Evoke Pharma’s (NASDAQ:EVOK) discovery that its metoclopramide nasal spray, known as Gimoti, to treat symptoms of gastroparesis, a delayed emptying of stomach contents, reduced symptoms in women, but not in men, and that metoclopramide has significantly different exposure in men, compared with women, led the company to file a female-only NDA with the FDA in June.
Last week, the FDA accepted the NDA for review and set a PDUFA date of April 1, 2019 for a decision on the application.
“Unlike Reglan, the approved oral medication for gastroparesis, nasal delivery of Gimoti has been shown to bypass the gastrointestinal tract and directly enters the bloodstream,” David Gonyer, president and CEO, says in an interview with BioTuesdays.
Mr. Gonyer explains that Gimoti is similar to the approved oral formulation of metoclopramide but with a new mode of delivery. “Nasal delivery of metoclopramide has the potential for predictable absorption regardless of gastric emptying delays and symptom relief even during flares,” he adds, noting that absorption via a nasal spray would not be affected by patient nausea and vomiting.
In December 2016, the FDA agreed that a pharmacokinetic (PK) trial of Gimoti could serve as the basis for a 505(b)(2) NDA submission, along with efficacy and safety data from earlier clinical trials. Gimoti met comparative bioavailability criteria in a PK study, compared with Reglan, the reference listed drug.
“As we analyzed the PK data, we found significantly lower levels of the drug in men, compared with women, that could not be explained by body mass or weight, regardless of the route of administration of the drug,” he recalls. The company has filed new patent applications related to the discovery.
Mr. Gonyer points out that differences in metoclopramide PK measurements between women and men, regardless of the route of administration, were also found in a retrospective analysis of data from an earlier PK study conducted by the company.
Evoke’s female-only NDA for the treatment of gastroparesis is based on a dose in women equivalent to Reglan tablets. The filing also included supporting efficacy and safety data from earlier Phase 2b and Phase 3 trials, specifically for women, as well as plans for a post-approval safety study. Evoke is hoping for FDA approval of Gimoti during the first half of 2019.
FDA Meetings: Pathway to an NDA
There are some 12 million to 16 million patients with symptoms of gastroparesis in the U.S., of which 80% are women, with only one FDA-approved drug. However, delayed emptying of the contents in the stomach into the small intestine, in the absence of an obstruction, interferers with the oral drug’s absorption.
“This is clearly an unmet clinical need,” Mr. Gonyer contends, noting that the prevalence of the disorder is rising because of the growing number of patients with diabetes, a leading cause of gastroparesis.
He suggests that only an estimated two million to three million patients are now receiving treatment for gastroparesis, resulting in some four million prescriptions of oral metoclopramide written annually. “This is the market we would go after initially,” he suggests, adding that the estimated prescription market for gastroparesis could reach $4-billion.
Symptoms of the disorder include nausea, abdominal pain, early satiety, bloating, prolonged fullness and vomiting, which can further complicate with the effectiveness of Reglan tablets.
The impact on patients includes diminished quality of life, malnourishment, poor diabetes control and hospitalizations that can average six days at costs of $3.5-billion in 2004, the latest year for which figures are available, Mr. Gonyer points out.
Evoke has patent protection for a nasal administration of metoclopramide to treat symptoms associated with gastroparesis and nasal formulations of metoclopramide, and has filed patents to cover gender differences of gastroparesis that would expire in 2032.
Mr. Gonyer points out that Evoke currently is putting the initial steps in place to commercialize Gimoti. “We have developed considerable chemistry, manufacturing and controls data, three years of product stability and a commercial agreement with a contract manufacturer.”
In addition, he says the company has an ongoing relationship with Syneos Health to arrange a commercial infrastructure for sales and marketing.
There are about 7,200 metoclopramide prescribing gastroenterologists in the U.S., which would require a small sales force of 50-to-100 people, he suggests. “Market research shows that physicians understand that a nasal delivery may improve absorption and provide faster absorption of metoclopramide, compared with the oral product, and may allow patients with vomiting to absorb the medication.”
According to Mr. Gonyer, Gimoti should be widely available to members of commercial insurance plans, with Tier 3 “unrestricted” or “restricted” coverage, which is typical for branded products. In addition, reimbursement would likely take into account a lack of competitive products, a large unmet medical need and a potential reduction in hospitalization costs, he adds.
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