FDA nod for combination therapy boosts GlaxoSmithKline in melanoma.
By Dominique Fontanilla, Senior Analyst
10 January 2014
I joined Datamonitor Healthcare’s disease team in 2014 having previously worked as a biochemistry postdoctoral fellow ...
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On 9 January 2014, GlaxoSmithKline announced that a combination of Mekinist (trametinib) and Tafinlar (dabrafenib) had received accelerated approval from the FDA for the treatment of BRAF V600E and V600K mutation-positive melanoma.
This is the first FDA-approved combination of targeted therapies for malignant melanoma, and represents a substantial improvement over the monotherapy drugs available in the current melanoma market. While still dependent on Phase III trial results, this accelerated approval comes in advance of Roche’s proposed combination therapy of Zelboraf (vemurafenib) and cobimetinib (GDC-0973), which is being investigated in Phase III trials. Having achieved first-to-market status, the combination of Mekinist and Tafinlar is expected to gain significant uptake in first-line malignant melanoma treatment.
The accelerated approval was based on results from a Phase II study evaluating response rate and duration of response. In a sample of 54 patients, the overall response rate was 76% in those treated with the combination therapy compared with 54% in patients treated with Tafinlar alone. The median duration of response was 10.5 months in patients treated with the combination therapy, compared with only 5.6 months in patients treated with Tafinlar as a monotherapy.
An important point of differentiation for GlaxoSmithKline’s combination therapy is that patients receiving Tafinlar and Mekinist do not seem to develop resistance. This will likely threaten Zelboraf’s revenues in the market; indeed, previous studies demonstrated that patients developed resistance to single-agent Zelboraf after five to seven months of treatment. Furthermore, as the combination therapy uses a strategy of simultaneously targeting both the BRAF and MEK signaling pathways, it has proven to be more clinically effective than a monotherapy approach.
Mekinist and Tafinlar have had limited success in competing with Zelboraf following their approvals as single agents for the first-line treatment of metastatic BRAF V600 mutation-positive melanoma in May 2013. However, in light of the regulator’s decision, Datamonitor Healthcare expects that the two drugs will gain significant uptake as part of the combination therapy. Total sales of both drugs are forecast to reach $459m by 2021 in the US, Japan, and five major EU markets (France, Germany, Italy, Spain, and the UK), allowing GlaxoSmithKline to better compete with Roche in the malignant melanoma market.