Novartis on Wednesday announced that the U.S. Food and Drug Administration (FDA) granted accelerated approval to Vijoice® (alpelisib) for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy.

Vijoice is the first FDA-approved treatment for PROS, a spectrum of rare conditions characterized by overgrowths and blood vessel anomalies impacting an estimated 14 people per million. In accordance with the Accelerated Approval Program, continued approval may be contingent upon verification and description of clinical benefit from confirmatory evidence.

Kristen Davis, Executive Director of CLOVES Syndrome Community, said:

Today’s approval of the first treatment for PROS offers hope for a better quality of life to patients and families affected by these rare conditions. PROS conditions can be debilitating and disabling and can result in disruptions to everyday activities. Until today, often the only treatment options for patients were surgical or interventional radiology procedures.

PROS conditions can affect quality of life and pose a range of physical, emotional and social challenges for patients and their families, ranging from functional impacts and developmental delays to chronic pain, mobility issues, and feelings of isolation. PROS management can be challenging, requiring collaboration from a multidisciplinary team, and patients and physicians have only had access to interventions focused on symptom management.

Guillaume Canaud, MD, PhD, Necker-Enfants Malades Hospital – AP-HP, the Paris Descartes University, Inserm (INEM Institute Necker Enfants Malades – Centre for Molecular Medicine), said:

I am proud of this outstanding achievement for the PROS community. The EPIK-P1 study results build on our earlier pre-clinical findings and demonstrate the efficacy of Vijoice for select PROS conditions, effectively reducing PROS growths. This is a significant advancement in therapy for PROS with the potential to positively change the treatment trajectory and outcomes for patients.

FDA approval was based on real-world evidence from EPIK-P1, a retrospective chart review study that showed patients treated with Vijoice experienced reduced target lesion volume and improvement in PROS-related symptoms and manifestations. The primary endpoint analysis conducted at week 24 showed 27% of patients (10/37) achieved a confirmed response to treatment, defined as 20% or greater reduction in the sum of PROS target lesion volume. Nearly three in four patients with imaging at baseline and week 24 (74%, 23/31) showed some reduction in target lesion volume, with a mean reduction of 13.7%, and no patients experienced disease progression at time of primary analysis. Additionally, at week 24, investigators observed patient improvements in pain (90%, 20/22), fatigue (76%, 32/42), vascular malformation (79%, 30/38), limb asymmetry (69%, 20/29), and disseminated intravascular coagulation (55%, 16/29). These improvements were observed in subsets of patients across the study population (n=57) who reported symptoms at baseline and at week 24.

Victor Bulto, President, Novartis Innovative Medicines US, said:

The approval of Vijoice marks a turning point for patients who, until now, have not had an approved therapy to specifically address their disease. We are grateful to the physicians, patients and families who participated in the EPIK-P1 trial. We are continuing to invest in studies to advance the scientific understanding of PROS conditions and to understand the full potential of Vijoice.

PIK3CA-related overgrowth spectrum (PROS) is a group of rare disorders that cause overgrowth of parts of the body, due to mutations in the PIK3CA gene. Specific disorders in this spectrum include:

• CLOVES syndrome
• Megalencephaly-capillary malformation syndrome (MCAP syndrome)
• Hemihyperplasia‐multiple lipomatosis syndrome (HHML syndrome)
• Hemimegalencephaly
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
• Fibroadipose hyperplasia (also called fibroadipose overgrowth)

Signs and symptoms of PROS depend on the specific disorder present. Depending on the disorder, they can include having a larger-than-normal brain (megalencephaly), low muscle tone (hypotonia), seizures, intellectual disability, changes in the blood vessels (vascular system), and overgrowth of one area of the body (focal overgrowth) or of multiple areas of the body (segmental overgrowth), with normal growth elsewhere.