With a positive phase 3 trial in hand, Japan’s Daiichi Sankyo plans to file its essential hypertension therapy esaxerenone in its home market next year.
It’s a big step forward for the company’s 11-year partnership with Exelixis on drugs that target the mineralocorticoid receptor (MR). It sets the U.S. biotech on course for a third product approval that it says could generate “substantial” milestones plus low-double-digit royalties on sales. The start of the phase 3 trial last year prompted a $15 million milestone payment.
Despite a large number of available drugs, most people with high blood pressure don’t manage to reach treatment goals. Mineralocorticoids play an important role in regulating blood pressure, primarily through control of sodium reabsorption in the kidney, but older drugs in the class such as spironolactone and eplerenone suffer from side effects, poor selectivity and low potency.
Esaxerenone (CS-3150)—a nonsteroidal, selective MR antagonist—is being positioned as a better alternative to the older drugs, and in the latest trial met its primary objective of matching eplerenone for blood pressure-lowering activity with no safety concerns, Exelixis said.
Spironolactone and eplerenone are also not recommended for use in patients with diabetic nephropathy because of a risk of high blood potassium (hyperkalemia), which is a limitation as diabetes and hypertension often go hand-in-hand. Esaxerenone may not suffer from that impediment, and in fact Daiichi Sankyo has just started phase 3 trials of esaxerenone in diabetic nephropathy.
For now, Daiichi Sankyo is focused primarily on the Japanese market, not least because hypertension is common in Japan and impacts approximately 43 million patients, only 30% to 40% of whom are adequately controlled by current antihypertensive therapies.
Elsewhere, Bayer looks to be in front with its finerenone candidate, another nonsteroidal MR antagonist that promises to improve on the older drugs and is in phase 3 testing for diabetic nephropathy.
Shares in Exelixis took a tumble last week for no clear reason other than a possible market correction, as the stock has been gathering breakneck momentum over the last three years thanks to the prospects for second-line kidney cancer therapy Cabometyx (cabozantib) and Roche-partnered Cotellic (cobimetinib) for lung cancer.
Currently in the mid $20s, it was down below $1.50 around the end of 2014. News of the positive esaxerenone trial prompted a 2% uptick in after-hours trading, and could well renew speculation that the company is a potential takeover candidate, particularly with positive data in hand from the CABOSUN trial of Cabometyx in first-line kidney cancer.