Arrowhead Pharmaceuticals now has preliminary evidence for a RNAi treatment therapy that’s going up against Merck in a type of kidney cancer.
Early clinical data shared Wednesday showed that ARO-HIF2 lowers levels of its target protein, encouraging Arrowhead to continue its pursuit of Merck’s near-approval rival therapy in clear cell renal cell carcinoma (ccRCC).
ARO-HIF2 is designed to stop production of HIF2a, a transcription factor linked to the proliferation, progression and spread of tumors. Merck is going after the target with belzutifan, the drug at the heart of its $1.1 billion takeover of Peloton Therapeutics. The Merck drug could win FDA approval by September, but Arrowhead still sees room for its alternative take on tackling HIF2a.
Arrowhead framed the ARO-HIF2 update as positive, although the details are limited. Investors, still reeling from the suspension of the company’s cystic fibrosis clinical trial, drove down the stock price a little.
The data come from 17 heavily pretreated ccRCC patients who received intravenous injections of 225 mg or 525 mg of ARO-HIF2 weekly. Arrowhead has evaluable tumor biopsy material from nine of the patients. HIF2a levels fell in seven of the patients, with the declines ranging from 9% to 82%. The mean reduction was 48%.
Analysts at Jefferies said the data show ARO-HIF2 “is getting into tumor cells and knocking down HIF2, setting a foundation for a solid tumor platform.” The analysts want to see more data to show that HIF2a knockdown drives tumor shrinkage, but the available evidence suggests ARO-HIF2 engages with its target as planned.
Arrowhead has limited data on the clinical consequences of HIF2a knockdown. One patient on 525 mg of ARO-HIF2 had a partial response. Five had stable disease. As of the cutoff, four subjects were still on the drug with treatment durations of 12 to 24 weeks.
With the 525-mg dose being well tolerated, Arrowhead is now enrolling a cohort of subjects that will receive 1050 mg of ARO-HIF2 weekly. Dialing up the dose could increase the number of responses.
Merck has set the bar Arrowhead needs to clear by linking belzutifan to a response rate of 49% in a first-line setting and 22% in relapsed or refractory patients when given in combination with Exelixis’ Cabometyx. The Jefferies analysts see an opportunity for Arrowhead to differentiate on safety, noting that so far ARO-HIF2 is free from the drug-related anemia that affects belzutifan.