A win in a cardiovascular outcomes study is now pretty much a necessity for any diabetes or heart drug to avoid becoming an also-ran. But Vifor Pharma is hoping that three such trials will help broaden the use of its injectable iron therapy Ferinject to include heart failure patients with iron deficiency.
The product is currently approved for patients with iron deficiency anaemia, including those with chronic kidney disease – but there are signs that it could also improve heart failure outcomes. If Vifor can confirm this in larger studies sales could expand in an area where the company must believe there is underuse, and push Ferinject firmly into blockbuster territory.
Big in the US
EvaluatePharma sellside consensus already puts 2022 sales at just over $1bn. Over half of these revenues are forecast to come in the US, where Vifor is partnered with Daiichi Sankyo and the product is known as Injectafer.
Daiichi is carrying out the largest of the new studies, called Heart-FID, in 3,000 North American patients with stable heart failure with iron deficiency, who are receiving maximally-tolerated background therapy. Meanwhile, the Vifor-sponsored Affirm-AHF trial will focus on acute heart failure, while the Germany-based, investigator-led Fair-HF2 study is enrolling patients with systolic chronic heart failure.
Vifor appears to be covering all of its bases – Ferinject is already recommended in the 2016 European Society of Cardiology guidelines for symptomatic patients with systolic chronic heart failure and iron deficiency; meanwhile, a recent US guideline update included a new recommendation that intravenous iron replacement can improve exercise capacity and quality of life in heart failure patients with iron deficiency.
However, perhaps these recommendations have not been enough to accelerate sales as fast as Vifor and Daiichi would like, providing a motivation for the companies to go to the expense of carrying out large outcomes studies.
The Swiss company will hope the results from the latest trials will build on data from three smaller previous studies, Confirm-HF, Fair-HF and Effect-HF, all in chronic heart failure, which showed benefits on surrogate endpoints including the six-minute walk test.
|Heart failure trials of Ferinject|
|Study||N||Patient population||Primary endpoint(s)||Data||ID|
|Confirm-HF||304||Chronic HF||Change in 6-minute walk test at week 24||Reported||NCT01453608|
|Fair-HF||459||Chronic HF||Self-reported patient global assessment and NYHA functional status at week 24||Reported||NCT00520780|
|Effect-HF||174||Chronic HF||Change in Peak VO2 at week 24||Reported||NCT01394562|
|Affirm-AHF||1,100||Acute HF||HF hospitalisations and CV death after 52 weeks||H2 2019||NCT02937454|
|Fair-HF2||1,200||Chronic HF||HF hospitalisations and CV death after 52 weeks||H2 2020||NCT03036462; investigator-sponsored study|
|Heart-FID||3,000||HF||12-month death rate, hospitalisation rates, and 6-month change in 6-minute walk test||2021||NCT03037931; conducted by US partner Daiichi Sankyo|
However, regulators and payers will be more interested in harder endpoints like hospitalisation and death, and this is what the new outcomes trials will be looking at.
Ferinject has also shown promise here, with the Confirm-HF trial finding a 61% reduction in re-hospitalisations, although this was not its primary endpoint. In addition, a meta-analysis of four trials – Confirm-HF, Fair-HF, Efficacy-HF and FER-CARS-01 – showed that Ferinject reduced recurrent heart failure hospitalisations and cardiovascular death by 47%.
This appears to compare favourably with the 20% reduction in heart failure hospitalisations and cardiovascular deaths seen in the Paradigm-HF trial of Novartis’s heart failure drug Entresto, Stifel analysts noted today. However, Paradigm-HF was much bigger, enrolling nearly 8,500 patients, and was not limited to iron-deficient patients. Entresto is forecast to sell $4bn by 2022.
Even so, the niche Ferinject will be targeting – if successful – should be a sizeable one: iron deficiency is present in around half of heart failure patients, according to the authors of the aforementioned meta-analysis.
But outcomes studies are unpredictable, not to mention time-consuming and expensive. It is probably a risk Vifor has to take if it wants to inject new life into Ferinject – but it is a gamble nonetheless.