SYNOPSIS:
- GlaxoSmithKline Plc released positive trial results for a potential blockbuster anemia pill the company is hoping will bolster its pharma portfolio as the drugmaker prepares to spin off its consumer healthcare business next year.
- The data make Glaxo a contender for one of the first anemia treatments in pill form for both dialysis and non-dialysis patients in the U.S. and Europe.
- Daprodustat could be one of the first oral treatments in the U.S.
- In August, the Cardiovascular and Renal Drugs Advisory Committee (CRDAC) of the U.S. Food and Drug Administration (FDA) denied AstraZeneca and FibroGen‘s drug Roxadustat for the treatment of anemia in patients with chronic kidney disease (CKD).
GlaxoSmithKline’s Novel Anemia (Daprodustat) has Notched up A First-In-Class Success While AstraZeneca-FibroGen’s Akebia Failed.
The third-in-line GlaxoSmithKline has notched up a first-in-class success. After the FDA’s resounding rejection for AstraZeneca and FibroGen’s Roxadustat.
For both dialysis-dependent and nondialysis patients with anemia from chronic kidney disease, GSK’s Daprodustat matched up to traditional erythropoiesis-stimulating agents (ESAs) in terms of heart safety, as measured by a composite marker of time to first major adverse cardiovascular event (MACE). The detailed data from two phase 3 trials, ASCEND-D and ASCEND-ND, were unveiled at American Society of Nephrology Kidney Week 2021.
Armed with the two trial wins, GSK plans to file Daprodustat with the FDA in the first half of 2022, teeing up what could be the company’s first new drug launch after its planned consumer health spinoff. GSK has recently pegged the drug’s peak sales potential at between 500 million pounds and 1 billion pounds. GSK partner Kyowa Kirin has been selling the drug in Japan since last year under the brand name Duvroq.
Beyond MACE, an important safety problem the FDA has flagged for roxa is an increased rate of blood clots. For both trials, GSK set a secondary endpoint aiming to show that Daprodustat works better than ESA on the composite marker of MACE plus blood clots. However, neither trial was able to show superiority on that marker for the GSK drug.
In dialysis patients, the ASCEND-D trial showed a trend favoring Daprodustat, but it just missed statistical significance on the MACE plus blood clots marker, Ajay Singh, M.D., of Harvard Medical School, principal investigator of the ASCEND program, said in an interview. The positive trend was driven by a lower number of vascular thrombosis events for dapro, he added.
The ASCEND-ND trial in nondiaysis patients didn’t follow that same favorable trend for Daprodustat . The difference in thrombosis benefit may be the result of different trial population, Singh said, as vascular thrombosis may not occur as much in the nondialysis population.
Before concluding Daprodustat is heart-problem-free at least when compared to ESAs, industry watchers have another data set to consider. In a third phase 3 trial dubbed ASCEND-ID in incident dialysis patients, a numerically higher rate of worsening high blood pressure cropped up in the Daprodustat arm when compared with Aranesp, despite the Daprodustat group being younger and having less history of heart failure. The rates were 24% for Daprodustat and 19% for Aranesp.
The ASCEND-ID trial wasn’t powered to conclusively measure cardiovascular differences, Singh noted. The blood pressure difference deserves further investigation, but Singh said he’s not concerned about the signal.
“If you look at the broader population of stable dialysis patients in the [ASCEND-D] study and you look at hypertension as an adverse event of special interest, there was no trend that was unfavorable to Daprodustat ,” he said.
in all, Daprodustat essentially showed itself as a drug with a similar efficacy and safety profile as conventional ESAs. But the oral drug still deserves a place on the market with injectable agents, Singh said.
As it stands, the nondialysis population of anemia is relatively under-treated because some patients don’t have easy access to healthcare facilities and anemia treatment currently is a physician-supervised process, Singh noted. Plus, patients don’t like getting injections because they’re uncomfortable.
“If you can get an oral drug that they can take, you’re going to increase the proportion of people who should be treated to get treatment,” Singh said.
Glaxo Unveils Positive Data for Potential Blockbuster Anemia Drug:
GlaxoSmithKline Plc released positive trial results for a potential blockbuster anemia pill the company is hoping will bolster its pharma portfolio as the drugmaker prepares to spin off its consumer healthcare business next year.
Results from five studies found the oral treatment for patients with anemia due to chronic kidney disease either maintained or improved hemoglobin levels compared with current medication, without increasing the cardiovascular risk, according to data presented Friday.
The data make Glaxo a contender for one of the first anemia treatments in pill form for both dialysis and non-dialysis patients in the U.S. and Europe. The company had been lagging behind two other similar treatments from AstraZeneca Plc and its partner FibroGen Inc., and Akebia Therapeutics Inc. and partner Otsuka Pharmaceutical Co., but both have suffered setbacks over the last 18 months.
