Novartis Cancer Pipeline Looks Very Promising


Swiss drugmaker, Novartis has been working dedicatedly against the deadly BRAF-mutation positive version of advanced melanoma and non-small cell lung cancer (NSCLC). Recently, they presented related promising data in 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.

Tafinlar + Mekinist in lung cancer

Novartis pharma logoNovartis’ combination therapy, Tafinlar® plus Mekinist® administered to the patients with BRAF V600E/K mutation-positive advanced melanoma in Phase III study as a first-line-treatment showed survival rate of 44% after three years. This clinical study was one of the longest survival follow up in patients with BRAF mutation positive melanoma. 26 patients who were switched to the combination therapy from monotherapy also showed significant overall survival (OS). The three-year progression free survival rate was 22% versus 12% in monotherapy patients.

dabrafenib-trametinib novartis

Novartis is committed to improving outcomes for advanced melanoma patients, and we are gratified to see that these data show that we are extending the lives of many patients receiving therapy with Tafinlar + Mekinist,” said Alessandro Riva, MD, Global Head, Oncology Development & Medical Affairs. “This data is also a strong example of the importance of rationally combining targeted therapies and identifying those patients who are likely to benefit from our medicines beyond three years. This type of treatment approach is not only helping to grow the practice of precision oncology, but has the potential to fundamentally change the way we treat cancer”.

BRAF is a human gene which is responsible for the formation of a protein B-Raf which transmits chemical signals to cell nucleus from outside. Various mutations in BRAF gene can cause human cancer.In a wide domain of cancers, BRAF mutations are found. Tafinlar (dabrafenib) is an oral BRAF kinase inhibitor of mutated B-Raf protein used as a targeted therapy to prevent the growth and spread of malignant cells in the body. 

pharmacology of braf in lung cancer

Figure 1. Molecular mechanism of dabrafenib and trametinib (Photo credit: Rosewell Park Cancer Institute).

Mekinist (trametinib) is an oral MEK (mitogen-activated protein kinase) enzyme inhibitor used for treatment of BRAF-mutation positive unresectable or metastatic melanoma.

The combination therapy also demonstrated significant results in a pivotal Phase II study on 57 patients with BRAF V600E mutation-positive metastatic non-small cell lung cancer (NSCLC) who had failed at least one line of chemotherapy. The median Duration of Response (DoR) and Progression-Free Survival (PFS) were 9 months and 9.7 months respectively in the patients which were quite substantial compared to chemotherapy. 63% patients demonstrated clinical response.

Novartis other candidates for NSCLC also featured their encouraging data in ASCO. INC280 (capmatinib) showed promising initial activity in its Phase I as a single agent as well as in combination therapy. Zykadia® (ceritinib) initial results also looked good.

Lung cancer is the number one cause of cancer death world-wide, and more than half of NSCLC patients’ tumors occur as a result of a genetic mutation,” said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. “Novartis is fully committed to bringing forth new, targeted options for NSCLC patients, many of whom remain underserved by today’s available therapies“.

After achieving the significant amount of promising clinical data, Novartis will head for the US regulatory approval for its NSCLC candidate.

Last year in November, Roche’s Cottelic plus Zelboraf® won European Commission approval for treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation. In the 2016, ASCO meeting Genentech (member of Roche’s group) with Exelixis presented results for Cottelic® (Cobimetinib) in combination with other therapy for treatment of BRAF-mutant advanced melanoma.

Recently, Merck partnered with Array BioPharma and Pierre Fabre to initiate Phase III trial for BRAF-mutant metastatic colorectal cancer (mCRC).

The strong pipeline of Novartis for advanced melanoma and aggressive lung cancer-NSCLC shows the serious commitment of Novartis for treatment of BRAF-mutant cancer and seems soon they would be able to achieve a regulatory approval for one.

Featured image credit: Conceptual image of green tree shaped like human lungs © Sergey Nivens (Stock Photo ID: 81093914)

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