Novartis Q3 Growth Masks Thin Pivotal Detail on Three Pipeline Wins

Novartis Reports Strong Q3 2026 Financials and Key Pipeline Progress

Novartis reported solid Q3 2026 financial results, with net sales growing 4% (cc) to USD 14.5 billion and core operating income increasing 10% (cc) to USD 6.0 billion. This strong performance, driven by priority brands like Kisqali, Kesimpta, and Scemblix, led the company to raise its full-year 2026 core operating income guidance. The quarter also saw significant pipeline advancements, including positive Phase III results for remibrutinib in relapsing multiple sclerosis, new FDA and China approvals for Pluvicto in prostate cancer, and FDA and Japan approvals for Fabhalta in IgA nephropathy.

• Novartis delivered robust Q3 2026 financial results, with net sales reaching USD 14.5 billion (+4% cc) and core operating income growing 10% (cc) to USD 6.0 billion. This strong performance, coupled with productivity efforts, enabled the company to upgrade its full-year 2026 core operating income guidance from a low single-digit decline to being in line or growing low single-digit.
• Sales growth was primarily driven by the continued strong performance of key priority brands. Kisqali saw a 37% (cc) increase, Kesimpta 22% (cc), Scemblix 67% (cc), Leqvio 63% (cc), and Cosentyx 9% (cc). These brands demonstrated significant market share growth and strong demand across various regions and indications, effectively offsetting generic erosion.
• The company achieved several significant R&D milestones, including positive Phase III results for oral remibrutinib in the REMODEL-1 and -2 trials for relapsing multiple sclerosis, meeting primary and key secondary endpoints. Additionally, Pluvicto received FDA and China NMPA approvals for PSMA+ metastatic androgen pathway modulation-naive/sensitive prostate cancer, and Fabhalta gained FDA and Japan MHLW approvals for IgA nephropathy.
• Novartis further advanced its pipeline with regulatory submissions for pelabresib in myelofibrosis in the EU and for Vanrafia in IgAN in Japan and China. Del-zota was granted FDA Priority Review for Duchenne muscular dystrophy (DMD44). Strategic transactions included the acquisition of Myricx Bio to strengthen the oncology pipeline and a licensing agreement with Abogen Biosciences for RNA-encoded therapeutics.

Addressing the Unmet Needs in Relapsing Multiple Sclerosis Treatment

Current approaches for relapsing multiple sclerosis primarily manage symptoms and slow disease progression but do not achieve remyelination or address the root causes of disease, with patient responses varying significantly. Their limited clinical efficacy reflects a focus on blocking the proinflammatory response, while progression independent of relapse activity and long-term disability remain insufficiently controlled.

• Absence of remyelination and neuroprotection: Current therapies primarily manage symptoms and slow disease progression but do not achieve remyelination, and convincing evidence of true remyelination is limited to a subset of disease-modifying treatments. There is insufficient proof to claim that changes in surrogate markers such as advanced imaging and electrophysiological techniques can be explained by remyelination alone.

• Persistent progression despite inflammatory control: Treatment of progression independent of relapse activity (PIRA) is a relevant unmet need, being only modestly affected by disease-modifying treatments which target predominantly adaptive immunity in the periphery. No evidence of disease activity-3, defined as absence of clinical relapse, disability progression, and brain magnetic resonance imaging activity, might not be sufficient to prevent cognitive deterioration and predict long-term disability, with significant brain volume loss observed even in patients achieving NEDA-3.

• Safety, tolerability and adherence burden: Efficacy is often hindered by poor persistence and adherence, impacted by patient-perceived efficacy concerns, adverse effects, inconvenience, and forgetfulness. Risks include severe side effects, serious lymphopenia, reactivation of latent or opportunistic infections, drug-induced liver injury, malignancy imbalance in short-term data, hypogammaglobulinemia and infections with sustained immunosuppression, and natalizumab-associated progressive multifocal leukoencephalopathy.

