One of Pascal Soriot’s first big decisions after taking over as CEO of AstraZeneca was to take control of a long-standing diabetes alliance with Bristol-Myers Squibb.
The deal signed in 2014 gave AZ full control over what is turning out to be one of its most important drugs – Forxiga/Farxiga (dapagliflozin), an SGLT-2 inhibitor that was initially used as a way of controlling blood sugar in patients with diabetes.
But as science has moved on, it emerged that the drug was far more versatile than this – and data under review by regulators shows it can be used to reduce risk of hospitalisation for heart failure in patients with type 2 diabetes, and even those without diabetes and certain other risk factors.
It is also being reviewed by the FDA to reduce risk of cardiovascular death in heart failure with preserved ejection fraction, and those with reduced ejection fraction, and to prevent worsening of the disease.
With every new indication, sales are mounting, and the versatility of Farxiga in a highly competitive market has set the tone for the rest of the franchise.
Trial results from the DAPA-HF trial released last year were a real turning point, showing the effect of reducing death and hospitalisation in heart failure patients, with or without diabetes, said Joris Silon, head of AZ’s CVRM biopharmaceutical unit.
It’s still not clear exactly how the drug is producing this effect, but the results outlining the versatility of Farxiga form the bedrock of AZ’s strategy to look at CVRM as a series of inter-related diseases.
Silon said: “I think it’s a testament to our people in R&D that have really followed the science, and also taken a risk because at the time we were designing these trials there was no clear proof that this would work.
AZ has not stopped at diabetes – the company is also trying to extend Farxiga’s use into chronic kidney disease.
The FDA has granted Fast Track designation for the development of Farxiga in this extended use, meaning AZ will get extra support during development, and a faster six-month review of trial results if things go to plan.
“If that delivers we will have created multiple indications within one brand, we will be working in prevention for type 2 diabetes patients for cardio-renal diseases, but it will also treat cardio-renal diseases and I don’t think there are so many classes out there that can have that.”
But AstraZeneca will have competition, as it’s not the only SGLT-2 on the market – Boehringer Ingelheim is looking to expand the uses of its rival Jardiance (empagliflozin), including in CKD where it has begun work on the EMPA-KIDNEY trial.
AZ is already in talks with regulators over results of DAPA-HF, and the FDA is due to make a decision on whether or not to approve a label expansion in the next six months after granting a fast priority review.
“We hope to bring those innovations to patients as soon as we can,” said Silon.
As well as Farxiga there are several others that are already approved and established in the company’s CVRM fold.
From the same deal with Bristol-Myers Squibb, AstraZeneca has the weekly GLP-1 class drug Bydureon (exenatide), giving it a presence in a market that is also hotly contested by Novo Nordisk and Eli Lilly.
Outside of diabetes is Brilinta/Brilique, a blood-thinning drug used for coronary artery syndromes and to reduce the rate of cardiovascular incidents in patients with coronary artery syndrome, or a history of heart attack.
And from a separate deal where it acquired ZS Pharma, AZ has Lokelma, approved for treatment of adults with excess potassium in the blood, or hyperkalaemia..
In the pipeline there are a host of other drugs in development, many of which originated from the biopharmaceutical firm MedImmune that AZ bought in 2007 for $15.2 billion.
Diseases targeted include non-alcoholic steatohepatitis, cardiovascular disease, hyperglyceridaemia, and diabetic kidney disease.
Silon is quick to point out that while these medicines are viewed separately by regulators, AZ’s mission is to look at these chronic diseases as a whole and try and meet the health needs of the world’s population, particularly in emerging markets.
Diabetes and other non-transmissible diseases are becoming problematic in these countries as people become richer and adopt Western lifestyles and AZ is hoping to address this with this range of different products.
Silon said: “These diseases are inter-related but are still distinct disease areas. The unmet need is huge. I think we need to continue to underline that cardiovascular, renal, and metabolic diseases are a driving force behind that.”
Richard Staines is senior reporter at pharmaphorum. He has been a journalist since the 1990s and has written for websites, newspapers and magazines. He has always had an interest in health and has been focusing on the pharma industry since 2010, interviewing industry leaders and covering stories on topics including regulation, mergers and acquisitions, and the latest clinical developments.