- Solosec™ (secnidazole) oral granules met all primary and secondary endpoints for bacterial vaginosis (BV)
- Second pivotal data set submitted to FDA as part of New Drug Application undergoing priority review to be published
- If approved, Solosec™ will be the first and only single-dose oral therapy for BV, the most common gynecological infection in the U.S.
Newark, NJ, September 6, 2017 – Symbiomix Therapeutics today announced the publication of positive phase 3 data from a pivotal clinical trial of investigational single-dose Solosec™ (secnidazole) oral granules for the treatment of bacterial vaginosis (BV).  Data from the randomized, double-blind, placebo-controlled, multi-center study (SYM-1219-301) were published ahead of print in the online version of the American Journal of Obstetrics & Gynecology. Solosec™ is a potent, next-generation, 5-nitroimidazole antibiotic with enhanced pharmacokinetic properties, and is the first and only single-dose oral therapy in development for BV, the most common gynecological infection in the U.S. 
BV is the most common vaginal infection in the U.S. among women ages 14-49 years old, with more than four million treated annually. One in three women have BV, affecting more than 21 million in the U.S. each year. More than 50 percent of women treated for BV have a recurrence within 12 months. [2,3,4,5,6]
“The current recommended treatment options mainly consist of multi-dose therapy, which can lead to issues with medication adherence,” said Jane R. Schwebke, MD, Professor of Medicine and Infectious Diseases at the University of Alabama at Birmingham and lead author of the publication. “The data supports secnidazole as an effective and well-tolerated potential single-dose option for BV that will be a welcome advance in the treatment of this prevalent gynecologic infection.”
In the SYM-1219-301 study, women with BV were randomized to 2 g secnidazole or placebo, each administered as a single oral dose. The 2 g dose of secnidazole proved superior to placebo on all primary and secondary outcomes and was well tolerated.
In the modified intent-to-treat (mITT) population of 189 women, clinical outcome responder rates were 53.3% for 2 g secnidazole compared with 19.3% for placebo (p<0.001). The clinical outcome responder rate analysis was 58.9% for 2 g secnidazole compared with 24.6% for placebo (p<0.001) when women with abnormal discharge that is inconsistent with BV were included as clinical outcome responders. Clinical cure rates based on the 2016 FDA guidance of 7-14 days after treatment were 64.0% for 2 g secnidazole compared with 26.4% for placebo. Based on the investigator’s clinical assessment at the test of cure, significantly more patients receiving single-dose secnidazole 2 g compared to placebo required no additional BV treatment (68.0% vs 29.6%; P<0.001). The overall adverse event rate was 34.4% for single-dose secnidazole 2 g compared to 21.9% for placebo. Most adverse events were mild or moderate in intensity and non-serious. 
“The study results support the potential of Solosec™ as a new treatment option for the millions of women in the U.S. suffering with bacterial vaginosis,” said David L. Stern, Symbiomix CEO. “These findings encourage our efforts to expand the development of Solosec™ and we are continuing to work with U.S. regulatory authorities to bring innovative therapies to market for prevalent gynecologic infections that can have serious health consequences.”
The U.S. Food and Drug Administration (FDA) accepted the New Drug Application (NDA) for Solosec™ (secnidazole) oral granules in March 2017. In accordance with the FDA’s priority six-month review designation, the agency has established a user-fee goal date under the Prescription Drug User Fee Act (PDUFA) of September 2017.
About Trial SYM-1219-301
SYM-1219-301 is a phase 3, randomized, double-blind, dose-ranging, placebo-controlled, multi-center study to evaluate Solosec™ for the treatment of BV. In the trial, women with BV who met all Amsel criteria (characteristic discharge; pH 4.7 or greater; 20% or greater clue cells; positive whiff test) were randomized 2:1 at 21 U.S. centers to 1 or 2 g secnidazole compared with placebo. The primary endpoint was the proportion of clinical outcome responders (normalization of discharge, amine odor and clue cells) 21–30 days after treatment. Secondary endpoints included clinical cure rates (normalization of discharge, amine odor and clue cells) assessed 7–14 days after treatment and test of cure 21–30 days after treatment. Based on the 2016 FDA draft guidance, patients with baseline Nugent scores 7–10 were evaluated for clinical cure (normalization of discharge, amine odor and clue cells) 7–14 days after treatment. The modified intent-to-treat was used for efficacy analyses and included all randomized patients who met the enrollment criteria. 
Between May 4, 2015 and August 26, 2015, 125 and 64 patients were assigned 2:1 to single-dose secnidazole 2 g and placebo, respectively. The modified intent-to-treat population included 189 women (mean age was 32 years; 77.2% with 3 or less BV episodes in the previous 12 years) with the mean baseline Nugent score of 8. Clinical cure rates were 58.9%, 53.3%, and 64.0% for 2 g secnidazole compared with 24.6%, 19.3%, and 36.4% for placebo. 
