Boehringer, Lilly’s Jardiance ties to match AZ’s Farxiga with heart failure label

Boehringer and Eli Lilly have moved closer to a heart failure indication for their SGLT2 inhibitor Jardiance, as the FDA starts a fast-track review of the drug in its first use beyond diabetes.

The US regulator is looking at data from the EMPEROR-Reduced trial of Jardiance (empagliflozin), which found that the drug achieved a 25% reduction in the combined primary endpoint of cardiovascular death or hospitalisation compared to placebo.

Lilly and Boehringer claim almost 60% market share for Jardiance among SGLT2 drugs used to treat type 2 diabetes, driving blockbuster sales for the brand.

It was the top-selling drug in the SGLT2 inhibitor class in 2019, with sales of almost $3 billion, helped by side-effect problems that have afflicted first-to-market rival Invokana (canagliflozin) from Johnson & Johnson.

However its rivals – which also include AstraZeneca’s Farxiga (dapagliflozin)  – have moved more swiftly into areas like heart failure and chronic kidney disease (CKD) which have made large numbers of new patients eligible for treatment with the class.

The new FDA review – covering Jardiance as a treatment for adults with heart failure with reduced ejection fraction (HFrEF) in patients with and without diabetes – is Lilly and Boehringer’s first chance to fight back.

Farxiga won FDA approval for adults with HFrEF in May 2020, which helped to drive its third-quarter sales up by a third to $525 million. AZ picked up EU approval for the same indication the following November.

Lilly and Boehringer will be hoping for a swift FDA review so that Jardiance will not fall too far behind its competitor in the heart failure category, and that looks likely as the benefit in HFrEF increasingly appears to be an SGLT2 class effect.

GlobalData has said that heart failure could add billions to the sales of the two SGLT2 inhibitors, particularly if they also claim approvals in heart failure with preserved ejection fraction (HFpEF), a larger patient population.

It says Farxiga will reach peak sales of $9 billion in 2028, with Jardiance forecast to reach $4.6 billion, assuming a launch for HFrEF this year. The bulk of those sales will come from HFpEF, however,  as in this form of heart failure there is a huge unmet need and no approved therapies.

Boehringer and Lilly are waiting for the results of the EMPEROR-Preserved later in 2021, while AZ should also Farxiga in the DELIVER trial in HFpEF, with additional data on both HFrEF and HFpEF due from the DETERMINE study, before year-end.

Meanwhile, EMPEROR-Reduced also showed a slowdown in the rate of decline in kidney function among patients with HFrEF, an effect that Lilly and Boehringer are exploring in the CKD patient population in the EMPA-KIDNEY trial due to generate results in 2022.

Invokana was the first mover among the SGLT2 drugs in the kidney area, winning FDA approval towards the end of 2019 for diabetic kidney disease. After a couple of years of declining sales due to concern about a risk of lower limb amputation, Invokana managed a 25% gain to $224 million in third-quarter 2020.

Farxiga meanwhile has already been filed for CKD on the back of the DAPA-CKD trial, with a verdict due in the second quarter.

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NICE backs AZ’s Forxiga for heart failure

Just a few weeks after its EU approval for heart failure, AstraZeneca’s Forxiga has been backed by NICE for this use by the NHS in England and Wales.

Forxiga (dapagliflozin) – originally developed as a type 2 diabetes drug – is the first SGLT2 inhibitor to be approved for the treatment of symptomatic chronic heart failure with reduced ejection fraction (HFrEF) in adults with and without diabetes.

It got a green light for this use in the EU in early November and in the US in May, with the new indication helping to drive third-quarter sales up by a third to $525 million.

Approval for Farxiga was based on positive results from the phase 3 DAPA-HF trial, which showed Farxiga achieved a statistically significant and clinically meaningful 26% reduction of death or hospitalisation for heart failure compared with placebo.

Today, NICE issued draft guidance which recommends Forxiga as an option for treating symptomatic HFrEF in adults if used as an add-on to standard drugs, which would make around 260,000 additional people eligible for treatment with the drug.

Novartis’ Entresto (sacubitril/valsartan) is also used to treat HFrEF, an indication which propelled it to sales of almost $2 billion last year.

