(RTTNews) - Novartis has come under increasing pressure after a series of clinical and pipeline setbacks in the second half of 2026, culminating in calls from a major shareholder for changes to the company's board.
The most recent setback came on September 8, when the Phase III HARBOR study of del-desiran in myotonic dystrophy type 1 (DM1) failed to meet its primary endpoint of improving video hand opening time, a measure of hand function. While the study showed signs of activity in secondary and exploratory measures, the trial did not achieve its main goal.
Just days earlier, on September 4, Novartis reported that the Phase III Lp(a)HORIZON study of pelacarsen failed to meet its primary endpoint of reducing major cardiovascular events in patients with elevated lipoprotein (a) and established cardiovascular disease. Although pelacarsen successfully lowered lipoprotein (a) levels, the reduction did not translate into a statistically significant cardiovascular benefit.
Another major blow came on September 1, when multiple studies evaluating rap-cel across autoimmune indications were halted after reports of three deaths linked to a severe immune reaction, according to reports. The suspension affected eight ongoing trials and raised fresh concerns about the program's safety profile.
On August 25, 2026, Novartis revealed the results of the ASTRALS Phase II trial evaluating VHB937 in people with amyotrophic lateral sclerosis (ALS), reporting that the trial did not meet its primary or secondary endpoints and that the company would discontinue the development of VHB937 for ALS. The update was published by EUpALS (European network for Professionals and People with ALS) in its ALS Research News section.
The recent setbacks have reportedly prompted David Samra, managing director at Artisan Partners and a founding partner of International Value Group, one of Novartis' major shareholders, to call for a board reshuffle.
According to Reuters, Samra urged Novartis Chairman Giovanni Caforio to strengthen board oversight of acquisitions and add directors with more dealmaking expertise, arguing that recent pipeline disappointments have raised concerns about the company's acquisition strategy and governance.
However, not everything has been going awry for Novartis this month.
On September 1, the company reported positive Phase III results for remibrutinib in relapsing multiple sclerosis. The REMODEL-1 and REMODEL-2 studies met their primary endpoints, showing significant reductions in annualized relapse rates compared with teriflunomide and favorable safety findings. Novartis plans to pursue regulatory submissions globally.
The company also received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) for Cosentyx in polymyalgia rheumatica. If approved by the European Commission, the therapy could become the first IL-17A inhibitor authorized in Europe for the condition.
According to Novartis' 2026 innovation roadmap, additional late-stage programs remain in development across neuroscience, immunology, cardiovascular disease, kidney disease, and rare disorders, with several regulatory decisions, submissions, and clinical readouts still expected through the remainder of the year.
Among the key upcoming catalysts are a final European Commission decision on Cosentyx in polymyalgia rhematica (PMR), expected by November 2026, following the medicine's positive CHMP opinion. Investors are also awaiting regulatory submissions for remibrutinib after positive Phase III results in relapsing multiple sclerosis, as well as continued development of ianalumab in Sjogren's disease and lupus nephritis.
Another closely watched program is FUB523 (zigakibart), where long-term Phase I/II data presented at the European Renal Association (ERA) Congress showed durable reductions in disease-relevant biomarkers, including Gd-IgA1 and IgA through Week 124, alongside clinically meaningful reductions in proteinuria and stabilization of eGFR, with no new safety signals reported. Zigakibart is currently being evaluated in the Phase III BEYOND study in adults with IgA nephropathy, with readout anticipated in the first half of 2027.
Despite the recent pipeline setbacks, Novartis has reaffirmed its 2026 guidance. Barring unforeseen events, the company expects net sales to grow in the low single-digit range at constant currencies, while core operating income is projected to decline in the low single-digit range. Novartis reported net sales of $54.5 billion and operating income of $17.6 billion in 2025.
Management continues to focus on key growth brands including Kisqali, Kesimpta, Scemblix, Pluvicto, and Leqvio, while advancing a broad late-stage pipeline across oncology, immunology, neuroscience, cardiovascular and renal disease.
While recent trial failures have weighed on sentiment, the company retains one of the industry's largest late-stage pipelines. Investors will now be closely watching upcoming milestones as they could provide further insight into the progress of Novartis' pipeline.
NVS has traded between $121.57 and $170.46 over the past year. The stock closed Friday's trading at $140.37, down 0.39%.