, the composition of the external control group, or both, that Uniqure hasn’t disclosed.
Slingshot Insights hosted a call Tuesday with an HD physician who was critical of the AMT-130 data, saying the therapy was "far from ready for approval."
$BHVN approval was a coin flip at best, so the CRL and the reasons for it are not really a surprise. $QURE is different in some ways.
This is what I wrote on Oct. 9
We should learn something about regulatory flexibility under the current FDA leadership when the agency renders a decision in mid-November on Biohaven Pharmaceuticals’ treatment for spinocerebellar ataxia (SCA), a rare and debilitating neurodegenerative disease.
“This is a really tough call. I’d say approval is a 50-50 shot, at best,” a Biohaven shareholder told me. I heard the same toss-up sentiment from other shareholders as well, reflecting uncertainty that seems to precede so many FDA decisions these days, exacerbated by Biohaven’s controversial data package.
In May, the FDA extended the decision date for the Biohaven drug, called troriluzole, by three months in order to review “recent submissions related to information requests from the FDA,” the company said.
Then in August, the FDA told Biohaven that a previously planned (but not yet scheduled) advisory committee meeting to review troriluzole was “no longer needed for regulatory decision making.”
Canceling an advisory committee meeting is often a negative indicator, as we saw recently with Capricor Therapeutics and its cell therapy for Duchenne muscular dystrophy. But troriluzole was submitted to the FDA’s Center for Drug Evaluation and Research, or CDER. Its leader, George Tidmarsh, has said publicly that advisory committee meetings are often unnecessary and their use should be reduced, agency wide.
Under the CDER umbrella, troriluzole is being reviewed by the Division of Neurology I within the Office of Neuroscience — a group that has a history of approving drugs with messy data, like Aduhelm and Skyclarys. It’s also been stable, personnel-wise, even with all the FDA staff turnover.
When it comes to drugs for rare diseases, clinical data may not matter as much as they do in other cases, as we saw recently with the approval of a drug for Barth syndrome for Stealth BioTherapeutics. In that case, a decision made by FDA review staff to reject the drug was overturned by a senior agency leader.
I wrote about troriluzole in this newsletter in September 2024, making the point that its data package was going to test the agency’s appetite for regulatory flexibility.
Biohaven’s submission is supported by a Phase 3 study in which troriluzole delayed the progression of SCA by 50% after three years, representing a 1.5-year treatment gain. The comparator arm in this “real world” study was not a placebo, but a carefully selected group of untreated SCA patients enrolled in an external, natural history study of the disease.
The study results were announced in September 2024, and at that time, Biohaven said it had worked with the FDA on the design of the study to ensure that the external control patients closely matched those in the treatment arm, bolstering the validity of the results.
Drug companies commonly assure us that the FDA is on board with whatever they’re doing. The truth is often something different. The troriluzole situation is muddled further because the FDA is now run by officials with very different perspectives than their predecessors.
One more wrinkle: Before it had real-world comparison data, Biohaven ran a true, placebo-controlled study. It failed. The company submitted for approval anyway, and the FDA turned away the application without review.
Biohaven hasn’t disclosed a specific FDA decision date, but it should come the week of Nov. 10, based on previous disclosures.
$QURE$BHVN The question I (we) now struggle to understand:
Is the "new" FDA now uniformly opposed to using external /historical controls in drug applications?
Or
Were there significant / insurmountable flaws in these specific uses of ECs that led to the FDA decisions?
@basadomente I'd like to speak to $QURE simply because I prefer to hear from them directly, and not filtered through analyst notes. Not asking for preferential treatment, simply the same access they give analysts and investors.
We hosted CEO Matt Kapusta on our podcast after the HD data were reported. He was great. I want to talk to him when the news is not so great, too.
$QURE has been talking to analysts and investors all day. The company declined to speak to me.
