PharmGPS^® Predicts the Impact of
Precision Medicine in NSCLC Treatment

On June 22, 2017, the US FDA approved the two-drug combo of Tafinlar^® (dabrafenib) and Mekinist^® (trametinib) for the treatment of patients with BRAF V600E-positive, advanced or metastatic non-small cell lung cancer (NSCLC). After receiving a green-light from the EMA (February 27, 2017), this duo has now entered the US market based on Phase II study results in which more than 60% of treatment-naive and previously treated patients responded. In 2015, this combination therapy received both orphan and breakthrough designation in lung cancer and in the same year, Novartis acquired them as part of its asset-swap deal with GlaxoSmithKline.

Of the 1.8 million new cases of NSCLC diagnosed each year, approximately 36,000 patients are positive for the BRAF V600E mutation. These tumors are extremely aggressive with no approved targeted therapy; therefore, a high unmet need exists that may be met through the Tafinlar^® and Mekinist^® combination.

Tafinlar^® and Mekinist^®, both kinases within the serine/threonine kinase family, target BRAF and MEK1/2, respectively, and are used in treating NSCLC and melanoma, among other cancers. PharmGPS^® analysis predicted the positive synergism of these two kinases in targeting the BRAF mutation-specific NSCLC subpopulation--now proven in the recently published Phase II trial results described below:

BRAF V600E is the fourth actionable genomic biomarker in metastatic NSCLC -- along with EGFR, ALK, and ROS-1, also approved for targeted therapies. The FDA has also approved the Oncomine Dx Target Test as the first targeted NGS-based, in vitro diagnostic test for NSCLC. This now delivers multiple biomarker results simultaneously from one sample and can be used in the detection of the BRAF V600E mutation.

The combination of Tafinlar^® and Mekinist^® in NSCLC (in addition to melanoma), provides a far superior response in BRAF positive patients compared to current chemotherapeutic treatment options. This duo generated sales of approximately $672 million last year (in melanoma) and with its approval in this NSCLC sub-population, is expected to increase by another $200-350 million annually by 2025.

PharmGPS^® analyses predicted that Tafinlar^® and Mekinist^® in combination would be a big milestone for the lung cancer community, especially for patients with tumors bearing the BRAF V600E mutation. This is the first targeted therapy approved for BRAF mutation bearing tumors in NSCLC and which now also includes additional support from an FDA-approved Dx test. As described above, combination treatment outscored dabrafenib monotherapy and further long-term trials are underway to assess overall survival in BRAF V600E positive patients. The potential of this combination could set a new paradigm of treating BRAF V600E NSCLC patients and identify a new trail of future therapies.

PharmGPS^® highlights these other forerunners which are in Phase II: two BRAF inhibitors: Zelboraf^®(Roche) and Tafinlar^® (Novartis) with positive safety and efficacy results, the ERK1/2 kinase inhibitor, ulixertinib (BioMed Valley Discoveries, Inc.), and the combination CDX-3379 + Zelboraf^® (EGFR-3/HER-3 antagonist + B-raf kinase inhibitor; (Celldex and Roche).