RESEARCH & PROGRESS

The COSY consortium was set up after collaboration from partners working together around the OS in research and clinical care. There are several long-lasting collaborations: between Guillaume (Scientific Coordinator) and Mario Pende (INSERM) who belong to the same research department and are already working together on mouse models. Stéphanie Baulac (Institut du Cerveau – ICM) and Nadia Bahi Buisson (INSERM and Assistance Publique – Hôpitaux de Paris (APHP)) belong to the same network of neuroscientists. Stéphanie Baulac and Christine Bole (Institut Imagine) have been working with IntegraGen in genomics sequencing. Nadia Bahi Buisson and Guillaume Canaud have been collaborating to organize the care of OS patients at Necker Enfants Malades. Laurent Guibaud (Hospices Civils de Lyon – HCL) has been interpreting the imaging of these patients.

Additionally, more recent collaborations have taken place: Guillaume Canaud and Laurent Guibaud have recently started to work together with the partner companies Kitware and EOS Imaging. The project is therefore a joint initiative of 11 partners to re-define a new standard of care and to offer a unique multidisciplinary service organization dedicated to OS patients. It combines all the necessary skills to propose innovative tools in physiopathology, genetics, imaging, and care reorganization. The knowledge and skills of all the PIs and industrial partners, their already established collaboration, and the affinities already developed will provide a unique opportunity to tackle the outcome of OS.

We received mid-April 2022 an excellent news: Alpelisib was approved by the FDA for the treatment of patients with PIK3CA related disorders.

This is for Pr Guillaume Canaud, the coordinator of the RHU COSY, and his group a fantastic achievement. Indeed, they identified Alpelisib as a promising compound for the treatment of overgrowth syndromes in 2016. After promising data were obtained in a mouse model, they rapidly treated the first adult patient followed by a pediatric one and then 17 additional patients. These first results in human were extremely encouraging and published in the renowned scientific journal Nature.

Following the release of the article, a huge number of physicians and patients from all over the world manifested their interest for Alpelisib as a treatment for overgrowth syndromes. To meet the demand, the dedicated unit at Hôpital Necker – Enfant Malades, Paris, France had to be totally reorganized. Indeed, at that time, Pr Canaud’s team was performing patient genotyping daily, data were obtained in 3 weeks and, for all patients, therapeutic opportunities werediscussed in a multidisciplinary team in order to identify patients that could join a clinical trial with Alpelisib.

Thanks to the support of Novartis and several patient advocacy groups, the clinical trial named EPIK-P1 was set up and started in June 2020. Fifty-nine patients with PIK3CA-related overgrowth syndromes were included and received Alpelisib. Effect of Alpelisib was satisfactory with minimal side effects.

Data were presented for the first time on September 2021 at the ESMO meeting in the developmental therapeutic session and then examined by the FDA (US Food and Drug Agency). After few months and two inspections at the Hôpital Necker – Enfant Malades, FDA approved the use of Alpesilib for the treatment of PIK3CA-related overgrowth syndromes.

But this is not the end of the story for Guillaume Canaud and his group, in the meantime they developed new mouse models in order to better understand overgrowth disorders and how Alpesilib works. These data were also published in high impact factor journals such as Science Translational Medicine and Journal of Experimental Medicine.

The word of Guillaume Canaud:

“During the last few years, I had the chance to present our findings in many places and I was always surprised by the warm welcome that I received. All these trips have opened plenty of new collaboration, favored the growth of new projects and helped many patients. I would like to express my deepest gratitude to all our team members (clinical staff and researchers) that are fully dedicated to improve the wellbeing of our patients. I would like to thank the patients for their trust in us, the funding agencies that support us. But also, Editors and Reviewers for helping us to improve our reseach.”

Objectives, progress and highlights of the COZY project in 2020

The overall aim of the COSY project is to improve the medical care of patients with overgrowth syndromes. To this end, we intend to improve the genetic diagnosis; identify new genes involved; understand how the disease develops and progresses; identify new therapeutic targets; improve patient care (one-day-care concept); develop new imaging tools to improve patient’s follow-up; increase awareness of these syndromes within the medical community and promote a better patient integration through dissemination in appropriate communication channels.

The project started nearly at the same time as the global COVID-19 pandemic, however, it did not impact our motivation, and we have been able to move forward despite the international context. In fact, we have identified new genes in OS patients, and we are currently trying to demonstrate their contribution to the development of these syndromes. We have also made progress in understanding the molecular mechanisms of these syndromes, about which several scientific publications will be published soon. A new tool to assess patient bone abnormalities will be delivered later this year as well as new modalities for imaging analysis.

Finally, our hospital care level improved through an increasingly smoother patient journey. This first year allowed us to lay the foundations of our project. The coming year shall see several deliverables being reached. To be continued!