FDA Approves Novartis’ Vijoice as First Approved Treatment for Rare Overgrowth Spectrum Disorder

The U.S. Food and Drug Administration granted accelerated approval to Novartis’ Vijoice for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum who require systemic therapy.

Photo: Victor Bulto, president, Novartis Innovative Medicines US

PIK3CA-Related Overgrowth Spectrum (PROS) is a spectrum of rare conditions and is characterized by atypical overgrowths and anomalies in blood vessels, the lymphatic system, and other tissues. The PROS classification was proposed by researchers and parent representatives of patient-family support and advocacy organizations at a National Institutes of Health workshop in 2013 to unite a group of rare overgrowth conditions caused by PIK3CA mutations. Specific conditions associated with PROS include KTS, CLOVES syndrome, ILM, MCAP/M–CM, HME, HHML, FIL, FAVA, macrodactyly, muscular HH, FAO, CLAPO syndrome and epidermal nevus, benign lichenoid keratosis, or seborrheic keratosis. The estimated prevalence of PROS conditions is approximately 14 people per million.

Vijoice (alpelisib) is a kinase inhibitor that treats rare overgrowth conditions caused by the effects of PIK3CA mutations in adults and children with PROS. It works by inhibiting the PI3K pathway, predominantly the PI3K-alpha isoform. Vijoice is the first FDA-approved treatment for PROS conditions. It is not approved for use outside the United States. In accordance with the Accelerated Approval Program, continued approval may be contingent upon verification and description of clinical benefit from confirmatory evidence.

“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,” said Kristen Davis, executive director of CLOVES Syndrome Community. “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.

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 percent of patients (10/37) achieved a confirmed response to treatment, defined as 20 percent or greater reduction in the sum of PROS target lesion volume. Nearly three in four patients with imaging at baseline and week 24 (74 percent, 23/31) showed some reduction in target lesion volume, with a mean reduction of 13.7 percent, and no patients experienced disease progression at time of primary analysis. Additionally, at week 24, investigators observed patient improvements in pain (90 percent, 20/22), fatigue (76 percent, 32/42), vascular malformation (79 percent, 30/38), limb asymmetry (69 percent, 20/29), and disseminated intravascular coagulation (55 percent, 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.

“The approval of Vijoice marks a turning point for patients who, until now, have not had an approved therapy to specifically address their disease,” said Victor Bulto, president, Novartis Innovative Medicines US. “We are continuing to invest in studies to advance the scientific understanding of PROS conditions and to understand the full potential of Vijoice.”

In EPIK-P1, the most common adverse events (AEs) of any grade were diarrhea (16 percent), stomatitis (16 percent), and hyperglycemia (12 percent). The most common grade 3/4 AE was cellulitis (4 percent); one adult case was considered treatment-related.

Author: Rare Daily Staff