Tricida’s bid for speedy approval of a drug for a condition caused by chronic kidney disease has been rejected by the FDA, which is asking for data that may require conducting another clinical trial.
The South San Francisco-based biotech had tested its drug, veverimer, in a Phase 3 study and a follow-on extension study, both of which were part of the application submitted for regulatory review. According to Tricida (NASDAQ: TCDA), the FDA now wants more information about the magnitude and durability of the drug’s effect.
The agency signaled its concerns to Tricida in July, when it sent the company a letter stating it has “identified deficiencies that preclude discussion of labeling and postmarketing requirements/commitments at this time.” In a regulatory filing, Tricida said that the FDA’s notification did not specify the deficiencies.
Veverimer is an experimental treatment for metabolic acidosis, a chemical imbalance that leads to the body becoming more acidic. Tricida estimates that 3 million patients in the US have metabolic acidosis and chronic kidney disease in stages 3 to 5 that does not require dialysis.
Metabolic acidosis is believed to speed up kidney deterioration, as well as bone loss and muscle wasting. It can be addressed with intravenous or oral doses of sodium bicarbonate, a base that neutralizes the acid. But Tricida notes that most patients with chronic kidney disease also have hypertension, cardiovascular disease, or heart failure—conditions that require patients to stick to a low-salt diet.
Tricida wants to offer a sodium bicarbonate alternative. The company’s polymer drug isn’t absorbed by the body. It’s designed to bind to acid in the gastrointestinal tract, and then remove it as it’s carried away in bodily waste. Reducing acid levels in this manner is intended to increase bicarbonate levels in the blood without the addition of sodium. The company says this approach would give sodium-sensitive patients a chronic treatment option for metabolic acidosis.
Showing an increase in biocarbonate in the blood was the pivotal study’s surrogate endpoint, a clinical trial goal that’s short of a direct measure that a therapy is addressing a disease but still indicative that it works. According to Phase 3 results published last year in The Lancet, 59 percent of patients (71 of 120) met that goal compared to 22 percent of those (20 of 89) given a placebo. The most common adverse events reported included diarrhea, flatulence, nausea, and constipation.
According to The Lancet paper, although veverimer effectively and safely corrected metabolic acidosis, longer-term studies are needed to assess the drug’s effect on a patient’s physical function. Those studies can also assess the impact of metabolic acidosis, including the progression of chronic kidney disease and bone problems. Tricida says the FDA letter asks for more data about the drug’s effect based on the surrogate endpoint. The company adds that the agency “expressed concern as to whether the demonstrated effect size would be reasonably likely to predict clinical benefit.”
The rejection letter noted no safety concerns associated with veverimer and the FDA said there were are multiple options for addressing the regulator’s concerns, according to Tricida. Those options include another clinical trial, which may still fall under the regulator’s accelerated approval program. The program grants a speedier review and approval for drugs that address an unmet medical need. That review can be done according to surrogate endpoints, but a company will then be required to conduct an additional postmarketing clinical study to confirm the drug’s benefit.
Drug developers seeking accelerated approval typically have their postmarketing studies underway even as their experimental therapies are still under review, and that’s the case with Tricida. The Tricida study is comparing the outcomes of patients treated with veverimer against those who were given a placebo. Earlier this month, in its report of financial results for the second quarter of this year, Tricida said that it expects to complete enrollment in the confirmatory study in the first half of 2021.
Tricida says it plans to request meeting with the FDA in coming weeks, which it expects could occur early in the fourth quarter of this year. After that meeting, Tricida says it will provide an update on the company’s next steps with its lead drug candidate. According to the company’s second quarter financial report, Tricida had about $437 million in cash, cash equivalents, and short and long-term investments. The company believes it has enough money to fund operations into early 2022.
|Want more Xconomy content? Subscribe today for free newsletters, event and webinar alerts, whitepapers, podcasts, and more.|