Improving healthcare for all

The FDA approves the world’s first treatment for Cloves syndrome and related syndromes

Thanks to research conducted under the leadership of Pr. Canaud, Vijoice has become the world’s first and only treatment for patients two years of age and over, presenting with the overgrowth spectrum linked to a mutation in the PIK3CA gene.  

29 Apr 2022

This approval is the happy conclusion to a more than six-year journey in two areas: the laboratory and the regulatory arena. It is the culmination of the research conducted by the cross-disciplinary teams led by Professor Guillaume Canaud at Necker-Enfants Malades hospital (AP-HP), the INEM Center for Molecular Medicine, INSERM, the Imagine Institute, and Université Paris Cité. 

Everything began in October 2015 when Pr. Canaud, a nephrologist at AP-HP Paris, was consulted by a young man with kidney disease and a severe form of Cloves syndrome. His condition was life threatening. 

Cloves syndrome, also known as disharmonious hypergrowth syndrome, is caused by a mutation in the PIK3CA gene. The cells multiply in an uncontrolled manner, grow bigger, form benign tumors, and compress all the surrounding organs. Common in oncology patients, it is found in a third of all breast cancer cases. 

So, Novartis developed a molecule to prevent this gene from malfunctioning. The Swiss pharmaceutical firm is currently completing a phase 1 clinical trial. The molecule has since been approved for the treatment of breast cancer in the United States (2019) and Europe (2020), under the name Alpelisib.

“All those involved in the patient care pathway must work very closely together. This includes hospitals, research organizations, pharmaceutical laboratories, and drug regulatory authorities. Together we can move mountains and make sure that patients get quick and early access to innovative treatments,” says Professor Guillaume Canaud. 

In December 2015, the ANSM (French National Agency for the Safety of Medicines and Health Products) issued a special authorization to treat this first patient with the lowest possible dose, administered orally. “His quality of life improved very quickly, his tumors shrank dramatically, and his pain reduced,” explains Pr. Canaud. A mouse model was then developed with the same genetic characteristics. It yielded the same very promising results. 

At the time, only around fifty people worldwide had been officially diagnosed with Cloves syndrome. When he consulted his colleagues at Necker-Enfants Malades hospital, Pr. Canaud realized that this figure was considerably underestimated. This would be confirmed after an article was published in the Nature journal in June 2018. “As a result of the tremendous visibility, we received 4,000 inquiries from doctors and patients all over the world, asking if they could get access to the treatment,… It was crazy!” recalls Pr. Canaud. 

In addition to an INSERM team of 16 researchers, a dedicated department was set up within Necker. Patients from around the world, suffering from deforming diseases, were offered a genetic diagnosis in under three weeks (as opposed to several years in normal times), along with a multidisciplinary program of care (plastic surgery, amputation, medication, etc.). 

Since 2016, 150 patients have been treated, including adults and children over six months, always with special authorization from the regulatory authorities. Pr. Canaud cites, for example, the case of a five-year-old little girl confined to a wheelchair by the tumors compressing her spinal cord. Within just one month, she was walking again. 

A regulatory procedure took place at the same time to get the treatment to market faster. At the beginning of 2020, the FDA authorized a retrospective, real-life study of 57 patients (in France, the United States, Australia, and Ireland) treated with Alpelisib between 2016 and 2019. They all underwent a similar care protocol. The images were analyzed by an external contractor and would inform the FDA’s decision. This had never happened before in the history of the FDA. 

On April 6, 2022, the FDA granted accelerated approval to Vijoice. The dosage is different from Alpelisib, but the chemical structure is exactly the same. 

A conventional clinical trial is currently under way with 150 randomized patients to gather more data and obtain marketing authorization from the European authorities. 

Pr. Canaud is now an expert with the FDA, which plans to use the accelerated approval procedure again in the future, in particular for rare diseases. Vijoice was approved in under four years, when normally it would take 15 to 30.

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