Eledon Pharmaceuticals’ lead asset, tegoprubart, is going to late-stage trials in kidney transplant rejection prevention, despite missing its primary efficacy endpoint.
In the Phase II BESTOW trial (NCT06126380), tegoprubart failed to offer significant improvements to estimated glomerular filtration rates (eGFR) in patients who had received a kidney transplant when compared with a standard of care (SoC) immunosuppressant, tacrolimus.
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During the study, those dosed with the anti-CD40 ligand-binding antibody demonstrated an eGFR or 69mL/min/1.73m² after 12 months of treatment while patients on tacrolimus experienced a rate of 66mL/min/1.73m² at the same time period.
Despite its failure to meet the assigned efficacy endpoint, Eledon noted that, to its knowledge, tegoprubart’s impact on eGFR is the “highest to be reported to date” in a kidney transplant rejection prevention-focused clinical trial.
Tegoprubart’s impact on glomerular filtration was more pronounced in living-related donor recipient patients, with the rate sitting at 72mL/min/1.73m². High Kidney Donor Profile Index (KDPI > 35) transplant patients achieved 62mL/min/1.73m².
Meanwhile, the composite endpoint of efficacy failure recorded for tegoprubart was found to be non-inferior to tacrolimus, reaching 22% compared with 17% in the tacrolimus group. Efficacy failure comprises of death, graft loss and biopsy proven acute rejection.
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By GlobalDataAccording to the US-based biotech, if this result could be replicated in the upcoming Phase III study, it would be “sufficient to support tegoprubart’s approvability”. Efficacy failure is the approval endpoint currently employed by the US Food and Drug Administration (FDA) in this indication.
Tegoprubart’s safety edge
Tegoprubart’s safety profile could also bolster its chances of approval, as the drug triggered less metabolic, cardiovascular and neurological impacts than its SoC counterpart.
Throughout the BESTOW trial, one in 47 patients given tegoprubart experienced new-onset diabetes while this impact was seen in one sixth of patients receiving tacrolimus. It was a similar case for transplant-associated hypertension, which was seen in 15.9% of tegoprubart patients compared with the 25% observed in patients given tacrolimus.
Patients in the tegoprubart arm also required shorter dialysis, with the mean rate being 4.6 days compared with the 6.1 days seen in the tacrolimus group.
Though the drug’s safety profile is more favourable than tacrolimus, its need for intravenous (IV) administration may cut its potential market uptake, as tacrolimus offers an oral alternative that reduces the need for frequent trips to the clinic for infusions.
Fulfilling unmet needs for kidney transplant patients
While a range of therapies have recieved the regulatory green light in kidney transplant rejection prevention, the indication is still a significant area of unmet need.
Currently, between 10% and 15% of patients who receive a kidney transplant experience at least one acute rejection episode within the first year, which can lead to potential graft failure and reliance on dialysis.
The rate of rejections observed in patients, as well as the common adverse events (AEs) associated with tacrolimus, has prompted companies to explore more tolerable and efficacious alternatives.
Through these efforts, a number of drugs have reached the market. This includes Azurity Pharmaceuticals’ Myhibbin (mycophenolate mofetil oral suspension), as well as Sanofi’s Thymoglobulin (anti-thymocyte globulin, rabbit), which obtained approvals in 2024 and 2017, respectively.
However, there could soon be some new candidates on the market, as there are currently seven ongoing Phase III studies in kidney transplant rejection, according to GlobalData’s Intelligence Center.
This includes Hansa Biopharma’s Idefirix (imlifidase), which is currently being explored in two Phase III trials across Europe and North America.
The drug has already received conditional approval from the European Medicines Agency (EMA) and is forecasted to bring in $483m for Hansa in 2031, according to analysts at GlobalData.
Biogen’s felzartamab is also being put to the test in the Phase III TRANSCEND study, which will explore the drug’s efficacy in adult kidney transplant recipients with late antibody-mediated rejection (AMR).
GlobalData is the parent company of Clinical Trials Arena.
