Calliditas plans to file rare kidney disease drug Nefecon after phase 3 success

Swedish biotech Calliditas has announced plans to file its rare disease drug Nefecon with the FDA early next year following positive results from a phase 3 clinical trial.

The company has been developing Nefecon to treat the primary IgA nephropathy, a rare disease that affects the kidney but is caused by overproduction of antibodies produced in the lining of the small intestine, for which there are no approved medications.

Approval by the FDA would give Calliditas a clear shot at the market for the disease affecting 130,000-150,000 people in the US, although US biotech Aravive has a potential competitor in mid-stage clinical development.

Calliditas said part A of the global phase 3 NeflgArd clinical trial has met its target, measuring the effect of Nefecon versus placebo in patients with the disease known as IgAN for short.

Nefecon is a formulation of the established immunology drug budesonide, which targets the Peyer’s patches that are over-active in patients with IgAN.

The antibodies produced as a result lodge in the kidneys, causing severe complications.

The trial met its primary objective of demonstrating a statistically significant reduction in urine protein creatinine ratio (UPCR) or proteinuria after nine 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% mean reduction in the 16 mg arm versus baseline, with placebo showing a 5% mean reduction versus baseline, resulting in a 27% mean reduction at 9 months of the 16 mg arm versus placebo.

The 199-patient 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 with placebo.

The eGFR endpoint showed a treatment benefit of 7% versus placebo at nine months, reflecting stabilisation in the treatment arm and a 7% decline of eGFR in the placebo arm.

Collectively the efficacy data from nine months treatment with 16 mg of Nefecon indicated a significant and beneficial effect on key factors correlated to the progression to end stage renal disease (ESRD) for IgAN patients, the company said.

The results indicate that Nefecon was generally well-tolerated and were consistent with the known safety profile of Budesonide. The number of withdrawals in the trial was significantly less than what was seen in the Phase 2b NEFIGAN trial.

Calliditas plans to file for an accelerated approval based on these early results with the FDA in the first quarter of 2021.

A filing for a conditional approval with the European Medicines Agency will follow in the second half of next year.

If approved, Calliditas aims to market Nefecon for IgAN by itself in the US and through collaborations in other regions.

Both of these approvals will require confirmatory data from a larger set of patients for the drug to remain on the market permanently.

Calliditas is led by CEO Renee Aguiar-Lucander and has funded development of Nefecon following an $81m IPO in 2018.

Aguiar-Lucander said in a statement: "Calliditas has been a pioneer in IgAN for many years and we are excited to be the only company to have reported out a positive phase 3 trial in this indication. This result brings hope to thousands of patients who today have no approved treatment alternatives."