The U.S. FDA’s release this morning of its briefing documents for Friday’s advisory committee meeting on obeticholic acid (OCA) 25 mg as a treatment of pre-cirrhotic liver fibrosis due to nonalcoholic steatohepatitis (NASH) sent Intercept Pharmaceuticals Inc. on a downwards spiral. Intercept stock (NASDAQ:ICPT) dropped as low as $11.41 this morning – down nearly 30% from yesterday’s close of $16.21 – before recovering a bit in heated trading. The Street reaction reflected the FDA’s efficacy and safety concerns. Noting that NASH requires life-long drug therapy, the agency said trial results indicated OCA 25 mg “causes multiple off-target effects, making it challenging to develop and implement effective risk mitigation.”

Aphenity phase III study with PTC’s sepiapterin positive in phenylketonuria 

PTC Therapeutics Inc. rolled out favorable results from Aphenity, the phase III study with sepiapterin in adult and pediatric patients with phenylketonuria (PKU). The placebo-controlled portion of the study included 98 patients in the primary analysis population. The mean percentage of phenylalanine (Phe) reduction in sepiapterin treated patients was 63%. In the subset of classical PKU patients, the number was 69%. Minimal reductions in Phe levels turned up in placebo-treated patients, resulting in a highly statistically significant sepiapterin treatment benefit. Sepiapterin is a precursor to intracellular tetrahydrobiopterin, which is a critical enzymatic cofactor in the metabolism and synthesis of many metabolic products. Shares of South Plainfield, N.J.-based PTC (NASDAQ:PTCT) were trading midday at 57.14, up $2.94, or 5%.

Infection gains build on X4’s WHIM drug promise

Heightening prospects for an oral neutropenia therapy, X4 Pharmaceuticals Inc.’s lead CXCR4 antagonist mavorixafor slashed yearly infection rates in patients with WHIM syndrome by 58% in a pivotal phase III trial, an effect that was statistically significant. Amongst 31 patients aged 12 and older who were randomized to receive either a single, daily oral 400-mg dose of the small-molecule drug or placebo, mavorixafor reduced the numbers of infections per year to fewer than 1 vs. 4.5 for those on placebo, with the difference achieving statistical significance during the second six months of the trial. Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare, congenital, combined immunodeficiency disease caused by over-signalling of the CXCR4/CXCL12 pathway. 

Newco news: Sania targets neural circuit dysfunction with R-scan, Neu-scan

Sania Therapeutics Inc. is setting out its stall at the American Society of Cell and Gene Therapy conference in Los Angeles this week, after generating proof of concept for its chemogenetics approach to treating motor disorders. The company has engineered adeno-associated viral (AAV) vectors that can be targeted to specific cell types. It will use these to deliver well-characterized ion channels to dysfunctional motor neurons. The ion channels will then be selectively controlled by an activating drug, which is taken orally. Titrating the dose will enable control of excitability of neurons. “The precision that you can get from matching up [the ion channel] that you’re expressing [with] the exogenous drug, really gives you a great therapeutic index, because you can specifically target those cells and titrate activity,” said Andy Murray, Sania CEO.

Pfizer, Sanofi, and others prep for vast RSV market, behind GSK’s Arexvy

With GSK plc’s Arexvy approved in the U.S. as the first respiratory syncytial virus (RSV) vaccine, several other developers are lining up for what in five years could be a $10 billion market. Their aim is to provide lasting protection for those most susceptible to the endemic virus, particularly young children and those older than 60. Behind GSK is Pfizer Inc. with PF-06928316, which has a U.S. FDA PDUFA date set for this month, and Sanofi SA’s nirsevimab, for which FDA action is expected in the third quarter. Other players in the space are Moderna Inc., Bavarian Nordic A/S, Novavax Inc. and Icosavax Inc.

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