Here's what mgmt is apparently saying about the FDA, per Cantor's Kristen Kluska https://t.co/X9IsNSu5JY
@Biohazard3737 $QURE You may have already mentioned this theory, but at the risk of repeating, I wonder if today's FDA guidance (or pulling the old) is an effort to be more helpful than hurtful?
ie FDA says to QURE - "there is an issue, let's try to resolve it BEFORE you file, rather than after, when we would have to reject you."
Uniqure’s $QURE FDA submission for its Huntington’s disease therapy thrown into question https://t.co/tfZxYM9iKL via @DrewQJoseph
12 hours of head-spinning FDA news....
On $QURE: I wrote this in my Sept. 25 newsletter:
"Bear in mind: What we have seen so far of the AMT-130 data are mentioned in a Uniqure press release. Fairly detailed, yes, but it will be important to see the data fully presented at a future medical meeting and published in a peer-reviewed journal.
The validity of external control arms like the one used by Uniqure is still hotly debated, even as regulators, including the Food and Drug Administration, allow them under certain circumstances. It’s been lost to memory, but recall that the AMT-130 study started with a true, sham-surgery control arm that showed no benefit for the gene therapy. It was only after the company reconfigured the study and started using natural history comparators was a benefit observed."
To be clear: I was also very positive on the data and its regulatory stance at the time. I thought this was a gene therapy that would be approved, even with Vinay in charge.
That looks wrong now, unless we see another pivot a la $REPL.
@avidresearch I don't know anything about the $BHVN external control or how it was constructed, so I can't comment. $QURE is sourcing its ECA from a very large, independent and well-regarded natural history study, which works in its favor, I think. Legit, even if doesn't entirely eliminate the risks.
On the other side of the spectrum, toally illegitimate, for instance, you have a company like $NWBO that made up its own ECA AFTER knowing its drug failed and then cherry-picked studies to fake a positive result. Pure garbage.
ECAs remain controversial. Hopefully we learn something from $BHVN and $QURE.
Uniqure $QURE and its Huntington’s therapy win the week in biotech. Plus: Why Stoke Therapeutics’ $STOK quiet move higher makes sense
https://t.co/C3VnHKtTX2
This week's Biotech scorecard newsletter: (Almost) 100% positive vibes
1. $QURE, of course.
The 75% slowing of disease progression reported by Uniqure with its Huntington’s disease gene therapy AMT-130 was the kind of stop-reading-and-gasp moment that crystalizes the profound impact these types of one-time treatments can have for patients dealing with rare diseases.
But, bear in mind...
The validity of external control arms like the one used by Uniqure is still hotly debated, even as regulators, including the FDA, allow them under certain circumstances. It’s been lost to memory, but recall that the AMT-130 study started with a true, sham-surgery control arm that showed no benefit for the gene therapy. It was only after the company reconfigured the study and started using natural history comparators was a benefit observed.
Also:
-- Why $STOK 's quiet move higher makes sense. The stock is up almost four-fold from its April low and has doubled year to date. Why? I asked around...
-- $ACAD was a "clearing event" for $SLNO. Next up, earnings. What's the whisper number for Vykat sales?
Newsletter link below...
$CLPT higher on $QURE results. ClearPoint sells the imaging equipment that allows the precise surgical implantation of the gene therapy into the brain.
$QURE Also AMT-130 showed stat sig 60% disease slowing on TFC, assesses patients’ ability to work, drive and perform other functions of daily life. NfL also lower.
Gene therapy isn't for everyone, but these results are a big win.
Story here: https://t.co/XByXgHDZeF
BREAKING: $QURE experimental gene therapy for Huntington’s slowed disease progression by 75% after three years, study shows.
Very strong results. FDA filing in Q1 '26. My story link in next post.
“These data suggest the potential for a disease-modifying drug,” Rachel Harding, a Huntington’s researcher and assistant professor at the University of Toronto, told me.
She addded, “We haven’t seen any other drug do anything close to this yet. This is something that the Huntington’s community have been chasing for a really long time.”
