Newsletter · · Ashutosh Agarwal

Gene Therapy's Durability Problem as uniQure's 75% Becomes 44% - Biotech Pipeline: Gene/Cell, Neuro & Tools - Week of October 4, 2026

Biotech Pipeline: Gene/Cell, Neuro & Tools for the week of October 4, 2026. Podcast synthesis on uniQure's Huntington's gene therapy fading from 75% to 44% slowing at four years, Beam's trade-secret lawsuit over a China spinout, strong and risky CAR-T results in AL amyloidosis and autoimmune disease, AbbVie's tavapadon Parkinson's approval, and the GLOBE pricing rule that now covers only about four companies.

Biotech Pipeline: Gene/Cell, Neuro & Tools

Week of October 4, 2026: Gene Therapy's Durability Problem as uniQure's 75% Becomes 44%

Last week the gene-therapy argument was all about money: if a one-time cure works, who pays? This week brought the question that should come first: how long does "one-time" actually last? uniQure's Huntington's disease gene therapy, one of the most closely watched programs in neurology, came back with four-year results showing its benefit had shrunk by almost half. The stock fell 37% in a day. Yet the FDA is still willing to consider approving it, and at least one patient advocate says she'd take it tomorrow.

Around that story: a lawsuit that puts US–China biotech rivalry in a courtroom, a remarkable CAR-T result in a rare blood disorder, a split verdict on CAR-T for autoimmune disease, a long-delayed payoff for AbbVie's $8.7 billion neuroscience bet, and a Medicare drug-pricing experiment that has shrunk to almost nothing. The large life-science tools companies were absent from the podcasts again.

TL;DR

  • uniQure's Huntington's gene therapy fades, but it isn't finished. The therapy slowed disease progression by 75% at three years. At four years that figure is 44%, and it's no longer statistically significant. The stock fell 37%. The FDA has still agreed to review it on the three-year data, with a decision likely in early or mid-2027. (The Readout Loud, Oct 1; Biotech Hangout, Oct 2; BioSpace, Sep 30)
  • Beam Therapeutics sues over a China spinout. Beam alleges that a former scientist took its trade secrets to found a Chinese company, Yoltec, which then licensed technology to a new, US venture-backed rival. STAT's Adam Feuerstein called it his "favorite story of the week." (The Readout Loud, Oct 1)
  • Cell therapy had a strong week, with one big caveat. Immix Biopharma's CAR-T cleared the disease in 89% of 45 patients with AL amyloidosis. A CAR-T for stiff person syndrome showed clean safety at one year. But Novartis has reported three deaths in its autoimmune CAR-T trials. (Biotech Hangout, Oct 2; BioSpace, Sep 30)

What's new

1. uniQure: what happens when a "one-and-done" therapy starts to wear off

Some background first. Huntington's disease is an inherited brain disorder that steadily destroys movement, thinking and mood, and it is fatal. No approved drug slows it down. uniQure's therapy, AMT-130, delivers a gene into the brain with a modified, harmless virus. The goal is to lower production of the faulty protein that drives the disease.

A year ago the results looked extraordinary. On The Readout Loud, STAT's Adam Feuerstein recapped them: at three years of follow-up in 12 patients, the therapy "slowed the progression of Huntington's by 75% compared to patients from a natural history study." A natural history study is a database of untreated patients, used here as the comparison group because there was no placebo arm. That result was "both clinically meaningful and statistically significant." (The Readout Loud, Oct 1)

This week's four-year update was weaker. The therapy now "slowed disease progression by 44%, and the benefit was no longer" statistically significant. Feuerstein put it in context: "We've seen this with other gene therapies where, over time, the efficacy of the gene therapies wanes." But he didn't dismiss the result: "Even at four years, 44%, that's still a very meaningful slowing of disease progression for a disease like Huntington's, where you see patients progress three, four years, and often patients die at that time point." (The Readout Loud, Oct 1)

