Novartis Vijoice receives conditional approval in EU as first systemic PROS-targeted therapy
First systemic therapy for PROS in the EU
The European Union Executive Committee conditionally approved Novartis (NVS)'s Vijoice (alpelisib) on July 15, 2026. The indication is for patients aged two years and older with severe or life-threatening PIK3CA-related overgrowth syndrome (PROS) who require systemic therapy, with the therapy stage being approved and marketed. Alpelisib inhibits phosphatidylinositol 3-kinase alpha (PI3Kα) produced by mutated PIK3CA, reducing abnormal tissue growth and shifting the treatment paradigm from reliance on repeated surgeries and symptom control to disease-targeted therapy.
Conditional approval to supplement limited evidence
The approval is based on EPIK-P1, a retrospective study analyzing medical records of 57 patients from an expanded access program. Among 32 patients who could undergo 24-week imaging assessments, 12 (37.5%) achieved a reduction of 20% or more in target lesion volume. Due to the limitations of real-world evidence without a randomized control group, the EMA determined that the immediate benefit outweighs the data uncertainty and opted for conditional approval. Diarrhea, stomatitis, and hyperglycemia are major adverse reactions reported at a frequency of 10% or more in U.S. approval data, and long-term safety monitoring of growth and metabolism in pediatric patients is critical for commercial expansion.
Regulatory strategy after withdrawal and re-entry
Novartis withdrew its first EU application on October 30, 2023, as it failed to address data requested by the CHMP within the review timeline. However, after resubmission, it secured a positive CHMP opinion on May 21, 2026, followed by approval from the Executive Committee on July 15, 2026. The U.S. FDA had previously granted accelerated approval to Vijoice on April 5, 2022, without a separate AdComm vote. In the EU, orphan drug designation and a 10-year market exclusivity incentive apply. EPIK-P4, an ongoing single-arm Phase 2 trial with a 48-week core period and a potential 2-year extension, is the key source of confirmatory evidence that will determine the continuation or conversion of the conditional approval.
Orphan market exclusivity and next-generation competition
The prevalence of PROS is approximately 14 cases per million people, making the patient population small. However, the status as the first approved systemic therapy and the high medical need support a focused orphan disease business model. Novartis reported combined peak sales of Piqray and Vijoice at USD 382 million in 2025, a 15% decline from the previous year, primarily due to intensified competition for Piqray in breast cancer. Vijoice's EU entry serves as a defensive strategy for the same molecule portfolio. Current management relies on surgery, sclerotherapy, and off-label sirolimus (an mTOR inhibitor), while Relay Therapeutics (RLAY)'s variant-selective PI3Kα inhibitor zovegalisib (RLY-2608) is pursuing the 277-patient ReInspire Phase 2 trial to catch up.
In the short term, the July 15, 2026 EU conditional approval of Vijoice marks Novartis' capture of the severe PROS market for patients aged two years and older in Europe, following the U.S., and securing a 10-year orphan drug exclusivity foundation. From an investment perspective, although the prevalence of PROS is limited at approximately 14 cases per million people, the combined 2025 sales of Piqray and Vijoice reached USD 382 million, with potential for growth from new EU patients and shared alpelisib manufacturing infrastructure. For researchers and clinicians, the efficacy, growth, and metabolic safety data from the Phase 2 EPIK-P4 trial will be critical in determining the continuation of the conditional approval. The mid-to-long-term competitive landscape is shifting from surgery, sclerotherapy, and off-label sirolimus to the Phase 2 zovegalisib, with variant selectivity and tolerability determining Novartis' market defense.
Source: EMA (ema)