Lupin Pharmaceuticals Inc. (Lupin) announced positive results from its phase 3 trial assessing the efficacy and safety of secnidazole (Solosec) in female patients with trichomoniasis. Although trichomoniasis is common in the United States, the risk of being infected with the infection is nearly 10 times higher for African American women compared with non-Hispanic white women.
Lupin Pharmaceuticals Inc. (Lupin) announced positive results from its phase 3 trial assessing the efficacy and safety of secnidazole (Solosec) in female patients with trichomoniasis. Trichomoniasis is the most prevalent non-viral and curable sexually transmitted infection (STI) in the United States. An estimated 3.7 million people live with the infection, the CDC reports.
Although the STI is common in the United States, the risk of being infected with trichomoniasis is nearly 10 times higher for African American women compared with non-Hispanic white women.Trichomoniasis is 4 to 5 times more prevalent in women than men and is associated with adverse reproductive health outcomes such as infertility, preterm birth, and a 2- to 3-fold increased risk of HIV infection. Symptoms can include discomfort with urination and vaginal discharge. However, “most infected persons (70%-85%) have minimal or no symptoms, and untreated infections might last for months to year.”
Current treatments for the STI include oral doses of metronidazole (Flagyl) or tinidazole (Tindamax). Men and women can develop trichomoniasis and, if one individual tests positive, both partners need treatment. Metronidazole and tinidazole are indicated for male and female use.
“Labelling discussions will take place after FDA review of the clinical data,” Lupin stated when asked about the treatment’s efficacy in males. Additional clinical trials for secnidazole are under evaluation and consideration, according to the company.
However, the current trial “demonstrated a clinically and statistically significant response rate, or microbiological cure, in patients dosed with Solosec as compared to placebo (P <.001).”
Secnidazole is currently approved by the FDA for bacterial vaginosis (BV) in adult women. Although full trial results are not yet available, Lupin plans to submit a supplemental New Drug Application (sNDA) to the FDA for the treatment of trichomoniasis in the second half of 2020. Additional data is expected to be released to support the filing.
The infection is caused by a protozoan parasite called Trichomonas vaginalis (T. vaginalis). “Up to 53% of women with HIV infection also have T. vaginalis, which is associated with a significantly increased risk of contracting pelvic inflammatory disease (PID),” according to the CDC.
Trial participants completed test-of-cure (TOC) visits within 6 to 12 days after trichomoniasis confirmation. The primary endpoint of microbiological cure was defined as a negative T. vaginalis culture.
In the per-protocol population, the cure rate was 94.9% (56/59) for secnidazole compared with 1.7% (1/60) for placebo (P <.001). The most commonly reported adverse events among participants were vulvovaginal candidiasis (2.7%) and nausea (2.7%).
A separate, modified intent-to-treat (mITT) population (all randomized subjects who were culture positive for T. vaginalis and negative for gonorrhea and chlamydia at baseline) exhibited similar positive results: 92.2% (59/64) of secnidazole recipients achieved endpoint versus 1.5% (1/67) for placebo (P<.001). One study1 conducted between 2013 and 2016 found prevalence of trichomoniasis was 9.6% for African American women, 1.4% for Hispanic women, and 0.8% for non-Hispanic white women. Racial disparities present in infected populations appear to exceed 2 those observed for chlamydia, herpes simples virus (HSV) 2, and human papillomavirus.
Among women, increased poverty level, lower educational attainment, unmarried status, and having been born in the United States were significantly associated with T. vaginalis infection. Additional risk factors include “younger age at sexual debut, greater number of lifetime and/or past 12 months sex partners, and chlamydia infection in the past 12 months.”
In 2018, the infection was classified as a “neglected” STI by some researchers, due to the fact that there are no established T. vaginalis screening, surveillance, or control programs for women or men in the United States.
Although the CDC only recommends routine trichomoniasis screening of asymptomatic women with HIV, researchers feel scaling up national efforts to combat the STI should include “routine T. vaginalis screening programs among women presenting to STI clinics across the country.”
Socioeconomic determinants of health, including reduced access to healthcare, may partially contribute to racial disparities present in rates of trichomoniasis. The asymptomatic nature of the STI could also inhibit individuals from seeking out testing or treatment.
“From a social justice lens, it cannot be underscored that structural racism could be a contributing factor; neighborhood social disorganization has been shown to be significantly associated with T. vaginalis infection,” said Aaron Tobian, MD, PhD, a lead author of a 2018 study 3 investigating prevalence of the STI in the United States.
High burden of infection in the black population may also be due to differences in sexual network characteristics (e.g., assortative mixing—favoring sexual partners of the same race), differences in individual-level sexual risk behaviors (e.g., higher numbers of sexual partners), and biological differences in susceptibility to infection.
However, researchers found racial disparities in T. vaginalis infection persisted despite adjustment for the number of sexual partners in the past year. This finding, in addition to the STI’s exceedance of perceived disparities present in other infections, points to additional underlying factors besides induvial-level sexual risk behaviors.
Although there is insufficient empirical evidence that increased screening can lead to epidemic control or reductions in racial dipartites, “it would be an injustice to the black population to continue to ignore this STI until such evidence is available,” researchers said. “Increased public health action is needed to eliminate the stark racial disparities in T. vaginalis infection and achieve racial equity in sexual health,” authors conclude.
1. Flagg EW, Meites E, Phillips C, et al. Prevalence of trichomonas vaginalis among civilian, noninstitutionalized male and female population aged 14 to 59 Years: United States, 2013 to 2016. Sex Transm Dis. 2019; 46(10):e93-e96. doi: 10.1097/OLQ.0000000000001013.
2. Muzny CA. Why does trichomonas vaginalis continue to be a ‘neglected’ sexually transmitted infection? Clin Infect Dis. 2018; 67(2):218-220. doi: 10.1093/cid/ciy085.
3.Patel EU, Gaydos CA, Packman ZR, et al. Prevalence and correlates of trichomonas vaginalis infection among men and women in the United States. Clin Infect Dis. 2018; 67(2): 211-217. doi: 10.1093/cid/ciy079.