The market was harsher. On Biotech Hangout, the panel noted the stock "fell 37%" on the day of the news and slipped about 5% more afterward. They called it a "pretty big diminution in the efficacy." (Biotech Hangout, Oct 2)

The company's defence. On the BioSpace podcast, senior editor Heather McKenzie explained management's argument. They called the data "unprecedented," because "there is really nothing else disease modifying for Huntington's on the market." They also blamed the comparison group. The updated version of the natural-history database (called Enroll-HD) "includes more patients, but also a higher rate of missing data," which, executives argued, "underestimated disease progression." In other words, they say untreated patients probably declined faster than the database shows, so the true benefit of the drug is understated. BioSpace managing editor Jeff Axt noted that comparisons against outside control groups remain a sore point with the FDA. (BioSpace, Sep 30)

The regulatory twist. This is where FDA leadership changes matter. According to Feuerstein, the FDA's previous leadership, under Vinay Prasad, had rejected uniQure's plan to rely on the natural-history comparison. Under the new leadership, "the company and the FDA have now reached an agreement where, indeed, they will consider this gene therapy for approval based on the three-year data." (The Readout Loud, Oct 1) uniQure filed its application last month and asked for priority review, a faster six-month review track (Biotech Hangout, Oct 2). BioSpace said the FDA's decision on whether to accept the filing is expected in the fourth quarter. If it is accepted, an approval decision is likely in "early or mid-2027." (BioSpace, Sep 30)

The patient view. Feuerstein spoke with Huntington's patient advocate Lauren Holder, who said the new data "absolutely not" changed her mind:

"If these four-year data were the only data that I ever saw, I would still want to get this gene therapy. This is something that I would want for me. This is something that I would want for other patients with Huntington's."

Why it matters beyond uniQure. Brian Skorney on Biotech Hangout gave the broader verdict on gene therapy: "It's a very complicated thing to get a construct that produces… protein in sufficient quantities to move the needle." Hemophilia B, a bleeding disorder, is the clear success story, because "if you need to make factor [IX] in blood, you can do it pretty easily." Elsewhere progress has been "slower than I expected… I thought we were going to have more of a renaissance earlier. And it's been harder, but science is a hard thing." Sam Fazeli of Bloomberg Intelligence added that venture investors remain "gung-ho" about solving the delivery problem, meaning how to get genes into the brain, even if big pharma's interest comes and goes. (Biotech Hangout, Oct 2)

2. Beam vs. Yoltec: the US–China biotech rivalry goes to court

Beam Therapeutics (BEAM) makes base editors, a more precise form of CRISPR that changes a single DNA letter without cutting both strands. Beam has sued, alleging that "one of its former scientists used its intellectual property when founding a Chinese biotech company" called Yoltec. STAT's Allison DeAngelis explained on The Readout Loud why this is more than a routine dispute: "That company, called Yoltec, made a licensing deal earlier this year with some venture capital firms, which actually led to the creation of a new U.S. company that's directly competing against Beam." (The Readout Loud, Oct 1)

The specifics alleged in the suit are pointed. According to DeAngelis, Beam says it reviewed its electronic records and found the employee "was going into their systems on weekends late at night, looking at things that weren't even related to her role and were what Beam considers trade secrets," before leaving to join the company that now competes with Beam. These are Beam's allegations, and none has been tested in court.

Feuerstein called it his "favorite story of the week" because "it just strikes to the heart of so much of what we've been talking about, you know, biotech innovation and competition against China and whether it's a level playing field." DeAngelis described a wider worry in the startup world that "scientists that are working with their companies will leave and go start companies in China, or that Chinese companies will find a way to infringe on their intellectual property and really decimate their efforts." (The Readout Loud, Oct 1)

Regular readers will recognize this as the darker side of a theme we've followed since our first issue in May: Western pharma licensing Chinese assets. The licensing flow is the commercial side of the story. This lawsuit is the legal and political one.

