Exelixis’ Collaborator Daiichi Sankyo Announces Positive Results From Phase 3 Pivotal Trial of Esaxerenone in Patients With Diabetic Nephropathy

— Results being presented today in a late-breaking presentation (abstract TH-PO1201) at Kidney Week 2019, the annual meeting of the American Society of Nephrology in Washington, D.C.

ALAMEDA, Calif.–(BUSINESS WIRE)–Exelixis, Inc. (Nasdaq: EXEL) announced today that its partner Daiichi Sankyo Company, Limited (“Daiichi Sankyo”) has reported positive results from a phase 3 pivotal trial of esaxerenone, a product of the companies’ prior research collaboration, in patients with diabetic nephropathy.

Esaxerenone is a novel mineralocorticoid receptor (MR) blocker identified during the prior research collaboration between Exelixis and Daiichi Sankyo and subsequently developed and commercialized by Daiichi Sankyo. Esaxerenone has been approved as a treatment for patients with hypertension in Japan, where it is marketed as MINNEBRO^® tablets. Daiichi Sankyo is solely responsible for esaxerenone’s development and commercialization, with Exelixis remaining eligible for substantial commercialization milestones, as well as low double-digit royalties on sales, as it advances.

“The ESAX-DN study is the second successful phase 3 pivotal trial our collaborators at Daiichi Sankyo have undertaken since assuming responsibility for esaxerenone’s development and commercialization,” said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. “We congratulate our colleagues on a well-run trial in diabetic nephropathy, one of the most significant complications for patients with diabetes, which is itself a major health issue in Japan. We look forward to Daiichi Sankyo’s continued progress with esaxerenone.”

Conducted in Japan, ESAX-DN is a phase 3 randomized, double-blind, two-armed parallel group comparison study of esaxerenone versus placebo in 455 patients with incipient diabetic nephropathy^* who are taking an angiotensin II blocker (ARB) or angiotensin converting enzyme (ACE) inhibitor. The primary endpoint of the study is the rate of remission of microalbuminuria after 52-week treatment, and secondary endpoints include change in rate of urinary albumin to creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR).

The study showed that the esaxerenone-based regimen resulted in a significantly higher UACR remission rate^† (22.1% versus 4.0%) as compared to placebo. The esaxerenone-based regimen also significantly reduced UACR (-58.3% versus +8.3%) and was associated with a significant reduction in progression from incipient to overt diabetic nephropathy^‡ as compared to placebo (1.4% versus 7.5%).

Investigators reported that no new safety concerns were identified in the study. In the esaxerenone group, 8.8% of patients had hyperkalemia as compared to 2.2% of patients in the placebo group; levels recovered after the administration period.

About Diabetic Nephropathy in Japan

Diabetic nephropathy is one of the most significant long-term complications in terms of morbidity and mortality for individual patients with diabetes. In Japan, approximately 10 million people, or 12.1% of the population, are estimated to have diabetes, with a growing incidence. Approximately 50% of all type 2 diabetics will develop evidence of diabetic nephropathy.¹ It is the leading cause of dialysis (42.5%, 2017) in Japan.²

Multifactorial intensive therapy, including control of blood glucose, lipid, and blood pressure and using ARB or ACE inhibitor are recommended in the several treatment guidelines for suppressing the onset and progression of early diabetic nephropathy.^3,4,5 However, these traditional therapies are suboptimal and there is a clear, unmet need for additional treatments.⁶

The progression to advanced stages of diabetic nephropathy is associated with increased risk of dialysis and cardiovascular events. The effect of medication on the suppression of diabetic nephropathy at the advanced stage is not clear. In order to diminish the deterioration of kidney function, it would be desirable to promote remission to normoalbuminuria in diabetic nephropathy in early stages of the disease.^{7, 8}

About Esaxerenone in Diabetic Nephropathy

Esaxerenone is an orally administered, non-steroidal, selective blocker of MR. As recently reported, aldosterone is regarded as a potent mediator of organ damage. Esaxerenone may have a role in preventing these organ damaging effects.

About Exelixis

Founded in 1994, Exelixis, Inc. (Nasdaq: EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX^® (cabozantinib), COMETRIQ^® (cabozantinib), COTELLIC^® (cobimetinib) and MINNEBRO^® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of Standard & Poor’s (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

Forward-Looking Statements

This press release contains forward-looking statements, including, without limitation, statements related to: Exelixis’ eligibility for substantial commercialization milestones as well as low double-digit royalties on the sale of MINNEBRO; the potential for further progress in MINNEBRO’s clinical development and commercialization; and Exelixis’ plans to reinvest in its business to maximize the potential of the company’s pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the availability of data at referenced times; risks and uncertainties related regulatory review and approval processes and Daiichi Sankyo’s compliance with applicable legal and regulatory requirements; uncertainties inherent in the product development process; the degree of market acceptance of MINNEBRO in the territories where it is approved, and Daiichi Sankyo’s ability to obtain or maintain coverage and reimbursement for this product; Exelixis’ dependence on its relationship with Daiichi Sankyo, including Daiichi Sankyo’s investment in the resources necessary to successfully commercialize MINNEBRO in the territories where it is approved; market competition, including the potential for competitors to obtain approval for generic versions of MINNEBRO; Exelixis’ and Daiichi Sankyo’s ability to protect their respective intellectual property rights; changes in economic and business conditions; and other factors affecting Exelixis and its partnerships discussed under the caption “Risk Factors” in Exelixis’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on October 30, 2019, and in Exelixis’ future filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein.

Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a registered Japanese trademark.

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Definitions of Terms

^* Incipient diabetic nephropathy means type 2 diabetes with microalbuminuria, 45≦UACR＜300 mg/g Cr in this study.

^† Satisfying both reversal to normal range of UACR, which is an index of kidney function, and sustainment; defined as achieving two consecutive UACR <30 mg/g Cr (normoalbuminuria) values at the end of treatment, and 30% reduction of UACR from baseline.

^‡ Overt diabetic nephropathy is defined as type 2 diabetes with UACR which is increased to equal or more than 300 mg/g Cr

References

¹ Parving HH, et al., Prevalence and risk factors for microalbuminuria in a referred cohort of type II diabetic patients: a global perspective. Kidney Int 69:2057-2063, 2006.

² Nitta K, et al., An overview of regular dialysis treatment in Japan as of Dec. 31, 2017. J Jpn Soc Dial Ther 2018;51(12): 699-766

³ Japanese Society of Nephrology. Evidence-based Clinical Practice Guideline for CKD (2013). Clinical and Experimental Nephrology June 2014, Volume 18, Issue 3, pp 346–423.

⁴ The Japan Diabetes Society. Evidence-based Practice Guideline for the Treatment for Diabetes in Japan 2016

⁵ The Japanese Society of Hypertension. Guidelines for the Management of Hypertension (JSH 2014). Hypertens Research 2014; 37: 253-392.

⁶ Shirakami S. Drug development for unmet medical needs. OPIR Views and Actions 2015;45:30-3.

⁷ Gaede P, Tarnow L, Vedel P, et al., Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria. Nephrol Dial Transplant. 2004 Nov; 19 (11):2784-8.

⁸ Ruggeneniti P, Fassi A, Ilieva AP, et al., Effects of verapamil added-on trandolapril therapy in hypertensive type 2 diabetes patients with microalbuminuria: the BENEDICT-B randomized trial. J Hypertens. 2011 Feb;29 (2):207–16.

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