Although the clinical promise of cancer immunotherapies looks poised to see these products gain a dominant foothold in the oncology market for decades to come, developers of alternative cancer treatments will be hoping to carve out their own share of revenues – most feasibly by targeting subsets of patient populations.
One such opportunity exists in the malignant melanoma market, where between 40 percent and 50 percent of patients are diagnosed with the V600 BRAF mutation.
Roche – the recognised global leader in personalised cancer medicine – was the first to develop a marketed therapy to specifically treat these patients; approved in 2011, the Swiss company had previously in-licensed the BRAF inhibitor Zelboraf from Plexxikon in 2006.
Zelboraf became the first new therapy for malignant melanoma to be approved by the FDA for many years. Its route to market was accelerated not only by the poor prognosis and median survival time (less than a year) among these patients, but development alongside a companion diagnostic from Roche that helped to both shorten clinical trial programmes and define relevant patients. In Phase III studies, Zelboraf demonstrated a median progression-free survival (PFS) of 5.3 months (versus 1.6 months for dacarbazine).
Earlier this week, Roche announced that Phase III studies of Zelboraf in combination with a second therapy – the MEK inhibitor cobimetinib (being co-developed with Exelixis) – had delivered positive top-line data versus Zelboraf alone. With regulatory filings expected later this year, approval for the combination is earmarked for the second half of 2015. See ViewPoints: Roche sets up face-off with Novartis via positive melanoma data.
In the meantime, however, GlaxoSmithKline is already marketing its own combination of MEK and BRAF inhibitors (Mekinist and Tafinlar), which was approved by the FDA in January, and is in the process of being sold to Novartis (along with the remainder of GlaxoSmithKline's oncology pipeline – see ViewPoints: GlaxoSmithKline, Novartis embrace home comforts via innovative $25 billion deal).
Phase III data supporting the use of Mekinist and Tafinlar has its limitations (the COMBI-d study demonstrated PFS of 9.3 months), but based on prescription data the combination appears to be gaining notable traction among oncologists in the US, according to analysts at Bloomberg Industries.
There is some expectation that the data for Roche's combination will be superior (Phase I data delivered PFS of 13.7 months), but with launch at least a year away, GlaxoSmithKline (and shortly Novartis) have time to push home their first-to-market advantage.
If the arrival of Roche's combination is one future dynamic in the BRAF V600 melanoma space, the other is the potential future treatment of patients with immunotherapy, possibly led by a combination of Bristol-Myers Squibb's already approved Yervoy franchise with its late-stage PD-1 inhibitor nivolumab. Will small molecular targeted therapies retain a significant presence in the long term?
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In light of these dynamics – and the clinical update regarding Roche's combination this week – FirstWord is polling US-based oncologists to assess their current treatment choices for BRAF V600 mutation-positive melanoma. Specifically we are asking them...
What percentage of advanced melanoma patients are currently tested for the BRAF V600 mutation?
Which therapy – or combination – they use most frequently to treat BRAF V600 mutation-positive melanoma patients?
Which therapy – or combination – they expect to be using most frequently in 12 months time?
What factor – if any – has prevented them from using the Mekinist/Tafinlar combination?
Whether they expect immunotherapies to assume a dominant first- or second-line position in the future treatment paradigm?