EMA Grants Conditional Approval for Vijoice, First Treatment for Rare PIK3CA-Related Overgrowth Disorders
Key Insights
The European Medicines Agency (search) has recommended conditional marketing authorization for Vijoice (alpelisib) to treat severe PIK3CA-related overgrowth spectrum disorders (search) in adults and children aged 2 years and older.
The PI3 kinase (search) inhibitor demonstrated a 37.5% response rate in a compassionate use study, with 12 of 32 patients showing at least 20% reduction in lesion size after 24 weeks.
This represents the first authorized medicine for PROS (search) disorders, which currently have no approved treatments and rely solely on supportive care including surgery.
The European Medicines Agency (search) (EMA) has recommended granting conditional marketing authorization for Vijoice (alpelisib) to treat adults and children aged 2 years and older with severe or life-threatening PIK3CA-related overgrowth spectrum (PROS (search)) disorders. This marks the first authorized medicine for these rare genetic conditions, which currently have no approved treatments.
Addressing Critical Unmet Medical Need
PROS (search) represents a diverse group of rare genetic conditions characterized by uncontrolled growth of body tissues, causing malformations and lesions affecting the skin, bones, blood vessels, and brain. The severity ranges from localized overgrowth to severe, extensive, and life-threatening overgrowth affecting important organs or blood vessels.
Currently, treatment consists solely of supportive care, including surgery and procedures to block overgrown blood vessels. The disorders are caused by mutations in the PIK3CA gene, which lead to production of an abnormal form of PI3 kinase (search) enzyme involved in cell growth, resulting in tissue overgrowth and malformations.
Mechanism and Clinical Evidence
Vijoice contains alpelisib, a PI3 kinase (search) inhibitor that works by blocking the abnormal enzyme activity, thereby reducing abnormal tissue growth. The drug is available as tablets and granules for patients with severe or life-threatening PROS (search) manifestations requiring systemic therapy.
EMA's recommendation is based on a retrospective review of medical records from 57 patients aged 2 years and older who received alpelisib through a compassionate use program. All patients had severe or life-threatening PROS (search) symptoms requiring systemic treatment.
The primary efficacy measure was the proportion of patients achieving at least 20% reduction in the size of 1 to 3 abnormal growths or lesions after 24 weeks of treatment, assessed primarily through imaging scans. Of the 32 patients evaluated at 24 weeks, 37.5% (12 patients) responded to Vijoice treatment.
Safety Profile and Regulatory Pathway
The most common side effects reported with Vijoice included hyperglycemia, diarrhea, headache, stomatitis, alopecia, dermatitis, dry skin, and nausea. A follow-up study involving patients from the compassionate use program provided additional supportive evidence regarding the medicine's safety and efficacy.
EMA consulted clinical experts with PROS (search) treatment experience in reaching its decision. The conditional marketing authorization represents one of the EU's regulatory mechanisms to facilitate early access to medicines addressing unmet medical needs, allowing approval with less complete data when immediate patient benefit outweighs inherent risks.
Next Steps and Market Access
Novartis Europharm Limited will conduct additional studies to further confirm Vijoice's efficacy and safety in treating adult and pediatric PROS (search) patients. The CHMP opinion will now proceed to the European Commission for EU-wide marketing authorization decision.
Following marketing authorization, individual Member States will make price and reimbursement decisions based on the medicine's potential role within their national health systems. Vijoice received orphan medicinal product designation for PROS (search) on March 26, 2021, and the Committee for Orphan Medicinal Products will assess whether this designation should be maintained.
Notably, alpelisib is already authorized in the EU as Piqray for treating certain PIK3CA-mutated breast cancers in combination with fulvestrant, demonstrating the drug's broader therapeutic potential across PIK3CA-driven conditions.