Novartis’ kidney transplant trial has crashed and burned. Having moved into phase 2 on the strength of evidence that iscalimab may prolong the durability of transplanted kidneys, Novartis stopped the study after an interim analysis found it may be worse than standard of care.
Investigators randomized 418 kidney transplant recipients to receive standard of care tacrolimus or one of three doses of iscalimab on top of other immunosuppressive therapies. The primary endpoint looked at the rate of death, graft loss and organ rejection over 12 months.
Novartis is yet to share data from the interim analysis but the headline finding is damning: iscalimab performed worse than tacrolimus. Faced with the failure, Novartis is stopping the kidney transplant study but pushing ahead with other trials of the drug candidate.
In recent years, Novartis has started a string of mid-phase studies of iscalimab in transplant patients, both liver and kidney, and people with diseases including systemic lupus erythematosus, Sjögren syndrome and type 1 diabetes. The activity is underpinned by evidence that inhibiting CD40 can act on various immune effector functions linked to transplant rejection and some autoimmune diseases.
Novartis laid out the case for using iscalimab in kidney transplant patients in 2019, when it showed that the organs of 60% of recipients of the drug had normal histology one year after transplant. None of the patients on tacrolimus had normal histology. That early promise failed to translate into improved outcomes in phase 2.
The failure dents the prospects of a drug with a long backstory. The asset originated from a 2004 deal between Chiron and Xoma. Novartis struck a deal to buy Chiron the next year and decided to take iscalimab forward as a treatment for B-cell mediated diseases. A phase 1 trial in rheumatoid arthritis patients got underway in 2014. That disease, and others, fell off Novartis’ hit list over the following years, but a multifront clinical campaign has continued.
Novartis saw the campaign leading to approvals in three indications in 2025 or later. With the kidney trial failing, liver transplant and Sjögren syndrome now carry Novartis’ hopes of getting the drug to market in the foreseeable future.