More than 700 million people globally suffer from chronic kidney disease, with one in seven estimated to develop anemia. Patients must currently undergo injections to manage the condition. Glaxo is hoping its oral drug – Daprodustat – will be among a new line-up of key money-makers for its revamped pharma and vaccines company after it separates from its consumer arm in mid-2022.
In June, the company told investors it was forecasting annual sales of between 500 million pounds ($673 million) and 1 billion pounds. Glaxo first released high-level positive results from the trials in July.
There’s an opportunity “with an oral drug for the patients to, in some aspects, take a little bit more control of their disease because they’re no longer reliant at least for the anemia to have to go in to see the healthcare provider for an injection,” Chris Corsico, Glao’s head of development, said in an interview.
The data published Friday crucially shows the drug has no increased heart risk for dialysis or non-dialysis patients compared to an erythropoietin stimulating agent — an injection that is the current standard of care. This has been one of the issues hampering other drugmakers, giving rise to concerns cardiovascular side effects could be a class-wide issue for the drug type.
The treatments from Glaxo and its rivals have already been approved in Japan, where regulators don’t require data on the cardiovascular impact, as well as some other markets. None has yet secured authorization in the U.S. or Europe. Akebia has applied for approval from the U.S. Food and Drug Administration and a decision is expected by the end of March. Glaxo is planning to submit its results to regulators globally in coming months.
The FDA recently rejected AstraZeneca and FibroGen’s roxadustat for the treatment of anemia in patients with chronic kidney disease.
The logic behind the panel’s decision:
It’s worth discussing what led to this decisive rejection. While FDA staffer Dr. Saleh Ayache noted that “the FDA believes the Applicant has provided substantial evidence of efficacy,” CRDAC chair Dr. Julia Lewis indicated that “there are concerns over adverse safety.”
To this point, FibroGen announced in April that the disclosed safety analyses for roxadustat from November 2019 in the treatment of anemia of CKD were incorrect.
In the original presentation of the study’s data, the risk of non-dialysis-dependent (NDD) patients taking Roxadustat and experiencing major adverse cardiac events (MACE) over the duration of the Phase 3 trial was 8% higher than for patients taking placebo. The revised data showed a slight increase in that risk, to 10% more than placebo, adding to the overall risk profile of the drug and working against the odds of a potential FDA approval.
The risk of dialysis-dependent (DD) patients taking Roxadustat and suffering from MACE was initially thought to be 4% lower than for those taking peer drug epoetin-alfa (Epogen, developed by Amgen and Johnson and Johnson). However, the revised data showed that the probability of DD patients taking Roxadustat and enduring MACE was actually 2% higher than Epogen. This meant that AstraZeneca and FibroGen were no longer able to claim that Roxadustat was safer than Epogen in DD patients, which was a claim that previously gave Roxadustat an advantage over Epogen.
The risk of incident dialysis (ID) patients who have been on dialysis for four months or less taking Roxadustat and experiencing MACE was initially thought to be 30% lower compared to Epogen, but the corrected data showed that the risk of MACE complications was only reduced by 18%. While Roxadustat remains safer than Epogen in ID patients, the advantage is far less than what was thought to be the case initially.
AstraZeneca and FibroGen will now consider funding an additional clinical trial to continue pursuing FDA approval for roxadustat to treat CKD-related anemia. The trial would test whether a lower dosage of roxadustat would improve its safety profile, possibly allowing FDA approval later down the road assuming efficacy remained steady.
About GSK:
GlaxoSmithKline plc (GSK) is a British multinational pharmaceutical company headquartered in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham, GSK was the world’s sixth largest pharmaceutical company according to Forbes as of 2019, after Pfizer, Novartis, Roche, Sanofi, and Merck & Co. GSK is the tenth largest pharmaceutical company and #296 on the 2019 Fortune 500, ranked behind other pharmaceutical companies including China Resources, Johnson & Johnson, Roche, Sinopharm, Pfizer, Novartis, Bayer, Merck, and Sanofi.
The company has a primary listing on the London Stock Exchange and is a constituent of the FTSE 100 Index. As of August 2016, it had a market capitalisation of £81 billion (about US$107 billion), the fourth largest on the London Stock Exchange. It has a secondary listing on the New York Stock Exchange.
The company developed the first malaria vaccine, RTS,S, which it said in 2014 it would make available for five percent above cost. Legacy products developed at GSK include several listed in the World Health Organization’s List of Essential Medicines, such as amoxicillin, mercaptopurine, pyrimethamine, and zidovudine.
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