WTF Is Ibrexafungerp?
In June 2021, the antifungal medication ibrexafungerp, known under the brand name Brexafemme, was approved by the FDA for medical use in the United States for the treatment of vulvovaginal candidiasis (vaginal yeast infections). Notably, it is also the first approved drug in a novel antifungal class to receive FDA approval in more than 20 years.
Vaginal yeast infections affect more than 1 million women each year in the U.S., and symptoms include "intimate itching, burning and odor [that] can affect a woman's quality of life, from intimate relationships to even work performance and interactions with family and friends," said Betsy Greenleaf, D.O., FACOG, the first board-certified urogynecologist in the U.S.
"It is more than just an itch. It can affect mood, comfort and self-esteem," Greenleaf continued. "Yeast also likes warm, dark, wet environments, such as the vagina. Basically, a yeast infection is merely just an overgrowth of these organisms that are naturally all around us."
Brexafemme is not available yet, so information on the medication is almost entirely limited to the clinical trials conducted by the drug's manufacturer, SCYNEXIS, and the information found on its website.
The American College of Obstetricians and Gynecologists (ACOG) declined requests for an interview, stating, "Because this product is so new, ACOG has not had an opportunity to conduct our clinical committee review of the peer-reviewed evidence about it yet, so, unfortunately, we are unable to accommodate an interview request about it, as we have no organizational position."
What makes ibrexafungerp different from other antifungal medications?
All of the antifungal medications currently on the market to treat yeast infections are azoles, such as clotrimazole, terconazole and fluconazole. Azole antifungals work by stopping cell membrane formation by blocking the enzyme 14-ɑ demethylase and decreasing the formation of ergosterol, a vital component of the fungal cell membrane.
"The problem," Greenleaf explained, "is that, like bacteria, yeasts have gotten smart and become resistant to many of the antifungals that we have on the market. Resistant yeast can be very frustrating to treat for both patient and physician."
Additionally, azoles are "fungistatic, meaning they inhibit the growth of yeast, they don't directly kill it," stated Jen Gunter, OB-GYN and author of "The Vagina Bible," in her article about ibrexafungerp. This may be why some women have recurring yeast infections—because their medication did not fully eradicate the issue.
It's the first drug in a novel antifungal class to receive FDA approval in more than 20 years.
Ibrexafungerp, on the other hand, is a triterpenoid antifungal that works differently than azoles. Rather than blocking 14-a demethylase, ibrexafungerp is a novel glucan synthase inhibitor. It is also fungicidal, so it actually kills a broad range of yeast species, including azole-resistant strains, according to SCYNEXIS' press release.
For these reasons, Greenleaf and SCYNEXIS see ibrexafungerp as a solution for those who experience recurrent yeast infections and have found previous medications ineffectual.
"As of now, there are no yeasts [that are] resistant to the medication [ibrexafungerp], but it could happen over time as it does with other medications and natural selection," explained Greenleaf. "Brexafemme represents another tool in our toolbox."
How fast and effective is ibrexafungerp?
Yeast infections affect some women more frequently than others, notably "those who are currently taking or have recently taken a course of antibiotics, those who are pregnant, those with diabetes, those with a weakened immune system and those who use oral contraceptives," explained Emily Bintrim, Pharm.D., a Pittsburgh-based pharmacist.
Brexafemme is meant to be delivered as just two 300 mg doses, both taken on the same day. A single dose of fluconazole, meanwhile, can also be effective within one day for mild cases. However, in more severe cases, fluconazole might be prescribed as three doses spaced three days apart. This means Brexafemme could potentially be a much faster-acting alternative.
"In its clinical studies, ibrexafungerp was shown to be more effective [than azoles] at keeping patients infection-free after 25 days," said Bintrim. "The clinical trials had a modest sample size, so more studies will have to be done to conclusively say one agent is better than the other."
How much will ibrexafungerp cost?
In a call with analysts, SCYNEXIS' chief commercial officer, Christine Coyne, confirmed the drug's wholesale price (before insurance) as $475, a substantially higher amount than an equivalent dose of generic fluconazole, which costs $30 on average, and potentially less with a coupon.
"The final cost for Brexafemme is based on extensive market research and input from several key stakeholders, including healthcare providers and patients," Coyne told me. "It is also reflective of the differentiating characteristics of Brexafemme, which has a different mechanism of action, killing the fungus causing the yeast infection."
"We believe the rate of recommendation for Brexafemme will be strong, as healthcare providers are eager for a new option to offer their patients."
Vaginal yeast infections affect more than 1 million women each year in the U.S.
Bintrim was less confident in the immediate rate of recommendation, however. "Likely, it would not be approved [by insurance providers] unless the patient tries another option first or has a compelling clinical reason for the use of this medication," she explained. "I think it will find its place in the treatment of vaginal yeast infections. It's a good option in azole-resistant strains."
Ultimately, health insurance providers will be the determining factor in how widely Brexafemme is utilized.
Possible interactions and side effects
Ibrexafungerp interacts with a host of other medications, including clarithromycin, diltiazem, verapamil, phenobarbital, phenytoin and Saint John's Wort. Issues can also arise when the medication is combined with grapefruit juice.
SCYNEXIS warns in its prescribing information that women who are pregnant should not take the drug due to the risk of harm to the unborn baby. Side effects of the drug include loose stools, nausea, stomach pain, dizziness and vomiting. Current yeast infection medications can produce similar side effects.
Based on current data, Brexafemme might end up being a majorly beneficial medication for women with stubborn or recurring yeast infections. SCYNEXIS expects Brexafemme to hit shelves in the latter half of 2021, but no official date has been announced.
"This is the first treatment innovation for yeast infections in over 25 years," Coyne said. "Brexafemme is truly a different approach to treating yeast infections—especially for women that have had experience with other treatment options in the past."