Iptacopan Hydrochloride

Roche on Wednesday said its investigational Factor B-directed antisense oligonucleotide (ASO) sefaxersen — which is partnered with Ionis Pharmaceuticals — met the primary endpoint of a Phase III study in patients with primary IgA nephropathy (IgAN) at high risk of progression."Sefaxersen may…offer a new treatment option to help slow disease progression and potentially reduce the long-term need for dialysis or kidney transplantation," said Levi Garraway, Roche's chief medical officer.The IMAgINATION trial randomised 459 participants with IgAN to receive once-monthly subcutaneous sefaxersen or placebo over a 105-week period. The study's main goal was reduction in proteinuria — a key surrogate marker of renal function — measured by change from baseline in 24-hour urine protein-to-creatinine ratio (UPCR) at week 37.Top-line findings from a prespecified interim analysis showed that sefaxersen achieved statistically significant and clinically meaningful proteinuria reductions versus placebo at 37 weeks. The company also noted sefaxersen's safety and tolerability profile aligned with previously reported data, with no new signals identified. Detailed interim data will be presented at an upcoming conference and submitted to regulatory agencies.Meanwhile, IMAgINATION will continue to evaluate the change in kidney function over two years, as measured by estimated glomerular filtration rate (eGFR) at week 105.Earlier this year, Morgan Stanley analysts estimated peak sales of up to CHF 1 billion ($1.2 billion) for sefaxersen — which is intended for self-administration in people with IgAN — despite "several competitors with similar efficacy data." For more, read — Spotlight On: Four things to watch at Roche.The IgAN treatment landscape has strongly flourished in recent times. While Travere Therapeutics' Filspari (sparsentan), Otsuka Pharmaceutical's Voyxact (sibeprenlimab), Novartis' Fabhalta (iptacopan) and Vera Therapeutics' Trutakna (atacicept) have already gained approvals for the indication, Vertex Pharmaceuticals' povetacicept is awaiting an FDA decision in November (for more, see – Spotlight On: Vertex's renal pipeline approaches an inflection point).

Dive Brief:Roche and Ionis Pharmaceuticals said Wednesday their experimental drug for the kidney disorder IgA nephropathy succeeded in a Phase 3 clinical trial, hitting its main goal at an interim data check.Called sefaxersen, the drug led to statistically significant and clinically meaningful improvements in the amount of protein in participants urine, an important marker of kidney health, the companies said. They didnt provide specific details, but said the data will be presented at an upcoming medical meeting and shared with regulators. Theyll also continue monitoring enrollees for two years to monitor changes in kidney function.If approved by regulators, sefaxersen would face competition from multiple drugs launched over the last few years for IgA nephropathy, among them Novartis Fabhalta. Drugmakers have priced those therapies, which could slow disease progression and help patients avert expensive kidney dialysis or transplants, at around $400,000 to $500,000 a year.Dive Insight:IgA nephropathy is an autoimmune disorder that occurs when rogue antibodies enter the kidneys and form clumps that cause inflammation and impede organ function. Its recently become a hotbed for drug research, thanks to a better understanding of the diseases biology and the need for better treatments.Sefaxersen acts on a similar biological pathway as Fabhalta. That target, complement factor B, drives inflammation and kidney tissue damage in IgA nephropathy. Fabhalta directly binds to that protein, whereas sefaxersen, an antisense oligonucleotide, suppresses its production by binding to a messenger molecule in the liver.Roche and Ionis are pitching sefaxersen as a more convenient alternative to Fabhalta. Their drug is self-injected once monthly, while Fabhalta is a twice-daily pill. The shot emerged from one of multiple partnerships between the two companies that has also seen them collaborate on experimental drugs for Huntingtons and Alzheimers disease.But sefaxersen, if approved, would have other competitors to deal with too. Since late last year, the Food and Drug Administration has granted accelerated clearances from Otsuka Pharmaceutical and Vera Therapeutics that act on different protein targets. Another drug from Vertex Pharmaceuticals could soon follow.IgAN remains a large but competitive market, spanning a multitude of targets and dosing regimens, wrote William Blair analyst Myles Minter. Sefaxersens monthly dosing via an autoinjector is relatively competitive, with only Vertexs drug having a similar profile. But the data presentation will be crucial in assessing the drugs comparative benefits and safety, Minter added.Sefaxersen is one of several pipeline assets identified by RBC Capital Markets analyst Trung Huynh as underappreciated by Roche investors. The Swiss pharma giants base business is growing slowly as it absorbs patent expirations for key products. But in a recent research note, Huynh contended that sefaxersen, along with the breast cancer drug giredestrantand the multiple sclerosis treatment fenebrutinib, could boost earnings in the years ahead.An approval would also provide a boost for Ionis, which has seen its share price pressured by multiple setbacks this year. Ionis is due up to $400 million in milestone payments related to sefaxersen and would get sales royalties if the drug is cleared. '