Pridopidine

iStock, BeritK The biotech’s Huntingtin-targeting molecule lowered blood levels of the protein and elicited functional improvements in earlier-stage patients, but results were not as robust in other biomarkers or with patients at later stages of the disease. PTC Therapeutics announced new data Monday from a Phase II trial showing that Huntington’s hopeful PTC518 could modify a key disease indicator of the disease. The data received mixed reviews, however, and shares of the biotech nose-dived. In a Monday afternoon note to investors, William Blair analysts said that a “question regarding correlation between [huntingtin] reductions and clinical benefit remains,” but added that the 24-month data should aid FDA dialogue. In the Phase II PIVOT-HD trial , PTC518 lowered blood huntingtin (HTT) protein levels by 23% at the lowest dose (5 mg) for patients with both earlier- and later-stage disease, meeting the trial’s primary endpoint. At a higher 10mg dose, patients at the early stage saw a 39% reduction, with patients at a later stage seeing a 36% drop. Patients with early-stage disease also saw functional improvements and slow-down in disease progression. PTC trumpeted the data as a huge win. “We look forward to discussions on the next development and regulatory steps including the potential for accelerated approval as we work to potentially bring the first disease-modifying therapy to those affected by Huntington’s disease,” CEO Matthew Klein said in a statement . William Blair analysts, citing data presented on the company’s follow-up call Monday, were intrigued but less enthusiastic, noting that patients with later-stage disease did not show any functional benefit on PTC518 and protein reduction in cerebrospinal fluid (CSF) was less robust in these patients. Despite the mixed results, the analysts wrote that they “believe the biomarker and clinical outcomes data at 12 and 24 months in the [earlier stage] patients are likely sufficient for productive conversations with the FDA regarding a registrational path in patients with less advanced disease.” Either way, Wall Street does not seem to be buying PTC’s new data, as the company’s stock slid about 17% by Monday afternoon after the morning announcement. Novartis, for one, appears to believe in PTC518. PTC signed a deal with the Swiss pharma late last year worth up to $2.9 billion. Under the terms of the agreement, PTC would be responsible for development through Phase II, at which point Novartis would take over. If the drug is successfully brought to market, PTC will be entitled to 40% of U.S. profits while Novartis would take 60%. PTC518 is a small molecule that includes a premature stop codon in the Huntingtin mRNA, inducing degradation by cells and lower levels of HTT protein in the cell. Mutations in this protein are thought to be the largest culprit in Huntington’s disease. Regardless of the market reaction, these biomarker data are welcome news for the Huntington’s space, which in the past five years has been beset by disappointments as Roche, Wave Life Sciences and NeuBase Therapeutics have all seen clinical failures or ceased work altogether. There have also been glimmers of light, however, with Prilenia Therapeutics’ pridopidine being accepted in November for European Marketing Authorisation Review. And Wave bounced back last summer with data showing that its next-generation antisense oligonucleotide, WVE-003, lowered HTT levels by 46% in patients’ CSF.