AstraZeneca Sells Rights to Two Cardiovascular Drugs for $400 Million

By: Jennifer Galvet, PharmD Candidate c/o 2024

Introduction

The British-Swedish multinational pharmaceutical and biopharmaceutical company AstraZeneca has agreed to sell its rights to two cardiovascular drugs to Germany’s Cheplapharm Arzneimittel GmbH for $400 million. This decision allows AstraZeneca to reinvest in the company’s main areas of focus: cardiovascular, renal and metabolism, cancer, respiratory, inflammation and autoimmunity, infection and vaccines, and neuroscience. ¹ As of recently, AstraZeneca also has a potential COVID-19 vaccine in late-stage clinical testing. ¹

Atacand and Atacand Plus Therapy

On October 30, 2020, AstraZeneca sold the commercial rights to Atacand® (candesartan cilexetil) and Atacand Plus® (a fixed dose combination of candesartan cilexetil and hydrochlorothiazide) to Cheplapharm. Candesatan cilexetil is a prodrug that is hydrolyzed to candesartan during absorption from the gastrointestinal tract. Candesartan is a selective AT 1 subtype angiotensin II receptor antagonist, indicated for the treatment of hypertension and heart failure in patients with left ventricular systolic dysfunction to reduce cardiovascular death and heart failure hospitalizations^{. 5} Angiotensin II is created from angiotensin I in a reaction catalyzed by an enzyme known as ACE, or angiotensin-converting enzyme. Angiotensin II is the principal antihypotensive agent of the renin-angiotensin system, affecting vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. ⁵ Candesartan inhibits the vasoconstriction and aldosterone releasing effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT I receptor. This receptor is located in many different tissues, including the adrenal glands and vascular smooth muscle. Restriction of the angiotensin system with ACE inhibitors (resulting in the inhibition of the biosynthesis of angiotensin II from angiotensin I), is used in the treatment of hypertension.⁵

Candesartan cilexetil and hydrochlorothiazide has been widely used to treat hypertension. Hydrochlorothiazide acts on the distal convoluted tubules of the kidneys and inhibits the sodium chloride co-transporter system. ³ This results in diuretic action and loss of potassium in the urine. Hydrochlorothiazide is indicated as adjunctive therapy to treat edema associated with congestive heart failure, hepatic cirrhosis, corticosteroid and estrogen therapy, and renal dysfunction, in addition to its indication for treatment of hypertension^{. 3} Thiazide diuretics increase the excretion of sodium, chloride, and water by inhibiting sodium ion transport across the renal tubular epithelium. The major mechanism responsible for diuresis is inhibition of active chloride reabsorption at the distal portion of the distal convoluted tubule. When administered acutely, hydrochlorothiazide lowers blood pressure by decreasing cardiac output and decreasing plasma and extracellular fluid volume flowing through a person’s arteries and veins. Chronic use of hydrochlorothiazide reduces blood pressure by decreasing peripheral resistance, or the resistance of the arteries to blood. ³ Essentially, this medication is responsible for removal of sodium and water from the body, thus reducing blood pressure. Candesartan cilexetil and hydrochlorothiazide is indicated for the management of hypertension when monotherapy with either candesartan or hydrochlorothiazide is insufficient.²

How will this affect AstraZeneca?

Both Atacand® and Atacand Plus® are commercially available in approximately 70 countries. Ruud Dobber, Ph.D, the executive vice president of AstraZeneca’s biopharmaceuticals business unit, explained that the agreement to sell the commercial rights to Cheplapharm Arzneimittel GmbH is part of the company’s strategy to carefully manage its mature medicines and focus on its main therapy areas. ^1,2,4 This also includes utilizing the proceeds from the $400 million sale for reinvestment in these main therapeutic areas. AstraZeneca will continue to manufacture both hypertension medications during a three year transition period. ² When the agreement is finished in the fourth quarter of this year, Cheplapharm Arzneimittel GmbH will compensate AstraZeneca $250 million, and then remaining $150 million in the first half of 2021. ^1,2,4  This agreement will allow Cheplapharm Arzneimittel GmbH to expand the reach of these cardiovascular medications into additional countries_. ¹

 This agreement will allow for funding of innovative new medications for patients and continued access of these important cardiovascular medications for patients worldwide. The continued patient access to candesartan cilexetil and candesartan cilexetil and hydrochlorothiazide will reduce the risk of fatal and non-fatal cardiovascular events such as strokes and myocardial infarctions associated with hypertension on a global spectrum.

Sources:

1. George J. AstraZeneca sells the rights to two hypertension drugs in $400M deal. Philadelphia Business Journal. https://www.bizjournals.com/philadelphia/news/2020/11/02/astrazeneca-wilmington- hypertension-drug-atacand.html. Published 11/02/2020.
2. Keown A. AstraZeneca divests rights to two cardiovascular drugs for $400 million. BioSpace. https://www.biospace.com/article/astrazeneca-sells-rights-to-cardiovascular- drugs-for-400-million/. Published 10/30/2020.
3. Kaweah Delta HCD Emergency Med Residency Creighton University School of Medicine Herman LL(1), Bashir K(2). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020-. 2020 Jul 26. Hydrochlorothiazide.. .
4. Letter T. Cheplapharm buys rights to Atacand in more than 70 countries. thepharmaletter. https://www.thepharmaletter.com/article/cheplapharm-buys-rights- to-atacand-in-more-than-70-countries. Published 10/30/2020.
5. Atacand (candesartan cilexetil) [package insert]. Wilmington, DE; AstraZeneca; Revised 07/08/2020.