Merck/Pfizer up the pressure on BMS in first-line kidney cancer

The FDA has started a speedy review of Merck KGaA and Pfizer’s new combination regimen for advanced kidney cancer, setting up a possible approval in June and piling more pressure on Bristol-Myers Squibb.

The two companies have filed their partnered PD-L1 inhibitor Bavencio (avelumab) with Pfizer’s tyrosine kinase inhibitor Inlyta (axitinib) for patients with advanced renal cell carcinoma (RCC), the most common form of kidney cancer.

The marketing application is based on the JAVELIN Renal 101 trial, which was reported at last year’s ESMO conference and revealed an objective response rate (ORR) of 55% with the duo compared to 26% with Pfizer’s older targeted drug Sutent (sunitinib), with progression-free survival (PFS) of 13.8 months and 8.4 months, respectively.

At the moment BMS has carved out a strong position in first-line RCC with its PD-1 inhibitor Opdivo (nivolumab) and CTLA4 inhibitor Yervoy (ipilimumab), which was approved last year in the US and earlier this year in Europe. According to BMS the combo is fast becoming the standard of care in the US, and first-line RCC – along with adjuvant melanoma – were the drivers of Opdivo’s sales growth last year.

Bavencio and Inlyta are just one rival therapy threatening that position. This week, Merck & Co/MSD reported new results from the phase 3 KEYNOTE-426 study which showed that the combination of its PD-1 inhibitor Keytruda (pembrolizumab) with Inlyta reduced the risk of death in RCC by around 47% compared with Sutent.

That could overturn one key defence for Opdivo/Yervoy  in previously-untreated patients, namely its more mature overall survival data that has driven uptake to date, and the bad news for BMS is that Merck has already filed for approval of its dual regimen with the FDA.

Analysts have suggested that Merck’s results are stronger as they were seen in a broader patient population than Opdivo/Yervoy, which saw the most benefit in intermediate- and high-risk patients, so Merck could start eating into BMS’ market share after approval.

That could allow Merck to press home its advantage, building on its dominant position in the lucrative first-line non-small cell lung cancer (NSCLC) indication where Opdivo has failed to generate convincing trial results.

So where does that leave Bavencio and Inlyta? One question is whether Merck KGaA and Pfizer’s existing collaboration will make them better placed to market their combination if it gets approved, or whether Merck’s strength in immuno-oncology will make it worth Pfizer’s while to ride that success with the Inlyta combination.

Either way, the outlook for patients with advanced RCC remains poor despite available therapies, particularly as approximately 20% to 30% of patients already have metastatic disease at diagnosis, so having multiple new therapies coming through the pipeline is good news for patients. As it stands, the five-year survival rate for patients with metastatic RCC is only around 12%.