3. CAR-T's good week, and the safety question it can't escape

CAR-T therapy takes a patient's own immune cells (T cells), engineers them to hunt a specific target, and infuses them back. It transformed blood cancers. Now companies are pushing it into other diseases, and this week showed both the promise and the risk.

The standout result: AL amyloidosis. In this rare disorder, abnormal plasma cells in the bone marrow churn out a misfolded protein that builds up in and damages the heart and kidneys. On Biotech Hangout, Greg Sivanovich reported "truly spectacular" mid-stage data for Immix Biopharma's CAR-T, NXC201: an "89% overall complete response rate… in a trial of 45 patients." A complete response means no detectable disease. Standard treatments get complete responses in roughly "5% and 35%" of patients, depending on the setting. Sivanovich floated the possibility of a "98% complete response rate" by the final update in March 2027, as more patients deepen their responses. The disease affects "less than 50,000" people in the US and has "no approved therapies." Despite the data, the stock closed down about 10% because the company raised $125 million at the same time, and new shares dilute existing holders. (Biotech Hangout, Oct 2)

Autoimmune disease: clean in one trial, deadly in another. On BioSpace, McKenzie reported positive one-year data from Kyverna's CAR-T in 26 patients with stiff person syndrome. This rare autoimmune disorder causes severe muscle rigidity and spasms, and patients improved in "mobility and leg function." Just as important, there was no high-grade cytokine release syndrome (a dangerous immune overreaction), no high-grade neurotoxicity, and none of a rarer inflammatory complication. The contrast is stark. Axt noted that Novartis has had "three deaths in autoimmune trials" and "paused several other trials," attributed to a "life-threatening hyper-inflammatory syndrome," and that Bristol Myers Squibb "saw some safety signals" too. McKenzie said patients with conditions like lupus "would be willing to take" the risk, given that CAR-T has put some of these diseases into remission. But that may hold only for a "subset of patients" with severe disease, not the broad autoimmune market investors have imagined. (BioSpace, Sep 30)

The next frontier: in-body CAR-T. Today's CAR-T is made outside the body, one patient at a time, which is slow and expensive. "In vivo" CAR-T would instead engineer the T cells inside the patient. On Moving Medicine Forward, a podcast from contract research firm CTI Clinical Trials, Moya Daniels, head of regulatory at private Optieum Biotechnologies, said the company plans to file its first application to start human trials (an IND) "before the end of the year." The program is a conventional CAR-T for recurrent glioblastoma, an aggressive brain cancer. It targets a protein called FAP-alpha, which is "not highly expressed in normal adult tissues" but is abundant in the tumor and the tissue around it. Daniels also said the company is doing discovery work on in vivo CAR-T and will be "laser focused on an in vivo product," which could open diseases like rheumatoid arthritis, systemic sclerosis and fibrosis. It's a small private company, so read this as evidence of where early-stage money is heading, not as a data point. (Moving Medicine Forward, Oct 1)

4. AbbVie finally gets something back from its $8.7 billion Cerevel deal

In neurology, the FDA approved AbbVie's (ABBV) tavapadon for Parkinson's disease. On BioSpace, senior editor Gabrielle Mason called it "the first selective D1, D5 receptor agonist to become available in the U.S." In plain terms, it stimulates a different set of dopamine receptors than existing Parkinson's drugs, which mostly target the D2/D3 family. The label is broad. It covers "early and later stage of disease," used "with or without L-DOPA," the standard Parkinson's drug. The approval was based on the Phase 3 TEMPO program, and Mason, citing William Blair, put the annual cost at about $59,000. (BioSpace, Sep 30)

The backstory is what makes it interesting. The drug came with AbbVie's $8.7 billion acquisition of Cerevel Therapeutics in 2023 (Biotech Hangout rounded it to $9 billion). Cerevel's prize asset was meant to be emraclidine for schizophrenia, and it failed in trials less than a year after the deal closed. On Biotech Hangout, Sivanovich said tavapadon "was kind of lost in the shuffle of all the market excitement around the muscarinics" (the new class of schizophrenia drugs emraclidine belonged to), but that it represents at least partial value recovery. He called it "very welcome news for the Parkinson's community," while noting that the bigger unmet need remains "disease modifying therapies that address the root cause." (Biotech Hangout, Oct 2)

