Published on 21.04.2022
Research Acceleration
The Food and Drug Administration (FDA) has just approved alpelisib (Novartis) for the treatment of PIK3CA-related dysharmonic hypergrowth syndromes. Patients suffering from this syndrome of overgrowth and vascular anomalies present pain, inflammatory outbreaks, infections, but especially all malformations of certain parts of the body.
In the most severe forms, the prognosis is life-threatening. Alpelisib - already used in breast cancer - thus becomes the first and only drug approved by the US Food and Drug Administration for the treatment of PIK3CA mutation-related dysharmonic hypergrowth syndrome in children aged 2 years or older and adults.
A therapeutic success ...
This therapeutic success is based on the tenacity of Professor Guillaume Canaud's team (Necker Hospital - Sick Children AP-HP/INEM - Centre for Molecular Medicine - Inserm / Institut Imagine / Université Paris Cité), whose pioneering work has led to a better understanding of the disease, its mechanisms of action and its progression thanks to the development of the first mouse model of the disease. This preclinical work enabled him to identify a molecule - BYL719 or alpelisib - that is highly effective in inhibiting the abnormal PIK3CA protein responsible for this rare disease and thus alleviating the symptoms.
In 2016, the doctors obtained authorisation to test the molecule in severe patients resistant to other treatments, particularly surgery. In 2018, the French team published a study in Nature in which they reported the extraordinary efficacy of alpelisib in 19 patients followed at the Hôpital Necker-Enfants malades AP-HP [1].
... paving the way for a marketing authorisation
These results were then confirmed by the retrospective EPIK-P1 study, carried out on 57 patients, 44 of whom were followed at the Necker Enfants Malades hospital [2],[3] which led the FDA to authorise the treatment. Since then, just over 150 patients have been treated with this molecule at Necker Enfants Malades Hospital.
For Pr Guillaume Canaud. "This is a major step forward in improving patient care."
For Christine Clerici, President of Université Paris Cité: "This is first of all excellent news for patients suffering from Cloves syndrome who will finally be able to benefit from a treatment thanks to this major decision by the FDA. It is also, on behalf of the international scientific community, an important mark of recognition of the quality of French research and teaching, which are the bearers of innovation!"
For Gilles Bloch, CEO of Inserm: "This announcement not only crowns the work of excellence carried out by a French team combining basic and clinical research, but also demonstrates the capacity for innovation resulting from the research that the Institute carries out with its partners. It is also, and above all, great news for patients, offering them the hope of a better quality of life."
For Martin Hirsch, Director General of the AP-HP: "From fundamental research to the arrival of a new treatment for rare diseases, this authorisation is the culmination of an exemplary partnership and an inspiring approach that we would like to encourage."
In Europe, marketing authorisation will take a little longer due to a randomised clinical trial that is still ongoing.
References :
[1] Venot, Q., et al. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature 558, 540–546 (2018). https://doi.org/10.1038/s41586-018-0217-9
[2] Canaud G, et al. - EPIK-P1: Retrospective Chart Review Study of Patients With PIK3CA-Related Overgrowth Spectrum Who Have Received Alpelisib as Part of a Compassionate Use Programme / Presented at the 2021 ESMO Congress; September 17-21, 2021.
[3] Morin, G, et al., Treatment of two infants with PIK3CA-related overgrowth spectrum by alpelisib. J Exp Med (2022) 291 (3). https://doi.org/10.1084/jem.20212148
For more information :
Read the Inserm and AP-HP press releases