According to NICE, while there are no head-to-head trials comparing Entresto and Forxiga, AZ’s drug “is likely to be as effective as [Entresto] at reducing the risk of death from heart disease

AZ’s rivals Eli Lilly and Boehringer Ingelheim meanwhile are also attempting to develop their SGLT2 inhibitor Jardiance (empagliflozin) for heart failure. They suffered a setback a year ago when the drug failed to improve exercise ability in two phase 3 studies, but bounced back with the results of the EMPEROR-Reduced study in July.

GlobalData has said that heart failure could add billions to the sales of the two SGLT2 inhibitors, particularly if they also claim approvals in heart failure with preserved ejection fraction (HFpEF), a larger patient population. It says Farxiga will reach peak sales of $9 billion in 2028, with Jardiance forecast to reach $4.6 billion, assuming a launch for HFrEF in 2021.

AZ is also putting Forxiga through its paces in heart failure in combination with other drugs, including its mineralocorticoid receptor modulator AZD9977 and selective endothelin A antagonist zibotentan (also known as AZD4054), with mid-stage trials on the go.

Meanwhile, heart failure is just one area into which AZ is hoping to expand Forxiga before its patents start to expire in the coming years. It’s also looking at chronic kidney disease (CKD), and has picked up a breakthrough designation from the FDA for this indication.

Forxiga was the first medicine to significantly prolong survival in patients with CKD, either with or without diabetes, in the DAPA-CKD trial.

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Bayer data for kidney disease hope finerenone sets up filings

Bayer’s blockbuster ambitions for diabetic kidney disease (DKD) drug candidate finerenone look a lot firmer with the publication of data from the phase 3 FIDELIO-DKD trial.

Bayer teased the top-line result from the study back in July, providing the first clue that its sizeable investment in the finerenone programme could pay off, but kept the data under wraps other than to say the drug met the dual objectives of reducing renal and cardiovascular events in patients with type 2 diabetes and chronic kidney disease.

Now, the 5,734-patient study has been presented at the Kidney Week 2020 congress and simultaneously published in the New England Journal of Medicine, and the data look solid.

A second ongoing phase 3 trial – called FIGARO-DKD – is concentrating primarily on cardiovascular endpoints but also includes aptietnsd with earlier-stage kidney disease and has a read out due next year.

Bayer is eyeing regulatory filings before the end of 2020 on the back of the FIDELIO-DKD results, which would set up a clash with SGLT2 inhibitors, drugs for diabetes that are also emerging as promising therapies for DKD.

That includes Johnson & Johnson’s Invokana (canagliflozin) – already approved for diabetic kidney disease – as well as AstraZeneca’s Farxiga (dapagliflozin) which showed positive results in the DAPA-CKD trial in both diabetic and non-diabetic subjects just last week.

Finerenone – billed as a first-in-class non-steroidal, selective mineralocorticoid receptor (MR) antagonist – reduced the risk of kidney disease progression or renal death by 18% when added to the highest tolerated dose of standard therapy in FIDELIO-DKD.

The drug also cut cardiovascular outcomes – including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke or hospitalisation for heart failure – by 14%.

“Overactivation of the mineralocorticoid receptor contributes to inflammation and fibrosis in the kidneys and heart, which represents an unmet medical need,” said lead investigator Prof George Bakris of University of Chicago Medicine.

“The results with finerenone are highly relevant for these patients who currently have limited options,” he added.

There is also a huge number of them. Diabetes is the leading cause of kidney failure, and there are estimated to be almost 850 million people worldwide with chronic kidney disease (CKD).

If approved, finerenone would enter a market in which J&J is struggling to overturn the lingering impact of black-box warnings over amputation risks with Invokana that were dropped in the summer. The drugmaker sees kidney disease as its route to growth after a couple of years of declining sales, and is promoting the new use strongly.

AZ meanwhile is on a roll with Farxiga, with the new data in CKD building on recent data for the drug in heart failure that is helping to drive sales growth, although patent expirations and the threat of generic competition are looming.

