More positive PhIII data set stage for Scynexis' vaginal yeast infection drug approval
Months after unveiling data that showed its lead experimental compound, ibrexafungerp, helped patients with vaginal yeast infections, antifungal drug developer Scynexis is one step closer to the finish line with a second positive pivotal trial.
The company — which burst into the zeitgeist as one of the few companies testing a Candida auris therapy (the same drug ibrexafungerp) in human trials — is gearing up to submit a marketing application in the second half of this year, for what it claims is the first and only oral, non-azole treatment for vaginal yeast infections, a condition that affects three out of four women across their lifetimes but has limited treatment options.
Scynexis chief Marco Taglietti said in an interview he does not foresee any issue in filing the marketing application, and since the approval is expected to come by mid-2021, the FDA will likely be working normally.
Given the majority of women who get these infections are in the childbearing age of between 20 to 40, a virtual launch is something the company has in any case been thinking about, he added.
It has been decades since a fresh family of antifungals has come on to the market — at the moment there are three classes of antifungals in clinical use, including azoles and echinocandins. The most popular antifungals in use today were introduced in the 1980s and this class is increasingly losing its potency, as fungal pathogens mutate.
Ibrexafungerp belongs to a new class of antifungals called glucan synthase inhibitors, and has shown to be effective against a broad range of fungal infections, including resistant strains, according to Taglietti.
In the United States, there is one oral antifungal, fluconazole, which has been used for over two decades for fungal infections like vaginal yeast infections and the copay for patients is typically in the range of $15 to $20, Taglietti said.
Since Scynexis’ treatment (if approved) would be treating patients who do not respond to fluconazole, the drug will be priced at a premium — a list price of $300 to $400, which would work out to a copay of $25, to $30, he added.
The latest trial data emanate from the 366-patient VANISH-306 study, which tested the drug against a placebo. Patients enrolled had experienced an acute episode of vulvovaginal candidiasis (VVC), with signs and symptoms score of four or greater on a scale of zero to 18.
The drug induced a ‘clinical cure’ (defined as complete resolution — or score of 0 — at the test-of-cure visit on day 10) rate of 63.3 %, marking a statistically significant performance over the placebo arm, Scynexis said.
The secondary endpoint of mycological eradication was also met. Placebo data were not disclosed. On the safety side, severe adverse events were rare, and no severe side-effects were attributed to the drug.
The data reinforced the results of the VANISH-303 trial, which readout in November.
The drug is also being evaluated for use in the CANDLE study in patients with recurrent VVC — the results are expected in 2021. This study, since it concerns patients who do not have any treatment options, is expected to continue enrolling as planned and be completed by the end of the year, Taglietti said.
There are roughly 14 million VVC cases treated with oral fluconazole annually in the US and at least 15% of patients experience treatment failure, Needham analyst Alan Carr wrote in a note.
“A 25% peak penetration of the 15% failure subgroup in 2030 generates sales of around $450M ($500 net rev/ course w/ 5% annual price increases; approximately 585,000 patients on ibrexafungerp in 2030)”
Meanwhile, rival drug developer Mycovia is conducting a pair of late-stage trials testing its long-acting azole VT-1161 in recurrent VCC patients — data from both studies are expected in the second half of 2020.
Trials testing the ibrexafungerp’s use in invasive aspergillosis and refractory invasive fungal infections are also continuing undisturbed, Taglietti said. “These are hospitalized patients with severe infections, invasive infections, that are life-threatening. Therefore Covid-19 or no Covid-19 — these patients, they need something.”
At Scynexis, the biggest change since the explosion of Covid-19 has been that the majority of the company’s workforce has been working from home, although employees did have the option to work from home for 2-3 days a week previously.
“I can tell you that I don’t like to work remotely … there is no separation between work and private life, there is no difference between the weekend and work weeks, and everything becomes Groundhog Day. And honestly, the refrigerator is too close,” Taglietti quipped. “I read somewhere that the 19 of Covid-19 are the number of pounds that people will gain on average, by working from home.”
When Endpoints News interviewed Taglietti this time last year, he relayed his experience that antifungals were not a priority in Washington and that there were not adequate incentives in place to encourage development efforts.
Since then, the CDC has put Candida auris in its list of urgent threats, and the Covid-19 outbreak, for better or for worse, has put the spotlight on how devastating infectious diseases can be.
At the moment, organizations like NIH or BARDA or FDA in Washington are all squarely focused on Covid-19, and rightly so — it is a “powerful reminder” that anti-infectives need to be continually developed, Taglietti said.
“And I do believe that there will be a renewed awareness and renewed appreciation of what anti-infective companies are doing,” he said. “There will be more support from the public, policy lawmakers, investors and also Big Pharma.”
Social: Marco Taglietti via YouTube