Earlier this month, AstraZeneca announced the success of its heart failure (HF) treatment Farxiga, branded as Forxiga in the EU. HF is a market in need of drug innovation and this success could pave the way for a new treatment strategy, helping to fulfil multiple unmet needs in this area.
New therapies which show greater mortality benefits than currently available products have the potential to take a large share of the HF market.
The Phase III DAPA-HF trial was the first to look at a sodium glucose co-transporter-2 inhibitor in patients with and without diabetes. Farxiga met its combined primary end points of reduction in cardiovascular (CV) death and reduced worsening of HF. It will be used as an adjunctive therapy to the standard-of-care products, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.
The trial itself ensured a balanced patient pool, as approximately 40% of the cohort had diabetes. This was a pivotal point within the trial, as Farxiga has proven its worth in diabetes by reducing CV risk factors. However, its benefit in HF patients without diabetes was unclear.
The DAPA-HF trial indicated that Farxiga shows great promise in all HF-reduced ejection fraction (HF-REF) patients regardless of diabetes comorbidity, thus increasing its target market. HF-REF is categorised as left ventricular ejection fraction (LVEF) of 40% or less, and all patients studied in the trial had an LVEF of ≤40%. Furthermore, the drug is also being studied in the DELIVER and DETERMINE trials in HF-preserved ejection fraction (HF-PEF), a condition with huge unmet need.
HF-PEF is characterised by LVEF of >49%, and the trials specify the inclusion criteria of patients with an LVEF of >40%. As the main contender in this treatment area, Novartis’ Entresto (sacubitril/valsartan) stumbled in its Phase III PARAGON-HF trial. This leaves the HF market wide open, and has provided AstraZeneca with the opportunity to be first to market for HF-PEF.
A burgeoning market
The success of the DAPA-HF trial could be the start of an increasing AstraZeneca market share in HF. Eli Lilly/Boehringer Ingelheim’s collaborative trial of empagliflozin for chronic HF is currently positioned as AstraZeneca’s lead rival in this space.
Empagliflozin has received fast track status by the FDA, and its Phase III EMPEROR-Preserved trial will look at HF symptoms and exercise capacity after treatment of the drug. Empagliflozin’s progress in HF follows the EMPA-REG OUTCOME trial, where it was shown to reduce risk of CV outcomes, including death.
Key opinion leaders (KOLs) interviewed by GlobalData have previously shared their thoughts on HF prescribing habits. They have noted that HF-PEF treatment options are so limited that they revolve around symptomatic management and treating comorbidities such as diabetes. Although there are more treatment options available for HF-REF, these focus on symptomatic management and reducing the risk factors of HF, such as diabetes. Therefore, Farxiga could be an ideal treatment option as it reduces CV outcomes while helping to treat the underlying risks in patients with diabetes. With further real-world evidence, and if Farxiga becomes a new prescribing practice in the large diabetic HF market, this familiarity may increase prescribing in the evidenced treatment of HF patients without diabetes.
The DAPA-HF trial details are to be presented at the European Society of Cardiology Conference 2019, where the next steps for the drug may also be discussed.