Bayer is also eyeing a heart failure indication for finerenone, and now has a phase 3 trial in heart failure with preserved ejection fractions (HFpEF) in play that if successful would unlock a hitherto untapped market with no approved drugs.

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AstraZeneca Presents Results of Farxiga (dapagliflozin) in P-lll DAPA-CKD Study for Chronic Kidney Disease at ASN Kidney Week 2020

Shots:

  • The P-lll DAPA-CKD study involves the assessing of Farxiga (qd, 10 mg) + SOC vs PBO in 4304 patients with CKD stages 2-4 and elevated urinary albumin excretion, with/ out T2D
  • Results of subgroup analysis : RRR & ARR (5.8% & 37%) for patients whose CKD was primarily driven by diabetic kidney disease; (25% & 2.2%) for high B.P.; (57% & 7.5%) for glomerulonephritis; (42% & 5.0%) for CKD of other or unknown causes (ARR = 5.0%) respectively. Also showed reduction in in all-cause mortality as secondary outcome
  • Farxiga (PO, qd) is a first-in-class SGLT2 inhibitor indicated in adults for the treatment of insufficiently controlled T2D as both monotherapy & combination regimen as an adjunct to diet and exercise to improve glycemic control and has received FDA’s BTD & CHMP’s recommendation in Oct’2020

Click here ­to­ read full press release/ article | Ref: AstraZeneca | Image: NPR

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AstraZeneca’s Farxiga Receives the US FDA’s Breakthrough Therapy Designation for Chronic Kidney Disease

Shots:

  • The BT destination follows P-lll DAPA-CKD assessing Farxiga (10mg, qd) + SOC vs PBO in 4,304 patients with CKD Stages 2-4 and elevated urinary albumin excretion, with/ out T2D across 21 countries
  • Results: 39% reduction in the composite measure of worsening of renal function or risk of CV or renal death; 31% reduction in death from any cause
  • Farxiga (PO, qd) is an SGLT2 inhibitor indicated in adults for the treatment of insufficiently controlled T2D as both monothx. and combination therapy as an adjunct to diet and exercise to improve glycemic control, weight loss, and BP reduction

Click here ­to­ read full press release/ article | Ref: AstraZeneca | Image: DW

Related News: AstraZeneca Reports Results of Farxiga (dapagliflozin) in P-III DAPA-CKD Trial for Patients With and Without Type-2 Diabetes

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Study puts Jardiance in hot pursuit of AZ’s Farxiga in heart failure

The FDA’s approval of AstraZeneca’s SGLT2 inhibitor Farxiga in heart failure was a first for the class, but Boehringer Ingelheim and Eli Lilly are closing the gap with a positive pivotal trial for their rival drug Jardiance.

Top-line data from the phase 3 EMPEROR-Reduced study have shown that Jardiance (empagliflozin) beat out placebo on the primary objective of reducing death and hospitalisation rates in heart failure patients with and without diabetes.

The study was carried out in heart failure patients with reduced ejection fraction (HFrEF), the same group for which AZ claimed an FDA approval for Farxiga (dapagliflozin) in May.

Boehringer and Lilly now plan to present the data from EMPEROR-Reduced at the European Society of Cardiology (ESC) congress next month, and start filing for approval of Jardiance for HFrEF before the end of the year.

Jardiance was the top-selling drug in the SGLT2 inhibitor class with sales of almost $3 billion last year helped by side-effect problems that have afflicted Johnson & Johnson’s first-to-market Invokana (canagliflozin).

Farxiga has been gaining ground quickly however, with sales topping $1.5 billion in 2019 and growing another 20% in the first half of 2020, despite the impact of the coronavirus pandemic.

“The results of the EMPEROR-Reduced trial indicate that SGLT2 inhibitors have the potential to become a new standard of care for this disease, which will be a meaningful addition to currently established treatments,” said lead investigator Milton Packer of Baylor University Medical Center in Dallas.

Analysts at GlobalData have suggested that heart failure could add billions to the sales of the two SGLT2 inhibitors, particularly if they also claim approvals in heart failure with preserved ejection fraction (HFpEF), a larger patient population.

GlobalData has predicted that Farxiga will reach peak sales of $9 billion in 2028, while Jardiance is forecast to reach $4.6 billion, assuming a launch for HFrEF in 2021.

