Novartis Cosentyx® PMR data in New England Journal of Medicine showed sustained remission vs placebo in twice as many patients

Novartis Cosentyx Phase III REPLENISH Data Shows Sustained Remission in PMR

Novartis announced positive Phase III REPLENISH trial results for Cosentyx (secukinumab) in polymyalgia rheumatica (PMR), demonstrating statistically significant and clinically meaningful efficacy. The data, published in the New England Journal of Medicine and presented at EULAR 2026, showed that Cosentyx treatment led to sustained remission rates approximately twice as high as placebo at week 52. Furthermore, patients receiving Cosentyx achieved significant reductions in steroid use, addressing a critical unmet need in PMR management. The trial met all primary and secondary endpoints, and the safety profile was consistent with previous observations for Cosentyx. These findings support regulatory submissions in the US, EU, and Japan.

• The Phase III REPLENISH trial demonstrated superior efficacy for Cosentyx in polymyalgia rheumatica, with 41.2% of patients on 300mg and 40.6% on 150mg achieving sustained remission at week 52, significantly higher than 20.4% for placebo (p-value < 0.001). Additionally, Cosentyx significantly reduced the mean adjusted annual cumulative glucocorticoid dose to 1604mg (300mg) and 1683mg (150mg) compared to 2093mg for placebo, addressing a critical need to reduce steroid reliance.
• Following these robust results, Novartis has submitted Cosentyx for health authority review for PMR in the US, EU, and Japan, with additional country filings planned throughout 2026. This addresses a significant unmet need for advanced treatments in PMR, a chronic inflammatory disease where current standard of care involves long-term steroid use with associated risks and frequent relapses, impacting patients over 50.
• The REPLENISH trial, a global Phase III, multicenter, randomized, double-blind, placebo-controlled study across 27 countries, evaluated Cosentyx 300mg and 150mg in combination with a 24-week steroid taper regimen. The study confirmed that Cosentyx's known safety profile remained consistent in PMR patients, with no new safety signals identified, reinforcing its potential as a long-term treatment option.

Addressing Unmet Needs in Polymyalgia Rheumatica Treatment

Current treatment approaches for polymyalgia rheumatica face significant challenges that impact both efficacy and patient safety. While glucocorticoids remain the mainstay therapy, substantial limitations exist in optimizing their use and managing their associated risks. The need for evidence-based treatment protocols and effective steroid-sparing alternatives continues to drive clinical research efforts.

• Prolonged glucocorticoid dependency and high relapse rates — Treatment typically requires 1-2 years of glucocorticoid therapy, with relapses occurring in 40-60% of patients during tapering, and one-third experiencing disease recurrence even after achieving remission

• Significant glucocorticoid-related adverse events — Side effects occur in 22.7% of patients and are particularly problematic in elderly populations, with vertebral fractures and infections among the most serious complications of long-term corticosteroid therapy

• Lack of evidence-based tapering protocols — Guideline recommendations for steroid tapering regimens are largely based on expert consensus rather than controlled studies, with no robust evidence to guide optimal initial dosing or tapering strategies

• Individual variability in treatment response — Prednisone pharmacokinetics vary significantly between patients, with weight-based dosing being a critical factor, making steroid tapering more of an art requiring individualized approaches

• Complex disease monitoring challenges — Assessment of disease activity is complicated by comorbidities such as osteoarthritis, and acute phase reactants may not reliably indicate flares during treatment, while the role of imaging in disease activity assessment remains incompletely defined

• Variable disease course requiring long-term management — The disease course is not uniformly monophasic, with some patients requiring therapy longer than four years and others experiencing recurrence after prolonged disease-free intervals

• Limited availability of proven steroid-sparing agents — While IL-6 inhibitors like tocilizumab and sarilumab show promise, and methotrexate may be useful in refractory cases, randomized controlled trials with new immunosuppressive agents are still needed to establish optimal glucocorticoid-sparing strategies

REPLENISH Trial Design and Positive Cosentyx Results

Recent clinical trials in polymyalgia rheumatica have primarily focused on tocilizumab as a steroid-sparing therapy, with several key studies demonstrating significant efficacy in achieving glucocorticoid-free remission. The most robust evidence comes from randomized controlled trials and meta-analyses examining tocilizumab's role in PMR treatment, along with established core domain sets for standardizing trial endpoints.

Cosentyx's Potential to Reshape PMR Treatment

Recent clinical trials have demonstrated that investigational IL-6 receptor blocking agents, particularly tocilizumab and JAK inhibitors like baricitinib, show superior efficacy compared to standard glucocorticoid monotherapy in polymyalgia rheumatica. In a 2022 randomized controlled trial, tocilizumab achieved glucocorticoid-free remission in 63.2% of patients versus 11.8% receiving placebo (OR 12.9, 95% CI: 2.2-73.6), while also extending time to first relapse (130±13 days versus 82±11 days) and reducing cumulative glucocorticoid exposure. Similarly, baricitinib demonstrated remarkable efficacy in a 2025 trial, with 78% of participants achieving the primary endpoint compared to 13% in the placebo group (relative risk 5.8, 95% CI 3.2-10.6).

Methotrexate has emerged as the most established steroid-sparing agent, with moderate to high-quality evidence supporting its use in early PMR. A landmark 2004 multicenter trial showed that 87.5% of patients receiving methotrexate plus prednisone were able to discontinue prednisone at 76 weeks compared to 53.3% receiving placebo (P=0.003), with a 34 percentage point risk difference and significant reduction in cumulative prednisone dose (2.1g versus 2.97g). These findings contrast sharply with standard glucocorticoid therapy, where prolonged treatment remains common, with median continuous treatment duration of 15.8 months and approximately 25% of patients requiring more than 4 years of therapy.

The safety profiles of investigational therapies appear favorable compared to the well-documented risks of prolonged glucocorticoid use, which causes serious adverse effects in 48-65% of patients, including vertebral fractures and infections. Current 2025 guidelines now recommend IL-6 receptor blocking agents for relapsing disease and consideration in new-onset PMR patients at high risk for glucocorticoid-related adverse events, representing a significant shift from traditional glucocorticoid monotherapy. Anti-TNF agents have proven ineffective, while the role of rituximab as an alternative steroid-sparing option continues to be evaluated.