Anthos doubles down on its novel blood thinner
The group continues its niche-targeting strategy with abelacimab’s latest pivotal trial.
The Novartis spin-off Anthos has long looked like the odd company out in the race to get a factor XI inhibitor, a novel class of anticoagulant, to market. The group, which is backed by the private equity firm Blackstone, is surrounded by big pharma hitters like Bayer, Bristol Myers Squibb and Johnson & Johnson.
Anthos is going after niches where it thinks it can play, and where it sees the greatest unmet need – as shown by a new phase 3 trial it started this month, evaluating its agent abelacimab in atrial fibrillation patients deemed unsuitable for current anticoagulants.
The uses Anthos is targeting could still be big business, its chief executive, John Glasspool, tells Evaluate Vantage. “All things are relative. I’d take a billion-dollar niche any day of the week.”
The group is also not discouraged by last year’s mid-stage failures of Bayer’s asundexian and Bristol/J&J’s milvexian. “I'm not disappointed by the data,” says Dan Bloomfield, Anthos’s chief medical officer. "I think the disappointment came from the way they set up their studies with the wrong endpoints and the wrong expectations.”
He says: “My interpretation is that the data support the class.” Bayer and Bristol/J&J clearly agree, having already pushed into phase 3.
Anthos believes that its project could have greater efficacy, being a dual factor XI and XIa inhibitor, while asundexian and milvexian only hit factor XIa. And abelacimab is a once-monthly subcutaneous injection, which could improve compliance over the daily oral agents.
Bayer recently pulled out of partnerships with Ionis and Aronora on their respective once-monthly subcutaneous assets, fesomersen and osocimab.
Underserved Afib market
All the groups are targeting atrial fibrillation patients at risk of stroke. Direct oral anticoagulants (DOACs) like Eliquis and Xarelto can be used in this group, but they come with a risk of bleeding. The hope is that factor XI inhibitors could lower this risk while providing similar or better efficacy.
Still, the companies are looking at distinct populations. Bayer and Bristol/J&J are studying their projects against DOACs, while Anthos plans to seek approval in patients who are not candidates for the established drugs, such as those on antiplatelet agents or with liver disease.
This untreated population accounts for around 40% of atrial fibrillation patients, Anthos estimates – comprising around 2.6 million patients in the US. In the just-begun 1,900-patient Lilac-Timi 76 trial the group hopes to see a 50% reduction in stroke rate with abelacimab versus placebo.
Regarding the choice of comparator, Mr Bloomfield does not see any ethical issues. “We’re asked how we can do a study with placebo in patients at risk for stroke. And the answer is, they’ve been on placebo for months.”
However, he concedes that this will be a “hard study to do”. So why is Anthos taking this path, rather than the one being trodden by its big pharma rivals? Mr Glasspool replies that showing efficacy in an untreated population will “enable access to patients much more easily than saying you’re replacing a DOAC”.
Another niche Anthos is going after is cancer-associated embolisms, where two phase 3 trials are well under way.
Here, DOACs are only recommended by guidelines, rather than being FDA approved, Mr Glasspool says – and the drugs are not used in those with gastrointestinal and genitourinary cancers, who are at increased risk of bleeding.
He reckons that in this indication abelacimab could ultimately pull in sales of $1bn. “In some indications that would commonly be considered a blockbuster; of course, within this area it might be considered a niche.”
The chief exec believes that Anthos could commercialise abelacimab itself for this use, but, with another 15 indications potentially in the works, he adds: “At some stage, to optimise this agent, it would be good to find at least a commercial co-promotion partner.”
First, though, Anthos will need to prove the factor XI doubters wrong.
|Ongoing studies of abelacimab|
|Azalea-Timi 71||Atrial fibrillation||Xarelto||Data expected 2024*|
|Lilac-Timi 76||Atrial fibrillation pts unsuited to current anticoagulants||Placebo||Started Jan 2023|
|Aster||Cancer-associated VTE||Eliquis||Completes Sep 2023|
|Magnolia||GI/GU cancer-associated VTE||Low molecular weight heparin||Completes Sep 2023|
|Note: all phase 3 trials except Azalea-Timi 71; *a previous Vantage article mistakenly stated that data were due Q1 2023. Source: Evaluate Pharma & clinicaltrials.gov.|