Opakalim

Xenon Pharmaceuticals’ lead drug greatly reduced the frequency of seizures in a Phase 3 epilepsy study, supporting the company’s plans to file for FDA approval in the third quarter. The drug, azetukalner, would be Xenon’s first commercial product since its founding in 1996. Wall Street analysts have high hopes for the oral treatment, forecasting over $1 billion in sales by 2031, according to estimates from Visible Alpha. Xenon’s stock $XENE soared more than 45% on Monday morning, valuing the 370-employee company at about $4.9 billion. High and low dose levels of azetukalner both beat a placebo group in reducing seizures, Xenon said in a statement Monday. The study randomized 380 volunteers with a common type of epilepsy known as focal onset seizures. The typical participant entered the study experiencing over a dozen seizures a month, despite being on several anti-seizure medications. A 25 mg dose led to a 42.7% placebo-adjusted reduction in seizures, while a 15 mg dose led to a 34.6% reduction. The result was “the highest placebo-adjusted efficacy ever observed in a pivotal epilepsy study,” Xenon CEO Ian Mortimer said in the statement. Xenon’s drug targets specific potassium channels, working as a next-generation version of Potiga, a compound that GSK voluntarily pulled from the market in 2017, citing its limited commercial use. That previous drug was issued a black-box warning by the FDA after reports of drug-induced hyperpigmentation, or turning patients’ skin blue . Xenon’s drug, which it licensed in from a biotech in 2017, was designed to avoid those risks. The most common treatment-emergent side effects in the Phase 3 study were dizziness, headache, somnolence and fatigue, Xenon said. The company is also studying azetukalner in Phase 3 studies for major depressive disorder and bipolar disorder. The company has guided to topline depression data in the first half of 2027. Azetukalner previously fell short in a Phase 2 study in depression. Stifel analyst Paul Matteis called the data a “home run outcome,” highlighting the lower-dose data. Matteis noted discontinuation rates were 14.5% for the high dose and 4.8% for the low dose. He suggested physicians “will have the flexibility to titrate down patients who couldn’t tolerate the highest dose, while still maintaining solid efficacy.” Matteis increased his price target on Xenon’s stock from $66 to $89 on Monday, upping his US peak sales estimate to $2.5 billion. The latest data widen the moat with possible competition like Biohaven’s opakalim and Praxis Precision Medicines’ vormatrigine, Matteis said. Both of those drugs are also in Phase 3 epilepsy studies, with readouts expected this year. Xenon said it will present the Phase 3 results as a late-breaking oral presentation at next month’s American Academy of Neurology annual meeting in Chicago.

Analysts said Biohaven \"will need to be more streamlined in near-term development spend” depending on the readouts from its prioritized assets.\n Biohaven is powering ahead with its bold ambition to sharply reduce R&D spending—even as analysts warn the company will need to be even stricter with its expenditures.Following a regulatory setback in November that left the fate of its spinocerebellar ataxia (SCA) treatment troriluzole tied up in an FDA appeal process, Biohaven decided to prioritize assets stemming from three late-stage platforms: myostatin-activin inhibitors, extracellular protein degraders and Kv7 ion channel activators. The aim at the time was to shrink the company’s annual R&D spend by 60% to focus on the company’s “closest near-term value inflection points,” Biohaven CEO Vlad Coric, M.D., explained to Fierce last month.But such a tight spending restriction was never going to be easy. In Biohaven’s fourth-quarter earnings release, the company reaffirmed its commitment to reducing its spending but warned that this might be impacted by its updated plans for its protein degraders.Specifically, the company announced yesterday that it is accelerating trials of its molecular degrader of extracellular proteins (MoDE) and targeted removal of aberrant protein (TRAP), which are being aimed at Graves’ disease and IgA nephropathy, respectively. The decision follows Biohaven’s announcement last month that a patient with Graves’ disease who received the IgG MoDE degrader, dubbed BHV-1300, had experienced complete suppression of disease-causing TSH receptor-stimulating antibodies.“We continue to expect that the restructuring and optimization efforts that we commenced in the fourth quarter of 2025 will lead to a reduction in annual direct R&D spend, although the acceleration of these trials is expected to reduce the level of that reduction,” Biohaven explained in yesterday’s release. William Blair analysts also homed in on Biohaven’s quest to conserve cash in a note this morning. The company “will need to be more streamlined in near-term development spend” depending on the readouts from its prioritized assets, the analysts suggested in a March 3 note.Those readouts this year include a phase 2/3 study of the Kv7 ion channel activator opakalim in focal epilepsy as well as a phase 2 study of taldefgrobep alfa, a myostatin-activin pathway inhibitor licensed from Bristol Myers Squibb, as a treatment for obesity.Biohaven is also planning to launch pivotal studies of its TRAP degrader, dubbed BHV-1400, in IgA nephropathy this month, followed by the IgG MoDE degrader BHV-1300 in Graves’ disease in the second half of the year.Investors are focused on the degrader programs, according to the William Blair analysts, who described the early biomarker activity in an ongoing BHV-1400 trial as “promising.”“Given that spontaneous improvement in these biomarkers is unlikely (particularly hematuria and proteinuria in IgAN), we view these early signals as encouraging despite lack of placebo comparison and low numbers of patients treated,” the analysts added.Despite these various expensive clinical trial commitments, one area in which Biohaven has identified it can reduce costs is its ongoing phase 2/3 study of its brain-penetrant TYK2/JAK1 inhibitor for the treatment of early Parkinson\'s disease.The company explained that as part of its portfolio prioritization, Biohaven has landed on a “more focused execution plan concentrating on a select number of sites in the U.S.” This should help “optimize efficiency and resource allocation,” the biotech explained.Biohaven ended 2025 with $322 million in the bank and has since raised an additional $178.9 million from selling off shares.