Exelixis: Cometriq approval a “transitional” event.
The FDA has approved Exelixis’s Cometriq for the treatment of metastatic medullary thyroid cancer (MTC). Approval in this relatively small indication marks a transitional event in Exelixis’s goal to establish Cometriq as an oncology franchise, with potential entry into the larger and more lucrative prostate cancer market likely to be the next step.
Approval of Cometriq was based upon positive data from the EXAM Phase III pivotal trial, an international, randomized, double-blind study of Cometriq versus placebo in 330 patients with advanced or metastatic MTC. It was found that patients receiving a 140mg daily oral dose of Cometriq lived significantly longer before disease progression than those receiving placebo treatment. The progression-free survival (PFS) of patients in the Cometriq arm was 11.2 months compared with 4.0 months in the placebo arm, and the objective response rate in the Cometriq arm was 28% versus 0% in the placebo arm.
Cometriq is an orally available small-molecule inhibitor of the MET, RET, and VEGFR-2 serine/threonine protein kinases, which are essential in promoting tumor growth, cell survival, and angiogenesis.
Thyroid cancer is a relatively uncommon cancer type. Exelixis has calculated that MTC incidence comprises just 1-2% of total thyroid cancer incidence, and has forecast a small population of 500-700 metastatic MTC patients eligible for first- or second-line Cometriq therapy in the US. In addition, Exelixis expects a similar number of drug-eligible patients in Europe.
The treatment of metastatic MTC still represents a significant area of unmet need. Currently, the only marketed drug available is Caprelsa (vandetanib; AstraZeneca), which received FDA approval in 2011 and EMA approval in 2012. However, the FDA has expressed concern about the high levels of toxicity associated with Caprelsa treatment, including cardiac toxicity. A prominent barrier to the uptake of Caprelsa for MTC therapy is the restriction of access to the drug by the FDA. Physicians require certification through the FDA’s Caprelsa Risk Evaluation and Mitigation Strategy (REMS) program before they can prescribe the drug.
Datamonitor expects the initial uptake of Cometriq will be limited to an exclusive set of patients with progressive metastatic MTC, although there may be additional opportunities for uptake. Physicians may be tempted to prescribe Cometriq preferentially to patients with progressive metastatic disease, while choosing Caprelsa in other metastatic patients. Both drugs displayed good efficacy against metastatic MTC, providing patients with significant PFS benefits compared with placebo.
However, inclusion criteria in the EXAM clinical study of Cometriq specified that patients must be suffering from progressive disease at screening compared with a previous CT scan or MRI image. In contrast, progressive disease was not a mandatory requirement in the Caprelsa Phase III study. As a result, physicians may choose to prescribe Cometriq only in cases of progressive disease because of its demonstrated efficacy in this patient subgroup. Despite this, additional opportunities for uptake may be available in patients previously treated with Caprelsa or in cases where Caprelsa therapy is not possible due to the REMS program restrictions accompanying its use.
The approval of Cometriq in metastatic MTC has the potential to act as a springboard for its approval in the far more lucrative prostate cancer market. Michael Morrissey, Exelixis president and chief executive officer, stated in a press release that the approval of Cometriq was a “transitional” rather than a “transformational” event, and was an “important milestone” in building the Cometriq oncology franchise.
The approval for metastatic MTC will gain Exelixis its first returns on Cometriq, which carries a $9,900 price tag for a 28-day treatment course. However, Exelixis has communicated a clear strategy of pursuing more lucrative indications that could mean bigger financial gain. Cometriq is currently being assessed in the COMET-1 Phase III pivotal study as a therapy for metastatic castration-resistant prostate cancer.
Posted in Company analysis, Oncology. Tagged to Exelixis; Cometriq; Oncology; Transitional; Pipeline