5. Medicare's international drug-pricing experiment shrinks to four companies, and Biogen is one of them

On Drug Fix, the Pink Sheet's regulatory podcast, senior writer Kathy Kelly explained the final version of GLOBE. This is a mandatory Medicare experiment that ties prices of physician-administered drugs (Medicare Part B) to what other wealthy countries pay. Companies that signed separate voluntary pricing deals with the administration, through a Medicaid program called GENEROUS, are excluded. So are orphan-only drugs, drugs facing generic or biosimilar competition, and drugs that already have Medicare-negotiated prices. The result: only about four manufacturers remain subject to it, including Biogen (BIIB), Takeda and Daiichi Sankyo, though Kelly said that "could change if these companies also finalize agreements with the administration." (Drug Fix, Oct 2)

The savings estimate collapsed with the scope. CMS had projected $11.9 billion in savings in the December proposal. The final rule projects $400 million over seven years. Executive editor Derek Ingerie asked the obvious question: "Can you really do a demo with four… participants?" Kelly flagged a loophole raised by health-policy scholar Rachel Sachs. The exclusion applies by manufacturer, not by drug, so companies can choose which drugs to put into the voluntary program and keep their most expensive products out of GLOBE. As Ingerie put it, "if you figure out a way to not have the most expensive drugs in the program, it kind of defeats the purpose." The rule is widely expected to face a legal challenge, partly because two key exclusions weren't in the original proposal. Kelly also suggested it may work mainly as leverage to push the remaining companies into voluntary deals. (Drug Fix, Oct 2)

For Biogen holders, the takeaway is that Biogen is one of the few companies still exposed to a Medicare price experiment. It also has an obvious way out: sign a voluntary deal.

The debate

Is a fading gene therapy still worth approving?

The case for: Huntington's has no disease-slowing treatment at all, and patients decline and often die within the time frame of this study. A 44% slowing at four years is, in Feuerstein's words, "still a very meaningful slowing." The company argues the comparison database understates how fast untreated patients decline, and the people who would actually receive the drug, represented by Holder, say they want it. The FDA's willingness to review it on the three-year data suggests the agency agrees, at least enough to look. (The Readout Loud, Oct 1; BioSpace, Sep 30)

The case against: The trial is small (12 patients at the top dose), has no placebo group, and the benefit is shrinking and no longer statistically significant. The company's explanation, that the comparison data got noisier, cuts both ways: if you can't trust the comparison group, you can't fully trust the 75% either. The 37% one-day drop shows investors marking down both the odds and the value of approval. And Skorney's broader point stands: outside hemophilia, gene therapies have repeatedly struggled to make enough protein for long enough. (Biotech Hangout, Oct 2)

Where it nets out: This connects directly to last week's payer debate. An ICER guest told us then that we are only now "starting to get" long-term data on how well these therapies hold up, and that's why payers want refunds if a therapy stops working. uniQure is the first big test of that worry in neurology. A $2–3 million one-time price is far easier to defend for a therapy whose benefit holds than for one whose benefit fades. Note that no uniQure executive spoke on a podcast this week; the company's case came to us through journalists.

