FDA Extends Action Date for Calliditas Nefecon

The U.S. Food and Drug Administration has extended the PDUFA goal date for Calliditas Therapeutics’ New Drug Application seeking accelerated approval for Nefecon in IgA by three months to December 15, 2021.

Photo: Renée Aguiar-Lucander, CEO at Calliditas

In March 2021 Calliditas filed for FDA approval using the Accelerated Approval Program, based on the proteinuria endpoint as previously discussed with the Agency, reflecting data from the 200 patients in Part A of the NefIgArd trial.

In its review of the company’s application for approval, the FDA has requested further analyses of the NeflgArd trial data which the company has provided. The Agency has classified these analyses as a major amendment to the NDA. The amendment mainly provides additional eGFR and other related analyses as further support of the proteinuria data provided in the NDA submission. The FDA has therefore extended the PDUFA goal date to December 15, 2021.

IgA nephropathy (IgAN) is a rare chronic kidney disorder in which an estimated 20 to 40 percent of patients progress to end-stage renal disease within 10 to 20 years of diagnosis. IgAN is often defined by progressive increases of blood and protein in the urine and acute onset of nephrotic syndrome. The disorder is estimated to affect more than 100,000 people in the U.S. and is one of the leading causes of acute nephritis in Europe and Japan.

Nefecon is a patented oral formulation of a potent and well-known active substance – budesonide – for targeted release. The formulation is designed to deliver the drug to the Peyer’s patch region of the lower small intestine, where the disease originates, as per the predominant pathogenesis models. Nefecon is derived from technology that allows for the substance to pass through the stomach and intestine without being absorbed, and to be released in a pulse like fashion only when it reaches the lower small intestine.

The global phase 3 clinical trial NefIgArd, which investigated the effect of Nefecon versus placebo in patients with primary IgA nephropathy (IgAN), consists of two parts. Part A, which was designed to provide the basis for regulatory submissions and approvals, evaluates data on the efficacy and safety of Nefecon.

The trial met its primary objective of demonstrating a statistically significant reduction in urine protein creatinine ratio, UPCR or proteinuria, after 9 months of treatment with 16 mg of Nefecon compared to placebo, with significant continued improvement at 12 months. The primary endpoint analysis showed a 31 percent mean reduction in the 16 mg arm versus baseline, with placebo showing a 5 percent mean reduction versus baseline, resulting in a 27 percent mean reduction at 9 months of the 16 mg arm versus placebo. The trial also met the key secondary endpoint, showing a statistically significant difference in estimated glomerular filtration rate or eGFR after 9 months of treatment with Nefecon compared to placebo. The key secondary endpoint, eGFR, showed a treatment benefit of 7 percent versus placebo at 9 months, reflecting stabilization in the treatment arm and a 7 percent decline of eGFR in the placebo arm.

Part B of the NefIgArd study is designed to be a confirmatory post-market observational trial to confirm long-term renal protection and assess the difference in kidney function between treated and placebo patients as measured by eGFR over a two-year period from the start of dosing of each patient. The 360-patient population of the complete phase 3 trial includes another 160 patients enrolled in addition to the 200 patients from Part A. The trial was fully recruited in January 2021, and aims to read out data in early 2023, after all patients have completed 2 years in the trial.

“Our NDA for Nefecon is the first time that the FDA is considering an approval on the basis of proteinuria as a surrogate endpoint for accelerated approval in IgA nephropathy, requiring an in-depth review process,” said Renée Aguiar-Lucander, CEO at Calliditas. “We will continue to cooperate closely with the FDA as they complete the review of our NDA.”