Novartis announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has issued a positive opinion for the use of Glivec (imatinib) as a treatment for the solid tumour dermatofibrosarcoma protuberans (DFSP) and for haematologic malignancy Philadelphia chromosome-positive (Ph+) acute lymphocytic leukaemia (ALL).
The committee's recommendation will now be considered by the European Commission, which is expected to issue a final decision within the coming months. The European Commission generally follows the recommendations of the scientific committee in its decisions.
Submissions for three other rare diseases - myeloproliferative disorders (MPD), hypereosinophilic syndrome (HES) and systemic mastocytosis (SM) - remain under review by the committee. Applications for marketing authorization of Glivec as a treatment for all five diseases have been submitted to and are currently under review by the US Food and Drug Administration. Glivec is already approved for the treatment of adult patients in all phases of Ph+ chronic myeloid leukaemia (CML) and for patients with unresectable and/or metastatic Kit (CD117)-positive gastrointestinal stromal tumours (GIST).
Both DFSP and Ph+ ALL are rare and potentially-life threatening diseases. Few, if any, approved treatments are available for many patients suffering from these diseases. DFSP is a type of tumour that begins as a hard lump found in the skin of the chest, abdomen or leg. Ph+ ALL is a rapidly progressive and life threatening blood cancer.
"We are now finding that cancers and diseases of different origin and location can share common pathways that often respond to the same targeted treatment," said Diane Young, vice president and global head of Clinical Development at Novartis Oncology. "The positive CHMP opinion is hopeful news for patients who suffer from these rare diseases and have limited treatment options."
Glivec targets the activity of proteins called tyrosine kinases that appear to play important roles within some cancer cells. Glivec has been shown to inhibit the function of the tyrosine kinase Bcr-Abl in Ph+ CML and Ph+ ALL, and the receptor tyrosine kinase Kit in Kit (CD117)-positive GIST. Researchers have found that Glivec also inhibits other tyrosine kinases, including platelet-derived growth factor receptor (PDGFR), which have been shown to be activated in disease pathways that underlie a number of rare haematologic diseases as well as some solid tumours.
The positive opinion was based on data from Novartis-sponsored clinical studies and clinical data from independent medical researchers showing efficacy of Glivec in the treatment of these diseases, in which there is a suggested connection between a Glivec-sensitive pathway and a disease.
Glivec is approved in more than 90 countries including the EU, US and Japan for the treatment of all phases of Ph+ CML. Glivec is also approved in the EU, US and other countries for the treatment of patients with Kit (CD117)-positive GISTs, which cannot be surgically removed and/or have already spread to other parts of the body (metastasized). In Japan, Glivec is approved for the treatment of patients with Kit (CD117)-positive GISTs.
The effectiveness of Glivec is based on overall haematologic and cytogenetic response rates and progression-free survival in Ph+ CML, and objective response rates in Kit (CD117)-positive GISTs. There are no controlled trials demonstrating increased survival.