Is CAR-T safe enough for autoimmune disease? Both sides showed up this week. Kyverna's clean one-year safety data in stiff person syndrome supports the bull case. Novartis's three deaths and trial pauses, plus BMS's signals, support the bear case. McKenzie's middle view seems right for now: the market is likely the sickest patients, at least until safer approaches like in-body CAR-T are proven. (BioSpace, Sep 30)

Names in play

  • Beam Therapeutics (BEAM). The lawsuit is a defensive move to protect its base-editing know-how. The risk is a well-funded, US venture-backed competitor built partly on technology Beam says is its own. Watch how the court handles the case and whether the rival company's backers respond. Note that the podcasts covered only Beam's allegations.
  • AbbVie (ABBV). Tavapadon gives AbbVie a differentiated Parkinson's drug with a broad label, and some redemption for the Cerevel deal. Sivanovich's caveat is that it treats symptoms rather than slowing the disease.
  • Biogen (BIIB). Biogen is one of roughly four companies still caught in Medicare's GLOBE pricing experiment, unless it signs a voluntary pricing deal. There was still no Leqembi launch data on the podcasts this week.
  • Regeneron (REGN), outside gene editing. Regeneron's muscle-preserving antibody trevogrumab, combined with semaglutide (Wegovy), showed patients keeping "more or less all of the muscle" on MRI scans in data presented at the EASD diabetes meeting. Skorney's doubt: "FDA probably isn't going to accept MRIs as a clinically validated endpoint," which raises the question of what endpoint would win approval. He also noted that Roche dropped its own myostatin program. (Biotech Hangout, Oct 2)

Read-throughs

The biotech market: strong year, painful quarter for crowded names. On Biotech Hangout, the panel said the XBI biotech index is up 27% this year, against 7% for the broad healthcare ETF, 13% for the S&P 500 and 17% for the Nasdaq. It peaked in late August at $169 and is down about 9% since. Eric Schmidt said the index was "essentially flat" in the third quarter but hid huge differences. Stocks few investors owned, or many had bet against, such as Moderna, Iovance and Summit, "propped up the index," while "companies that everyone owns are just getting hammered." There have been about 23 biotech IPOs so far this year, possibly 30-plus by year-end, with T-Rex Bio, Iambic and City Therapeutics in the queue. 2026 is also shaping up as a "banner year" for reverse mergers, where a private company goes public by merging into an existing listed shell. (Biotech Hangout, Oct 2)

Big pharma funding without buying. AstraZeneca is investing $2 billion in Summit Therapeutics in an all-stock deal to fund ivonescimab, a cancer antibody that blocks two targets (PD-1 and VEGF) and has "already snagged a couple of approvals in China." BioSpace senior editor Annalie Armstrong stressed that this is a share purchase, not a licensing deal: Summit keeps the drug. Summit had $690 million in cash as of July, about a year of runway; Stifel now sees two to four years. An FDA decision in a form of lung cancer (EGFR-mutated non-small cell lung cancer) is due on or before November 14. That's outside our core coverage, but it's a funding model worth watching for cash-hungry gene and cell therapy companies. (BioSpace, Sep 30)

FDA leadership: still in flux, especially for gene therapy. Drug Fix reported that the FDA has reopened its search for a permanent director of the Office of Therapeutic Products, the group within the biologics center that reviews cell and gene therapies. The new application window runs only to October 13, about half as long as the first, and the education requirement dropped from an MD or PhD with clinical experience to "bachelor's degree or higher in a related academic field." The FDA has also quietly made consumer representatives on advisory committees non-voting. (Drug Fix, Oct 2) On BioSpace, Axt noted that commissioner nominee Heidi Overton faced tough Senate questions over her support for an August executive order to split the combined MMR vaccine, and she has not yet been confirmed. (BioSpace, Sep 30) For gene-therapy sponsors like uniQure, the short-term picture is a more flexible agency, but with a leadership bench that is still being filled.

Competing approaches: gene silencing. Hard Drugs, an explainer podcast, made a useful contrast with gene editing. Instead of permanently changing DNA, siRNA drugs block a gene's instructions, and one dose lasts "weeks or months, or sometimes it's like half a year." There are now eight FDA-approved siRNA drugs, including inclisiran, which lowers LDL cholesterol by silencing PCSK9. That's the same target some in-body gene editors are going after with a one-time treatment. The hosts noted that Alnylam took "about 15, maybe 20 years" to get its first approval, then approvals came quickly. A recent Alnylam trial showed you can lower Alzheimer's-related APP biomarkers with a drug injected into the spinal fluid. But whether APP can be lowered in specific brain cells "is not something that has an affirmative answer yet." The hosts' main risk: not the technology, but that "we actually just got the theory wrong." (Hard Drugs, Oct 2) The read-through for cholesterol editing: a twice-a-year shot is the bar a one-time edit has to clear on price and safety.

