With an Aug. 22 PDUFA date set, Tricida Inc. said it received an FDA notification regarding the NDA for veverimer (TRC-101) for treating metabolic acidosis in chronic kidney disease (CKD) patients, noting that it had identified deficiencies precluding discussion of labeling and postmarketing requirements/commitments.

The company said the notification provides no specifics about the deficiencies. The FDA stated that “the notification does not reflect a final decision on the information under review,” according to the company. Tricida said it will sit down with the FDA to get a better understanding of the deficiencies so they can be resolved. In the meantime, the company said it can’t evaluate how addressable the FDA concerns may be.

Cowen analyst Phil Nadeau wrote Thursday that the notification suggested veverimer’s first cycle approval is now unlikely and the company is likely to receive a complete response letter on the August PDUFA since there is no mechanism to set up a meeting with the FDA before the date. Nadeau speculated that the FDA may want more data supporting serum bicarbonate use as an endpoint reasonably likely to predict a clinical benefit.

Veverimer is a non-absorbed orally administered polymer.

It is believed that metabolic acidosis, a condition that occurs when the kidney cannot excrete enough acid or balance its acid production, accelerates deterioration of the kidney, increasing the risk of muscle wasting and causing bone density loss. The condition may affect as many as 3 million patients in the U.S. alone. There are no FDA-approved chronic therapies for treating it.

The South San Francisco-based company’s stock (NASDAQ:TCDA) took the news badly, with shares closing 40.3% lower July 16 at $15.64.

Tricida has its confirmatory postmarketing trial of veverimer, VALOR-CKD, underway and doesn’t plan to modify or suspend it. Interim data from the trial are expected in 2022 or 2023 and the final data aren’t expected until 2024 or 2025.

The FDA accepted veverimer’s NDA for its accelerated approval program in November 2019 based on strong phase III extension data released in March 2019. The 40-week extension trial, TRCA-301E, in 196 patients hit all its primary and secondary endpoints.

The extension trial followed the 12-week TRCA-301 study of 217 randomized patients with non-dialysis-dependent CKD and metabolic acidosis. Of 208 patients completing the trial, 196 opted to continue with the extension. They were assigned to the same blinded treatment received in the parent trial, with 114 receiving TRC-101 and 82 receiving placebo, of which 111 and 74, respectively, completed one year of treatment.

The endpoint of TRCA-301E – assessment of the long-term safety profile – showed fewer TRC-101 patients (2.6%) discontinued treatment early when compared with placebo patients (9.8%). Serious adverse events occurred in 1.8% of treated patients and 4.9% of placebo patients, and gastrointestinal adverse events occurred in 21.4% of TRC-101 patients and 25.9% of placebo patients. All four secondary endpoints achieved high statistical significance in assessing the durability of effect of TRC-101, both on blood bicarbonate levels and on measures of physical function.

In May, Tricida closed an offering of $200 million aggregate principal amount of its 3.5% convertible senior notes due 2027 in a private offering to institutional buyers. Tricida estimated net proceeds will be about $193 million. Tricida said the money would be spent as working capital and for general corporate purposes.

Chronic kidney disease treatments brought in $12.9 billion dollars in the U.S., western Europe and Japan in 2015 and that market is expected to grow to $21.9 billion by 2025, according to DRG.

No Comments