Abiprubart

Novartis hailed the win as the “first ever global phase 3 trials to demonstrate statistically significant reduction in disease activity for Sjögren\'s disease.”\n Novartis may have abandoned one Sjögren\'s syndrome asset this year, but it looks like the drugmaker has a winner on its hands with another candidate.The Swiss pharma had been evaluating ianalumab, a dual-mechanism, B-cell-depleting antibody that targets the protein BAFF-R, in a pair of phase 3 studies dubbed Neptunus 1 and 2, which in total enrolled 779 patients with the systemic autoimmune disease.Both studies hit their primary endpoint of demonstrating an improvement in disease activity as measured on the EULAR Sjögren\'s syndrome disease activity index at 52 weeks compared to placebo, Novartis announced in an Aug. 11 release. The drug was also well tolerated and demonstrated a favorable safety profile, according to the pharma.The company hailed the win as the “first ever global phase 3 trials to demonstrate statistically significant reduction in disease activity for Sjögren\'s disease.” For now, Novartis is holding back the data for a future medical conference, while referencing plans to take the results to global regulators with the aim of bringing the first targeted treatment for the autoimmune disease to market.“Sjögren\'s disease is a serious, progressive, systemic autoimmune disease, often unrecognized or misdiagnosed with a significant detrimental impact to quality of life, with very limited treatment options and an established unmet need,” Novartis Chief Medical Officer Shreeram Aradhye, M.D., said in the release.“Both phase 3 trials demonstrate that ianalumab improves disease activity in patients with Sjögren\'s disease,” Aradhye added. “These phase 3 studies mark a significant milestone. We look forward to engaging with health authorities to discuss these findings in the near future.”It’s a big win for Novartis, which started the year dropping its anti-CD40 antibody iscalimab after becoming doubtful of its competitive profile. That left ianalumab as Novartis’ last and best hope for the disease.Ianalumab had already shown \"meaningful differences in patients with this very difficult-to-treat disease” in phase 2, Novartis executives pointed out at the time.Iscalimab was only the latest Big Pharma prospect to fail to make the grade in Sjögren\'s. Last year, Sanofi crossed off Sjögren’s from the list of targeted indications for its CD40L monoclonal antibody frexalimab after seeing phase 2 efficacy data, while, more recently, Kiniksa Pharmaceuticals ended work on its own Sjögren\'s prospect abiprubart. While Novartis had always sounded positive about the potential of ianalumab in the automimmune disease, the therapy has faced its own clinical setbacks. Only last month, the company reported that the B-cell-depleting antibody had failed to hit the efficacy threshold in a phase 2 study for a painful skin condition called hidradenitis suppurativa.Ianalumab\'s story begins with Novartis’ collaboration with MorphoSys, before the Big Pharma went on to buy the biotech last year. The therapy is also being investigated for other B cell-driven autoimmune diseases like immune thrombocytopenia, systemic lupus erythematosus, lupus nephritis, warm autoimmune hemolytic anemia and diffuse cutaneous systemic sclerosis.

iStock, cagkansayin Kiniksa will now focus its development efforts on the IL-1 blocker KPL-387, which it is testing for recurrent pericarditis with Phase II/III trials planned for mid-2025. Kiniksa Pharmaceuticals will no longer move forward with its Sjögren’s syndrome drug development program and will walk away from an investigational antibody licensed from AstraZeneca, the London-based biotech announced on Tuesday. In Sjögren’s, Kiniksa was testing abiprubart, a monoclonal antibody that targets the CD40 protein, which is highly expressed in specific types of immune cells. In autoimmune diseases such as Sjögren’s, this mode of action could potentially disrupt pathological pathways that would otherwise culminate in a defective immune response that attacks healthy cells. Before being shelved, abiprubart was one of Kiniksa’s most mature assets. In July 2024, the biotech kicked off its Phase IIb study for the asset, testing biweekly and monthly dosing schedules in approximately 200 patients. The decision to discontinue abiprubart is in line with Kiniksa’s “strategic reprioritization of its portfolio and certain capital allocation considerations,” the biotech wrote in an SEC filing dated Feb. 21. The company will “immediately” stop enrollment into abiprubart’s mid-stage study and start winding down activities linked to the asset, while looking for strategic alternatives. Abiprubart’s termination has already cost Kiniksa $19 million, and the biotech expects to incur around $14 million to $17 million more in discontinuation expenses, mostly attributed to “contract termination costs” for existing supply agreements. Kiniksa expects to wrap up wind-down activities for abiprubart by the end of the year. Other players in the Sjögren’s syndrome space include J&J and Horizon Therapeutics , which reported respective mid-stage wins in June 2024 and January 2023. Also on Tuesday, Kiniksa announced it is terminating its licensing deal with AstraZeneca’s MedImmune for the GM-CSF blocker mavrilimumab. The asset, also a monoclonal antibody, was being tested for the chronic autoimmune disease giant cell arteritis and COVID-19-related acute respiratory distress syndrome. Kiniksa entered its licensing deal with MedImmune in December 2017, paying $23 million in upfront, pass-through and certain clinical milestone payments. At the time, the London biotech also promised up to $57.5 million in future milestones for the first two programs covered by the contract, plus up to $15 million for additional indications. In January 2024, however, Kiniksa announced it had slowed down investment into mavrilimumab and was in the process of looking for potential development partners for the asset. With abiprubart and mavrilimumab discontinued, Kiniksa is down to a completely cardiovascular pipeline —though the indication for its most immature candidate, the IL-1 antagonist KPL-1161, has yet to be disclosed. As per its Tuesday press release, Kiniksa will now focus its development efforts on KPL-387, also an IL-1 blocker, for recurrent pericarditis. The biotech is gearing up for a Phase II/III trial of the asset in mid-2025.