Azetukalner

If approved, RAP-219 could compete with SK Life Science’s Xcopri and Catalyst Pharmaceuticals’ Fycompa.\n A phase 2a trial of Rapport Therapeutics’ focal onset seizure drug candidate has hit its primary endpoint, sending shares in the biotech​​ up more than 157% in premarket trading.The study enrolled 30 people with drug-resistant seizures who were taking a median of three antiseizure medicines such as lamotrigine, levetiracetam and cenobamate. Participants received daily oral doses of RAP-219, Rapport’s TARPγ8-specific AMPA receptor negative allosteric modulator, for eight weeks. The receptor is expressed in parts of the brain associated with seizures but not areas linked to side effects.After eight weeks, 23 of the 27 patients in the primary endpoint analysis had experienced at least a 30% decline in long episodes from baseline. The episodes are an electrographic biomarker for clinical seizure reduction. Rapport reported a 71% median reduction in episode frequency from baseline. Shares in the company jumped 140% to $34.50 at one point in premarket trading.The biotech also reported reductions in clinical seizures, a key secondary endpoint. In an analysis of 25 patients, Rapport found 72% of participants experienced a 50% or greater reduction in clinical seizures from baseline. Almost one-quarter of patients achieved seizure freedom. Rapport tracked a 77.8% median reduction in clinical seizure frequency from baseline. Three patients discontinued treatment because of treatment-emergent adverse events (TEAEs). Almost 80% of TEAEs were grade 1 cases, indicating that they were mild cases. The remaining TEAEs were grade 2. Dizziness, headache and fatigue were the most common TEAEs.Based on the data, Rapport plans to start two phase 3 trials of RAP-219 in the third quarter of 2026. The next steps are to hold an end-of-phase 2 meeting with the FDA, share data from the ongoing eight-week follow-up period and start an open-label long-term safety trial. Those events are all scheduled for this year. Rapport expects to share follow-up data and preliminary long-term results next year.The biotech has predicted that a multibillion-dollar commercial opportunity is open to RAP-219. The forecast reflects an analysis that suggests 30% to 40% of the 3 million epilepsy patients in the U.S. have drug-resistant focal onset seizures.If approved, RAP-219 could compete with SK Life Science’s Xcopri and Catalyst Pharmaceuticals’ Fycompa and potentially against other assets that are currently in development. The pipeline of potential rivals in focal onset seizures includes Biohaven’s BHV-7000, Praxis Precision Medicines’ vormatrigine and Xenon Pharmaceuticals’ azetukalner. 

Jazz Pharmaceuticals will pay milestones as SAN2355 advances, starting with a $7.5 million fee tied to a phase 1 trial.\n Jazz Pharmaceuticals has struck a deal to bolster its epilepsy ambitions, paying Saniona $42.5 million upfront for a preclinical asset designed to address problems faced by GSK’s withdrawn drug Potiga.Dublin-based Jazz is on course to turn its existing epilepsy drug Epidiolex into a blockbuster this year. The Saniona deal gives the company global rights to the next-generation epilepsy drug candidate SAN2355. Saniona began (PDF) GMP manufacturing and toxicology studies for the asset in March, putting it on track to finalize a clinical trial application data package by the end of the year. Jazz will pay milestones as SAN2355 advances, starting with a $7.5 million fee tied to the initiation of the first phase 1 trial. The fee is part of $192.5 million in development and regulatory milestones included in the deal. Jazz is also on the hook for up to $800 million in commercial milestones based on product sales.SAN2355 is a selective small molecule activator of Kv7.2/Kv7.3 potassium channels. GSK’s Potiga showed that potassium channel openers can improve outcomes in patients with partial-onset seizures more than a decade ago, only for regulators to restrict use after reports of discoloration of the skin and retina. The company withdrew the product in 2017, citing (PDF) “very limited uptake” of the drug. Xenon Pharmaceuticals has advanced another potassium channel opener, azetukalner, into phase 3 trials in the belief that the structure of its molecule has fixed the problems that sank Potiga. But Saniona saw a need to go further, specifically by avoiding the Kv7.4/Kv7.5 activation it has identified as the likely driver of urinary retention seen in some recipients of azetukalner and Potiga.SAN2355 selectively activates Kv7.2/Kv7.3 while blocking Kv7.5, a design that Saniona has predicted will reduce urinary retention and adverse effects on the central nervous system. Equally, because SAN2355 is from a different chemical series than Potiga, the biotech sees little risk of skin and retinal discoloration. Convincing Jazz of the merits of SAN2355 gives Saniona its second deal in nine months. The biotech put cash into SAN2355 after licensing essential tremor candidate SAN711 to Acadia Pharmaceuticals for $28 million upfront last year.