Biogen’s Qalsody won FDA approval in 2023 to treat a rare, genetic form of amyotrophic lateral sclerosis. On Tuesday, QurAlis presented interim Phase 2 data showing the potential of a similar drug to more broadly treat the neurodegenerative disease.
The next round of amyotrophic lateral sclerosis candidates is starting to yield results, and while mid-stage data reported by Corcept Therapeutics last week were mixed, results announced Tuesday by QurAlis indicate a dramatic slowing of the cruel neurodegenerative disease.
In a Phase 2 study of 69 patients with ALS, QurAlis’ antisense oligonucleotide (ASO) elicited up to a 50% decrease in disease progression, an interim analysis presented Tuesday at Target ALS’s annual meeting showed.
Additionally, the biotech reported cerebrospinal fluid (CSF) reductions in both phosphorylated neurofilament heavy chain (pNfH) and levels of neurofilament light chain (NfL), two markers of axonal damage in ALS.
The FDA has concluded that CSF pNfH predicts ALS disease progression, QurAlis CEO Kasper Roet told BioSpace prior to his presentation.
QurAlis’ lead asset, QRL-201 is a first-in-class antisense drug intended to restore stathmin-2 expression in patients with ALS, according to the company’s website. Encoded by the STMN2 gene, stathmin-2 is well-known for neural repair and axonal stability and is downregulated in nearly all people with ALS. “[CSF pNfH] is also directly tied to stathmin-2 loss,” Roet added.
He explained that stathmin-2 is the most downregulated protein in sporadic ALS, so it was a logical target. “We think that is the path toward success, and we think that our trial results are really also validating that strategy.”
And the April 2023 FDA approval of Biogen and Ionis’ Qalsody for patients whose disease is associated with a mutation in the superoxide dismutase 1 (SOD1) gene was an additional confirmation of the strategy, he added. “[It] was the first real validation [of] a genetic medicine having a transformative effect on the disease.”
QurAlis’ own data now further support Roet’s belief that a genetic approach “is the only way to really be successful in this disease.” The Anqur trial showed “clear evidence of target engagement,” according to QurAlis’ presentation, with STMN2 levels at least doubling. And the 10-mg dose of QRL-201 led to the 50% decrease in progression at day 253, as measured on the Revised ALS Functional Rating Scale (ALSFRS-R).
While myriad ALS researchers have pointed out apparent flaws with the ALSFRS-R scale—notably a lack of sensitivity at the bottom of the scale—it remains the gold standard for prospective ALS therapies and is a registrational endpoint that will be required for full approval of QRL-201, Manoj Malhotra, chief medical officer at QurAlis, told BioSpace in the same interview.
QRL-201’s effect was more apparent during the trial’s six-month washout phase than during the three months of treatment, not surprising for an ASO, Roet said. These drugs “have a pretty long half-life, and ALS’ effects on function seem to have a delayed effect,” he explained, pointing to Qalsody as another example. That ASO missed the primary endpoint in the Phase 3 Valor study—a statistically significant change from baseline to week 28 on the ALSFRS-R—but Biogen ultimately won accelerated FDA approval of the drug based on its effect on NfL.
QurAlis is gearing up to begin a Phase 3 study of QRL-201 in the first quarter of 2027, Malhotra said. This trial is expected to include about 270 patients.
The biotech, which launched in 2018, has an early- to mid-stage pipeline that also consists of a Kv7.2/7.3 ion channel opener in Phase 1 development for hyperexcitability-induced disease progression in ALS. It is also in early-stage trials for epilepsy and pain. QurAlis has partnered with Eli Lilly on QRL-204, a splice-switching ASO designed to restore the function of neuronal communication protein UNC13A in people with ALS and frontotemporal dementia.
An ALS therapeutic comeback?
These data provide a glimmer of light in the darkness for the ALS community, which has been inundated by setbacks the past couple of years, highlighted by the market withdrawal of Amylyx’s Relyvrio and the failure of candidates from Sanofi and Denali Therapeutics.
A handful of other biotechs are also working to bring new options to patients with ALS. Last week, Corcept Therapeutics reported two-year overall survival data from a Phase 2 trial of dazucorilant. While the selective cortisol modulator missed the trial’s primary endpoint, showing no significant effect on motor skills and other functional criteria after 24 weeks of treatment, Corcept did detect a survival signal. After two years, patients on 300 mg of dazucorilant saw an 87% reduction in risk of death when compared with those who received a placebo.
Corcept is preparing to move dazucorilant into a Phase 3 study later this year, Bill Guyer, the biotech’s chief development officer, said in a prepared statement on April 30.
Meanwhile, Amylyx is attempting a comeback with AMX0114, an ASO targeting Calpain-2, which, according to a 2024 presentation by the biotech, is implicated in axonal degeneration. Calpain-2 levels are elevated in patients with ALS, and its inhibition has shown benefit in a mouse model of the disease, Amylyx states in the deck. Biomarker data from the Phase 1 Lumina study are due in the first half of this year, Mizuho analysts said in an April 29 note to investors.
The earlier-stage pipeline is also healthy. Nearly a third of companies that BioSpace interviewed at BIO2025 highlighted ALS as a key focus. And Trace Neuroscience, a member of BioSpace’s NextGen: Class of 2026, is operating in a similar arena to Biogen and QurAlis. The biotech, which launched in November 2024 with $101 million in series A funds, is developing an ASO that restores UNC13A protein to preserve and potentially improve muscle function in patients with ALS. The program is set to enter the clinic around the middle of this year, a company spokesperson told BioSpace in an email.
Roet, for one, is hopeful. “We know that if you have a genetic target, a genetic medicine, a precision medicine approach, that you can really do something meaningful for patients.”