The bulk of those sales will come from HFpEF, which has “a huge unmet need and no specific standard of care,” it says.

AZ will however start losing patent protection for its drug in the coming years, depending on the outcome of patent litigation, so the launch of generics could rein in the SGLT2 market.

There have been numerous trial failures in HFpEF in recent years, including Novartis’ big selling heart failure therapy Entresto (sacubitril/valsartan), and Farxiga, Jardiance, and Merck & Co/Bayer’s vericiguat are the only drugs with positive data in this form of heart failure.

Boehringer and Lilly are waiting for the results of the EMPEROR-Preserved next year, while AZ is testing Farxiga in the DELIVER trial in HFpEF, with additional data on both HFrEF and HFpEF due from the DETERMINE study. Both of those Farxiga trials are also due to read out in 2021.

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AstraZeneca Report Results of Farxiga in P-III DAPA-CKD Study for Patients with Chronic Kidney Disease

Shots:

  • The P-III DAPA-CKD involve assessing of Farxiga ((dapagliflozin, 10mg, qd) + SOC vs PBO in 4,304 patients with CKD Stages 2–4 and elevated urinary albumin excretion, with and without T2D
  • The study met its 1EPs i.e. worsening of renal function or risk of death (defined as a composite of an eGFR decline ≥50%, the onset of ESKD and death from CV/ renal cause) and 2EPs i.e. time to first occurrence of the renal composite (sustained ≥50% eGFR decline, ESKD, and renal death
  • Farxiga (PO, qd) is an SGLT2 inhibitor indicated in adults for the treatment of insufficiently controlled T2D as both monothx. and combination therapy as an adjunct to diet and exercise to improve glycemic control, weight loss and BP reduction

Click here ­to­ read full press release/ article | Ref: AstraZeneca | Image: Bloomberg Quint




Trial shows AZ’s Farxiga slows onset of chronic kidney disease and cuts mortality

AstraZeneca’s Farxiga could be on course for another use, after trial results showed it slowed the worsening of renal function and cut the risk of death in patients with chronic kidney disease with and without type 2 diabetes.

Farxiga (dapagliflozin), an oral once-daily sodium-glucose co-transporter-2 (SGLT2) inhibitor, started life as a diabetes drug but AZ has begun trialling it in other cardiovascular and metabolic diseases.

It’s part of an ongoing trend started by Eli Lilly and Boehringer Ingelheim, who showed that their rival SGLT2 diabetes drug Jardiance (empagliflozin) cut the chances of cardiovascular events in high-risk patients with type 2 diabetes in 2016’s landmark EMPA-REG OUTCOMES trial.

Farxiga has already picked up indications to reduce risk of hospitalisation in heart failure patients with type 2 diabetes, and as a standalone treatment for heart failure in patients with reduced ejection fraction.

Last year, the FDA badged Farxiga as a Fast Track drug in chronic kidney disease, and also decided to offer the same level of regulatory support to Jardiance earlier this year.

The high level results from the phase 3 DAPA-CKD trial announced today show Farxiga produced a “statistically significant and clinically meaningful” effect when measured against a composite endpoint of worsening renal function or risk of death.

The endpoint was defined as a decline of at least 50% sustained decline in estimated glomerular filtration rate, onset of end stage kidney disease or cardiovascular renal death, in adult CKD patients with or without type 2 diabetes.

The trial also met all its secondary endpoints and AZ noted that Farxiga is therefore the first medicine to significantly reduce the risk of death from any cause in this patient population.

AZ added that the safety and tolerability profile for Farxiga was consistent with the well-established safety profile of the medicine.

The full DAPA-CKD trial results will be submitted for presentation at a forthcoming medical meeting.

Mene Pangalos, executive vice president of BioPharmaceuticals R&D, at AZ said that regulatory filings will follow.

He said: “DAPA-CKD is the first trial to demonstrate overwhelming efficacy, including improvement on survival, in chronic kidney disease patients both with and without type-2 diabetes.

“We look forward to sharing these exciting Farxiga results with the scientific community and health authorities worldwide.”

 

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