Genetic mutations are at the root of “PROS,” a group of rare and debilitating diseases characterized by tissue overgrowth, reduced mobility, and chronic pain. A Novartis drug that interferes with these disease progression pathways is now FDA-approved, making it the first therapy the agency has authorized to treat patients with PROS.
This Regulatory decisions Announced Wednesday, it is for patients 2 years of age and older with severe cases of PROS requiring systemic treatment. The drug alpelisib will be marketed under the name “Vijoice” for PROS.
The acronym PROS stands for PIK3CA-Related Overgrowth Spectrum. PIK3CA is a gene that provides instructions for making phosphoinositide 3-kinase, an enzyme that plays a key role in cell growth. Mutated versions of the protein cause cells to grow and divide abnormally. Alpelisib is a kinase inhibitor designed to block mutant enzymes.
Basel, Switzerland-based Novartis first tested alpelisib as a treatment for cancer. In 2019, the FDA Approved A drug used to treat cases of advanced breast cancer characterized by PIK3CA mutations. The drug’s efficacy was evaluated in a pivotal study of 572 patients. The approval of alpelisib in breast cancer, including in combination with the approved endocrine therapy fulvestrant, makes the Novartis drug the first approved PI3K inhibitor. For cancer indications, the pharmaceutical giant markets alpelisib under the name “Piqray.” The drug had sales of $329 million last year, according to Novartis’ financial statements.
The way alpelisib intervenes in the abnormal cell growth characteristic of breast cancer is also applicable to abnormal cell growth in other tissues in other parts of the body. Mutations in PIK3CA can lead to overgrowth of fat, muscle, nerve, and bone tissue. PROS disease can also manifest as vascular malformations and skin lesions. Treatment for PROS includes surgery or interventional radiology.
According to Novartis, the prevalence of PROS is approximately 14 cases per million people. The PROS classification stems from a 2013 NIH workshop where PROS researchers, support groups, and advocacy groups proposed grouping overgrowth conditions caused by mutations in PIK3CA. Diseases that fall under the PROS umbrella include KTS, CLOVES syndrome, FAVA, and CLAPO syndrome.
For PROS, Novartis tested alpelisib in a single-arm study using real data. The FDA said PROS patients 2 years and older were given the once-daily drug for compassionate use under the expanded access program. The efficacy of alpelisib in PROS was evaluated in 37 patients with at least one lesion identified by medical imaging within 24 weeks prior to receiving the first dose of the drug. The primary objective was to measure at week 24 the proportion of patients with a radiographic response, defined as a 20% or more reduction in lesion volume. The study also assessed the duration of response to treatment. Of the 37 patients, 27% had a radiographic response at week 24; of these responders, 60% had a response lasting 12 months or longer. The most common adverse reactions reported in the study were diarrhea, oral inflammation and pain, and hyperglycemia.
Vijoice’s regulatory decision was based on accelerated approval with less evidence than would normally be required. Remaining approved may require Novartis to provide additional clinical data to confirm the drug’s benefit.
Kristin Davis, executive director of the CLOVES Syndrome Community, said in a prepared statement: “Today’s approval of the first PRS treatment offers hope for a better quality of life for patients and families affected by these rare diseases. “PROS conditions can be debilitating and disabling, and can lead to disruptions in daily activities.”
Photo by Novartis