Treatment-emergent adverse events were reported in 20.0% of single-dose secnidazole 2 g–treated patients and 10.9% of placebo patients. Severe adverse events among single-dose secnidazole 2 g–treated patients included diarrhea and syncope (2 patients each) and dehydration, ectopic pregnancy, and vulvovaginal mycotic infection (1 patient each); of these events, both cases of diarrhea and the vulvovaginal mycotic infection were assessed as treatment-related. Two severe events, ectopic pregnancy and 1 case of syncope, also were serious; both events were assessed as unrelated to study drug. 
About Bacterial Vaginosis (BV)
BV is the most prevalent gynecological infection in the U.S. among women ages 14-49. [2,3] Today more than four million women are treated in the U.S. for BV annually.  More than 50 percent of women treated for BV have a recurrence within 12 months.  The U.S. Centers for Disease Control and Prevention (CDC) has stated that BV can cause serious health risks, including:
- Increasing the risk of HIV transmission;
- Increasing the risk of contracting other sexually transmitted diseases, such as chlamydia and gonorrhea, which, if untreated, may lead to pelvic inflammatory disease and infertility; and
- In pregnant women, increasing the risk of delivering a baby too early. 
BV disproportionately affects disadvantaged populations, including women of color, and may contribute to persistent disparities in women’s health outcomes. [8,9-]
BV has a significant impact on the work productivity and quality-of-life of affected women, with 60% of recurrent sufferers reporting a negative impact on work attendance, job performance and productivity, and 95% reporting a severe restriction in intimate partner relations. [10,11]
The current recommended regimen of a first-generation nitroimidazole requires twice-a-day dosing for seven days for a total administration of seven grams of drug. Adherence with the current leading therapy for the treatment of BV has been shown to be only approximately 50 percent.  Poor adherence to anti-infective therapy is a problem that increases with the length and complexity of the drug regimen, and can lead to treatment failures, recurrent disease and the more rapid development of resistant microorganisms. [1,2] These, in turn, may lead to higher health care costs, including increased out-of-pocket expenses, increased office visits and tests, additional treatment costs, and lost productivity. [1,3]
About Symbiomix Therapeutics, LLC
Symbiomix (sim-bye-OH-mix) is a biopharmaceutical company bringing innovative medicines to market for prevalent gynecological infections that can have serious health consequences. The Company’s lead investigational drug Solosec™ (secnidazole) oral granules, a potent, next-generation 5-nitroimidazole antibiotic, is anticipated to be the first and only single-dose oral treatment approved for bacterial vaginosis (BV). Symbiomix was founded in 2012 by a team of experienced industry professionals and entrepreneurs and is backed by three of the world’s leading healthcare venture capital firms: OrbiMed, F-Prime Capital Partners, and HBM Partners. Symbiomix is based in New Jersey, with additional offices in Maryland and Connecticut. Please visit https://symbiomix.com/ and follow the Company on LinkedIn and Twitter for more information.
- Schwebke, J.R., et al. (2017). “A Phase 3, Double-blind, Placebo-controlled Study of the Effectiveness and Safety of Single Oral Doses of Secnidazole 2 g for the Treatment of Women with Bacterial Vaginosis.” Retrieved from: http://www.ajog.org/article/S0002-9378(17)30964-X/fulltext
- Allsworth, J.E., Peipert, J.F. (2007). “Prevalence of Bacterial Vaginosis: 2001-2004 National Health and Nutrition Examination Survey Data.” Obstetrics & Gynecology 109:114-20.
- Koumans E, Sternberg M, Bruce C, et al. The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health. Sex Transm Dis. November 2007;34(11): 864-869.
- IMS Health, 2014
- Bradshaw, C.S., et al. (2006). “High Recurrence Rates of Bacterial Vaginosis Over the Course of 12 Months After Oral Metronidazole Therapy and Factors Associated with Recurrence.” J Infect Dis. Jun 1;193(11):1478-86.
- Bartley, J.B., et al. (2004). “Personal Digital Assistants Used to Document Compliance of Bacterial Vaginosis Treatment.” Sex Transm Dis 31(8): 488-491.
- Fiscella, K. (1996). “Racial Disparities in Preterm Births. The Role of Urogenital Infections.” Public Health Rep 111(2): 104-113.
- Payne et al. (2010). “Evidence of African-American Women’s Frustrations with Chronic, Recurrent Bacterial Vaginosis.” Jn AANP 22:101-108.
- Bilardi et al. (2013). “The Burden of Bacterial Vaginosis: Women’s Experience of the Physical, Emotional, Sexual and Social Impact of Living with Recurrent Bacterial Vaginosis.” PlusOne vol 8, issue 9.
- Kardas, P. (2002). “Once-Daily Dosage Secures Better Compliance with Antibiotic Therapy of Respiratory Tract Infections than Twice-Daily Dosage.” WONCA Europe 2002 Conference, London.
- Kardas, P., Bishai, W., (2006). “Compliance in Anti-Infective Medicine.” Adv Stud Med 6(7C):S652-S658.