- The Food and Drug Administration has approved the first drug to treat an ultra-rare cluster of conditions caused by mutations in a specific gene, granting an accelerated clearance to a Novartis therapy that's already in use for advanced breast cancer.
- The FDA's clearance of the drug, called alpelisib, is based on real-world evidence from a "chart review" study, which indicated the medicine could help treat the conditions, which are collectively termed PIK3CA-related overgrowth spectrum, or PROS, after the gene that's mutated.
- Prior to this decision, the only treatment options for PROS were surgery or interventional radiology, according to Novartis. Sold as Piqray for breast cancer, alpelisib will be marketed under the brand name Vijoice for severe manifestations of PROS in adults and children two years of age or older.
PROS is a new disease classification, proposed about nine years ago by researchers and patient representatives to describe an array of overgrowth conditions linked to PIK3CA gene mutations. The conditions, which also involve blood vessel anomalies, had been previously considered separate clinical syndromes.
According to Novartis, PROS impacts about 14 people per million, meaning affected individuals in the U.S. likely number only a few thousand.
Several years after the conditions associated with PROS were collectively classified, a French trial of 19 patients given alpelisib, then known as BYL719, suggested blocking PIK3CA could help treat the condition.
The retrospective study sponsored by Novartis reached a similar conclusion, showing treatment could shrink overgrowths in most evaluable individuals, although only in 27% of patients did the reduction reach a prespecified threshold of 20% or more.
Trial investigators also reported improvements in pain, fatigue, blood vessel malformation and limb asymmetry in a majority of patients by week 24 of the study, which involved 57 people who participated in a compassionate use treatment program.
Treatment with Vijoice was associated with side effects also seen in testing of alpelisib for breast cancer, namely diarrhea, stomatitis and hyperglycemia. The most common side effect classified as more severe was cellulitis, which in one adult patient was considered treatment-related.
Novartis priced Vijoice at a wholesale cost of $32,500 per carton, which covers a 28-day prescription. In a statement, the company said it is "continuing to work with payers to maximize patient access to Vijoice."
The wholesale acquisition price for a 28-day supply of Piqray tablets, by comparison, is $18,721, a spokesperson confirmed.
Novartis is studying Vijoice as a PROS treatment in a Phase 2 randomized and placebo-controlled study, as well as a long-term follow-up to its retrospective chart-review study.