Novartis’ cancer combination Tafinlar and Mekinist has been approved by the EMA for adjuvant treatment of advanced melanoma in order to prevent disease recurrence.
The new indication – the third for the BRAF/MEK inhibitor combination – is an important one for Novartis as it faces increasing competition in the melanoma market from immuno-oncology drugs like Bristol-Myers Squibb’s Opdivo and Merck & Co/MSD’s Keytruda.
The EMA has approved Tafinlar (dabrafenib) and Mekinist (trametinib) for the adjuvant (post-surgery) treatment of stage III melanoma patients with BRAF V600 mutations, following in the footsteps of the US FDA which gave a green light to this indication earlier this year.
Approval is based on the 870-patient COMBI-AD study, which showed that patients who received the combination treatment had a statistically significant improvement in relapse-free survival (RFS) compared with those on placebo.
All told, 38% of patients on the Taf/Mek combination had a relapse or died after the primary data cut-off point of more than two and a half years, compared to 57% of the control group, and that benefit has been maintained beyond three years in later analyses.
Novartis acquired Tafinlar and Mekinist as part of its asset-swap deal with GlaxoSmithKline (GSK) in 2015, and since taking over the drugs has grown sales considerably thanks to additional approvals including a go-ahead last year in BRAF V600-postitive non-small cell lung cancer (NSCLC). Sales in the first half of this year rose by a third to $551m, setting it on course for its first blockbuster year.
Novartis chief executive Vas Narasimhan said during the company’s second-quarter results call that “treating patients earlier in the adjuvant setting will enable us to continue to drive Mekinist and Tafinlar… particularly given the competition that of course has come up in the class.”
Taf/Mek competes directly with Roche’s Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination in melanoma, but has been outselling its rival, particularly after Roche’s duo failed to hit the mark in an adjuvant melanoma study last year.
PD-1 inhibitors Opdivo and Keytruda, which have been steadily moving up the treatment pathway in melanoma, have also emerged as a competitive threat to Taf/Mek, although there is now talk of using the cancer immunotherapies and small-molecule BRAF/MEK pair in combination.
BMS’ drug picked up an FDA approval for adjuvant melanoma therapy last December based on the results of the phase III CheckMate-238 trial, and was recommended for approval in that indication in the EU in June. Meanwhile, Merck filed an application for Keytruda in the US in June as an adjuvant therapy based on the KEYNOTE-054 trial.