Novartis’ Kinase Inhibitor Gets Rare Tissue Overgrowth Disease Nod From FDA

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Novartis’ targeted cancer drug alpelisib, a kinase inhibitor designed to treat tumors with PIK3CA mutations, has been approved by the U.S. FDA for treatment of the group of rare diseases known as PIK3CA-Related Overgrowth Spectrum (PROS).

This is the first approved treatment for patients with PROS, a condition affecting around 14 people in every million, which causes tissue overgrowths and blood vessel anomalies in those affected. There are several sub-conditions included in this group of disorders including CLOVES syndrome, fibroadipose hyperplasia, and megalencephaly-capillary malformation syndrome.

Alpelisib was first approved by the FDA to treat breast cancers with this kind of mutation in combination with fulvestrant in 2019 (branded as Piqray), and was also approved in Europe by the EMA in 2020.

Instead of going through the normal phase I-III clinical trial program, something that can be a challenge for rare diseases, the accelerated approval of alpelisib (branded as Vijoice), was based on a global, site-based, retrospective, non-interventional review of 57 children (aged two years or older) and adults with PROS treated with alpelisib as part of an expanded access program for compassionate use.

The results of this study, known as the EPIK-P1 trial, show that 27% of the patients included in the study had a reduction in their tissue overgrowth of 20% or more at 24 weeks. In addition, 74% had at least some reduction in volume, with an average reduction of 13.7%. Significant improvements in other symptoms including pain, fatigue, and vascular malformations, were also seen in more than half those treated.

There were treatment related adverse events reported in 39% of cases, 12% considered serious, but none leading to treatment discontinuation. These included diarrhea, stomatitis and hyperglycemia, among others.

“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,” said Guillaume Canaud, a professor at the University of Paris and Necker Hospital for Sick Children, who published findings on the benefits of alpelisib for patients with PROS earlier this year.

“This is a significant advancement in therapy for PROS with the potential to positively change the treatment trajectory and outcomes for patients.”

In a press statement, the company states that continued approval of alpelisib for this indication may be “contingent upon verification and description of clinical benefit from confirmatory evidence,” something that is in accordance with the FDA’s Accelerated Approval Program.

“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 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.”

Novartis is conducting two additional trials to continue evaluation of alpelisib for treatment of PROS, firstly, EPIK-P2 –a prospective phase II multi-center study with a randomized, double-blind, upfront 16-week placebo-controlled period. They will also conduct EPIK-P3 –a Phase II study to assess long-term safety and efficacy of alpelisib in those who participated in EPIK-P1.

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