Ionis antithrombotic with reduced bleed risk clears phase 2b study

Patients with end-stage renal disease (ESRD) who are on dialysis often need to be treated with anticoagulants to prevent blood clots, but as a result, can experience bleeding side effects. Now, Ionis and Bayer think they have a new drug that could sidestep that risk.

In a phase 2b RE-THINC trial, their experimental antisense-based Factor XI inhibitor fesomersen was able to achieve a "substantial and statistically significant" reduction in levels of the clotting factor, indicating it was providing protection against clots.

A the same time, there was no increase in the incidence of major bleeding and clinically relevant non-major bleeding over the course of the 48-week study compared to placebo, said the partners.

ESRD tend to have underlying conditions like diabetes, high blood pressure, atrial fibrillation, and cardiovascular disease that increase their risk of blood clots, and systemic anticoagulants are routinely used as a preventative measure. However, the high rates of haemorrhage make the treatment challenging.

The results of RE-THINC will still need to be subjected to scrutinised at a future medial congress, but if fosemersen's potential in providing anticoagulation is borne out in further studies, it could mark a step-change in anti-thrombotic treatment of both chronic kidney disease (CKD) and cardiovascular disease.

Patients with CKD are known to have a higher risk of heart attacks and strokes, with the latter estimated to occur between five and 30 times more frequently, with the chances rising if they are on dialysis.

Fesomersen has arisen out of Ionis' LIgand-Conjugated Antisense (LICA) technology platform, which has attracted a string of pharma partners as well as underpinning the biotech's in-house programmes, in part because it produces stable oligonucleotides with a long duration of action.

The Factor XI-targeting drug only needs to be administered once per month, while most current anticoagulants – including Bayer's blockbuster Xarelto (rivaroxaban) – are dosed every day.

Bayer licensed fesomersen (formerly IONIS-FXI-LRx) from Ionis in 2015 with an upfront payment of $100 million and another $55 million promised should the drug advance beyond the phase 2 study in CKD.

In 2019, Ionis said it received a $75 million milestone payment from the drugmaker to generate a LICA version of the antisense drug and advance it into the phase 2b ESRD trial.

Bayer is also developing two other novel anticoagulants, namely oral Factor Xia inhibitor asundexian – recently fast-tracked by the FDA – and an antibody to Factor Xia called osocimab, which has also just completed a phase 2b study. Bayer hasn't yet revealed whether the results were positive.