Novartis breakthrough leukemia drug Glivec® (imatinib) receives positive opinion from CPMP, moves closer to EU approval

30-Jul-2001

Novartis announced today that it has received a positive opinion from the Committee for Proprietary Medicinal Products (CPMP) for the novel agent Glivec (imatinib) Outside the US: Glivec® (imatinib); in the US: Gleevec™ (imatinib mesylate) in the treatment of adult patients with Philadelphia chromosome (bcr-abl) positive chronic myeloid leukemia (CML) in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis. The European Union (EU) Commission usually grants approval of products four months after a CPMP positive opinion. Glivec was designated orphan drug status in February 2001.

"Novartis is extremely gratified that Glivec, which has already benefited thousands of CML patients worldwide, is now one step closer to becoming readily available to patients in the European Union," said David Epstein, President, Novartis Oncology.

To date, Novartis has received marketing clearance for Glivec in more than 10 countries, including the United States, Switzerland, Argentina, Guatemala, Jordan, Korea, Mexico, Peru and Syria.

The application for marketing authorization was based on Phase I and Phase II data from more than 1000 patients participating in a global clinical trials programme. The effectiveness of Glivec was measured in terms of haematologic and cytogenetic response rates. In chronic phase CML, patients previously failing interferon-alpha therapy, the updated data confirm near complete, durable hematologic responses in more than 90% of patients, with more than half achieving a complete or near complete disappearance of the Philadelphia chromosome in the bone marrow. Patients in the accelerated phase of the disease have continued high levels of hematologic responses, with good cytogenetic response rates for this population of patients. Blast crisis patients continue to demonstrate rapid hematologic blood count responses which are sustained in nearly a third of the responders.

Glivec is one of the first oncology drugs that validates rational drug design based on the understanding of how cancer cells work. Novartis took the significant risk of scaling-up manufacturing and expediting the clinical development when the first evidence of the potential activity of Glivec became apparent. The first submissions for marketing authorization were filed only 32 months after the first dose in man. This timeline more than halved the typical drug development timeframe of approximately six years.

CML is a hematologic stem cell disorder caused by an abnormality in the DNA of the stem cells in bone marrow. This results in a gene that produces an abnormal protein. The protein disrupts the bone marrow's normally well-controlled production of white blood cells and results in a massive increase in the concentration of white blood cells in the blood. CML progresses through three phases – chronic, accelerated and blast crisis. After about five years of the chronic, or most common phase, the disease develops eventually into the advanced stages – accelerated then end-stage or "blast crisis"—which usually results in the death of patients in two to six months.

The majority of patients treated with Glivec experienced adverse events at some time. Most events were of mild to moderate grade and treatment was discontinued for adverse events only in 1% of patients in chronic phase, 2% in accelerated phase and 5% in blast crisis. Glivec is contraindicated in patients with known hypersensitivity. Women of childbearing potential should be advised to avoid becoming pregnant. If Glivec is used during pregnancy or if the patient becomes pregnant while taking Glivec, the patient should be apprised of the potential hazard to the fetus. The most common side effects included nausea, fluid retention, muscle cramps, diarrhea, vomiting, hemorrhage, musculoskeletal pain, skin rash, headache, fatigue, arthralgia, dyspepsia and dyspnea, as well as neutropenia and thrombocytopenia.

https://www.chemeurope.com/en/news/4092/novartis-breakthrough-leukemia-drug-glivec-imatinib-receives-positive-opinion-from-cpmp-moves-closer-to-eu-approval.html