Alzheimer's blood tests: a European expert backs them, with a math lesson. On a Keeping Current workshop, Prof. Charlotte Teunissen of Amsterdam UMC said blood levels of p-tau proteins rise "400% to 700%" in Alzheimer's. "That's really a large increase which allows the use in routine clinical practice." The p-tau217 test scores 0.92 to 0.96 on a standard accuracy scale where 1.0 is perfect. Then she showed why setting matters. With identical test performance, the share of positive results that are true positives is about 90% in a memory clinic, where half the patients have the disease, but only 69% in primary care, where about a fifth do. For now, the intended use is specialists seeing patients with measurable memory problems. She also flagged that kidney disease produces false-positive blood results, and spinal taps aren't advised for patients on blood thinners. For patients with both, "the only way of testing" is an amyloid PET scan. She also gave reassuring data on spinal taps: in 3,868 people across Europe, 9% reported the typical post-procedure headache. Her bigger point, which supports Leqembi and Kisunla: the anti-amyloid drugs' trials succeeded because "the patients that were included in the trial had a biological diagnosis." (Keeping Current, Sep 28) That's consistent with last week's US course: blood tests first, PET for hard cases.

Tau: new biology on how it spreads. On This Week in Neuroscience, University of Utah scientist Jason Shepherd described a new paper in Cell. It shows that a memory-related protein called Arc helps package toxic tau into tiny bubbles (vesicles) that carry it from one brain cell to the next. Without Arc, there were "very, very, very few" transfer events in mice, and vesicles from Arc-free brains showed "no seeding," meaning they didn't trigger new tau clumps. In human Alzheimer's brains, "whenever there was a high level of tau, there were also high levels of ARC in these vesicles." Shepherd's view: "Tau is actually the culprit that kills the cell in the end, not the amyloid." This is early, academic work, but it adds a possible new target to the tau-focused programs at Roche and others. (This Week in Neuroscience, Sep 29)

Bioprocessing: how "a fool's game" became the industry standard. The large tools companies were silent, but Smart Biotech Scientist offered useful history. John Bonham-Carter commercialized the ATF filter behind perfusion, a way of running bioreactors continuously so they produce much more. He sold his company, Refine, to Repligen in 2014, when Repligen was "tiny… like 60, 70 people." For years, he said, "nearly everyone was ignoring me, apart from Amgen." Today "almost everyone runs some kind of perfusion device," and Sartorius's "whole marketing campaign upstream" is built on intensifying processes this way. The economics: Amgen built "factories of the future" for $300–400 million against $1–2 billion for the same output, and a Biogen paper showed "30% extra throughput for no real change in a qualified process." Novartis, once adamant it would "never, ever run perfusion," went on to build "the largest single-use continuous facility in the world." (Smart Biotech Scientist, Sep 29) For Repligen and Sartorius, it's a reminder that their growth comes from manufacturing methods that took a decade to catch on and are now the default. It's history, though, not a read on current orders.

What changed

Durability moved from footnote to headline. Last week's argument assumed gene therapies work and asked who pays. This week, the most-watched neurology gene therapy showed what wearing off looks like in real data, and the market repriced it by more than a third in a day. Meanwhile, cell therapy's story split in two: excellent efficacy (Immix, Kyverna) on one side, real safety deaths (Novartis) on the other.

The FDA looks more flexible. A review that the previous leadership blocked is now going ahead. Paired with the reopened, lower-bar search for a cell and gene therapy chief, the regulatory direction looks more permissive, but less settled.