• Rebound risk and sequencing complexity: Discontinuation or de-escalation of therapy is associated with a significant risk of disease reactivation, particularly after lymphocyte-trafficking inhibitors, with probability of having a relapse within the year following discontinuation of 6% for first-line DMT, 9% for fingolimod and 43% for natalizumab. Treatment-specific immunologic effects strongly influence optimal sequencing, including increased risk of relapse and worsening disability when switching from fingolimod to immune cell depletion, and need for short transition intervals and proactive transition planning to maintain disease control.

• Evidence and measurement limitations: Trials are limited by small sample sizes, short follow-up periods, and lack of standardized clinical endpoints validating remyelination's functional impact. Evidence for disease-modifying therapies in patients aged over 50 years is limited because this population is often excluded from randomized trials, and research efforts should be dedicated to novel biomarkers to assess repair mechanisms.

Remibrutinib's Promising Phase III Efficacy and Safety in RMS

Recent studies in relapsing multiple sclerosis have evaluated monoclonal antibodies and sphingosine 1-phosphate receptor modulators in randomized trials and real-world cohorts. Efficacy assessments centered on annualized relapse rate, confirmed disability progression, no evidence of disease activity, and magnetic resonance imaging measures alongside safety monitoring.

• ENSEMBLE, a 4-year, international, multicenter, single-arm, open-label, phase IIIb study, evaluated IV ocrelizumab 600 mg every 24 weeks as first-line therapy in treatment-naive patients with early-stage relapsing-remitting multiple sclerosis. At week 192, 66.4% had NEDA-3 (n = 394/593), 85.0% had no MRI activity, 90.9% had no relapses, and 81.8% had no 24-week CDP, with adjusted ARR of 0.020 (95% CI 0.015-0.027) and NfL levels reduced to and remained within the healthy donor range by week 48 and week 192, respectively. No new or unexpected safety signals were observed.

• SUNBEAM and RADIANCE, randomized, double-blind trials, evaluated ozanimod 0.46 mg or 0.92 mg daily or interferon β-1a 30 µg weekly in relapsing multiple sclerosis. Median percentage reduction in plasma neurofilament light chain concentration at 12 months in SUNBEAM and 24 months in RADIANCE was greater for ozanimod (20%-27%) than interferon β-1a (13%-16%; p < 0.01), with greater reduction associated with fewer GdE lesions, fewer new/enlarging T2 lesions per scan, less loss of brain volume, lower ARR, and no evidence of disease activity.

• Simulated treatment comparison of ofatumumab in ASCLEPIOS I/II versus ocrelizumab in OPERA I/II compared anti-CD20 monoclonal antibody therapies in relapsing multiple sclerosis. Ofatumumab showed significant improvement in ARR versus ocrelizumab (rate ratio: 0.60 [95% CI: 0.43-0.84]), with comparative results not significant for 3-month CDP (hazard ratio [HR]: 0.90 [95% CI: 0.57-1.42]) or 6-month CDP (HR: 0.84 [95% CI: 0.47-1.49]), and significantly favorable results for NEDA-3 and MRI outcomes.

• A retrospective, multicenter study of ofatumumab in 424 adults with relapsing multiple sclerosis with mean follow-up of 1.32 (± 0.61) years evaluated treatment-naive patients and switchers. During treatment, ARR decreased significantly from 0.486 to 0.027 (94.5% reduction; p < 0.001), MRI activity was significantly diminished, and at 12 months, 79.3% of evaluable patients achieved NEDA-3. Ofatumumab was well tolerated with predominantly mild injection-related reactions and low discontinuation rates, while infections occurred in 0.9% of naïve patients, 1.7% of MET switchers, and 9.5% of HET switchers (p = 0.001).

Remibrutinib's Position in the Emerging BTK Inhibitor Landscape for RMS

Remibrutinib (LOU064) is a potent, highly selective covalent BTKi with a promising preclinical and clinical profile for MS. Second-generation BTK inhibitors, including evobrutinib, tolebrutinib, fenebrutinib, and orelabrutinib, have advanced through Phase II-III development in MS.