Entrectinib, the kinase inhibitor drug that was initially discovered and developed by Nerviano Medical Sciences (a member of NMS Group) and that is now marketed by Roche and partners, has received approval for marketing and reimbursement from the Italian drug agency AIFA in two oncology indications: lung cancer ROS1 kinase fusion positive, and any solid tumor type with NTRK kinase gene fusions.
Entrectinib was originally invented and developed into a drug product at Nerviano. It is highly active against tumors with rearranged forms of either one of the three kinases called ALK, ROS, and TRK, and its initial Phase I study, which started in 2012, was conducted at two major hospitals in Milan – the IRCCS Istituto Nazionale dei Tumori (INT) and the Niguarda Cancer Center. This first-in-human (FIH) study generated some of the key data later used to obtain worldwide marketing approval of the drug in the two different oncological indications, with patient selection based on molecular defects in the NTRK and ROS genes.
Entrectinib, designed to efficiently cross the blood brain barrier in order to treat ROS1-rearranged lung cancer patients with CNS metastases, demonstrated a high level of efficacy in such patients – a key factor for its approval in this type of cancer. Also, with entrectinib NMS provided the first clinical evidence that NTRK gene fusion products, present at a low but significant frequency in several different tumor types, represent a druggable target for solid tumors – a finding which later led to the marketing approval of one of the first precision medicine drugs to receive an agnostic indication (approval for use against any type of tumor with a given genetic context and independently from the tissue origin), i.e. that for use against NTRK rearranged solid tumors.
The success of the Phase I clinical study of entrectinib initiated by NMS led to a collaboration with the biotech Ignyta, who continued clinical development of the drug in a global Phase II registration trial, prior to being acquired by Roche. Receiving several regulatory authority approvals between 2019 and 2020 in various major geographic regions, entrectinib is now marketed worldwide by Roche and partners. We are very pleased to acknowledge that on 14 September 2021 the Italian drug regulatory agency AIFA approved entrectinib for marketing and reimbursement in its homeland.
Link to the Roche press release in Italian: Tumori: è made in Italy la terapia intelligente | Roche Italia
PR: Entrectinib AIFA approval 14092021