The recent FDA approval of Exelixis, Inc.’s EXEL Cabometyx for the treatment previously untreated advanced renal cell carcinoma has put the spotlight in this space.
RCC is the most common form of kidney cancer in adults. Per statistics, approximately 30,000 patients in the United States and 68,000 around the world need a first-line treatment for advanced kidney cancer. As many as 14,000 patients need the same annually in the United States.
The approval comes two months ahead of schedule. We note that Cabometyx (cabozantinib), a tyrosine kinase inhibitor, or TKI, was already approved for the treatment of RCC in patients who have already received anti-angiogenic therapy. Cabozantinib inhibits the activity of tyrosine kinases, including MET, AXL, VEGF receptors, and RET. The approval came on the back of results from the randomized phase II, trial CABOSUN. The results demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus the current standard of care, Pfizer Inc.’s PFE Sutent. Importantly, Cabometyx demonstrated a clinically meaningful and statistically significant 52% reduction in the rate of disease progression or death. Median PFS for Cabometyx was 8.6 months versus 5.3 months for Sutent corresponding to a 3.3 month (62%) improvement.
Sutent is widely used as a first-line treatment for RCC along with Novartis AG NVS Votrient. However, the FDA approval of Cabometyx on excellent rates of PFS might weigh on Sutent going forward though Pfizer too is striving hard to retain the drug’s leadership. In November 2017, the FDA approved a label expansion for Sutent. The drug was approved for the adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy (surgical removal of the cancerous kidney). The approval was based on results from the S-TRAC trial that demonstrated a significant reduction in the risk of a disease-free survival event (defined as the interval between randomization and tumor recurrence, or secondary primary cancer or death from any cause) for patients at high risk of RCC recurrence who received Sutent compared to placebo in the adjuvant setting.
Meanwhile, Pfizer’s another drug, Inlyta, a TKI, is also approved for RCC. Bavencio (avelumab), a monoclonal antibody that inhibits PD-L1, in combination with Inlyta is being developed for the first-line treatment of advanced RCC, in collaboration with Merck KGaA MKGAF.
On the other hand, immunotherapies are gearing up too for place in this space. In September 2017, Bristol-Myers Squibb Company BMY announced that a phase III study is evaluating Opdivo plus Yervoy combination in patients with previously untreated advanced or metastatic RCC met its co-primary endpoint. The combination demonstrated superior overall survival (OS) compared to Sutent in intermediate- and poor-risk patients. The combination also met a secondary endpoint of improved OS versus Sutent in randomized patients. Consequently, an independent Data Monitoring Committee has recommended that the trial be stopped early based on a planned interim analysis. Last week, the FDA accepted Bristol-Myers’ supplemental Biologics License Application for priority review of Opdivo plus Yervoy (ipilimumab) to treat intermediate- and poor-risk patients with advanced RCC with an action date of April 16, 2018. The FDA had previously granted Breakthrough Therapy Designation for this application which should expedite the review.
Additionally, a variety of combination therapies being developed for RCC, including Roche’s RHHBY Avastin and Tecentriq. Earlier in the month, Roche announced that the phase III IMmotion151 study met its co-primary endpoint of investigator-assessed PFS and demonstrated that the combination of Tecentriq and Avastin provided a statistically significant and clinically meaningful reduction in the risk of disease worsening or death in patients whose disease expressed the PD-L1 (programmed death-ligand 1: Expression ≥1%) protein compared with Sutent for the first-line treatment of people who have advanced or metastatic renal cell carcinoma (mRCC). Top-line results from the co-primary endpoint of OS are not mature.
Eisai Inc. and Merck MRK are also evaluating the combination of the former’s Lenvima a multiple receptor tyrosine kinase inhibitor (including fibroblast growth factor receptors [FGFR] 1 – 4), in combination with the latter’s anti-PD-1 therapy Keytruda for treatment-naïve and previously treated patients with metastatic clear cell RCC. The combination is being evaluated for first-line use of the combination in the ongoing phase III study, CLEAR. The combination reported encouraging interim results in September 2017.
Hence, we expect investors to keep their focus in this space in 2018 given the stiff competition brewing up.
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