dm+d

Unassigned

New Medicines

Invasive Candida infection

Information

New molecular entity
Scynexis
Scynexis

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Antifungal drugs (05.02)
Beta-1,3-D glucan synthetase inhibitors
The rate of candidaemia in England, Wales and N.Ireland was 3.3 per 100,000 population in 2018. The three most frequently identified Candida species from blood were C.albicans (40%), C. glabrata (29%) and C. parapsilosis (11%). [11]
Invasive Candida infection
Oral

Invasive Aspergillus infection, for use in combination with oral voriconazole

Information

Licence extension / variation
Scynexis
Scynexis

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

Beta-1,3-D glucan synthetase inhibitor
Invasive aspergillosis is uncommon and occurs primarily in immunocompromised people. In the UK, the Fungal Infection Trust estimated in August 2017 that there were ~2900 cases of Invasive aspergillosis excluding critical care pts in 2017. Its estimated that >50% of pts with IA die, even with treatment.[11,12]
Invasive Aspergillus infection, for use in combination with oral voriconazole
Oral

BrexafemmeVulvovaginal candidiasis (VVC) and recurrent VVC - treatment

Information

Brexafemme
Licence extension / variation
Scynexis
Scynexis

Development and Regulatory status

None
None
Approved (Licensed)
Jun 21Launch of Brexafemme in the US is planned for Aug 21 with a wholesale acquisition cost of $475 per course (four tablets) [19]
Jun 21Approved in US [18].
Dec 20US FDA accepted the New Drug Application (NDA) of ibrexafungerp for the treatment of VVC and granted Priority Review with a target action date of June 1, 2021. [16,17]
May 20lead indication - the company plans to file a NDA with the FDA for this indication 2H 2020, with a submission for prophylaxis 2H 2021; EU timelines not stated, but commercialisation outside the US likely to be through partnering with other companies [14].
Apr 20Company announce plans to submit NDA to the US FDA during H2 2020. [15]
Jan 20 PIII trial underway and will complete Jun 2020.[13]
Jul 19 A PIII trial is being planned (CANDLE) to evaluate ibrexafungerp for the prevention of recurrent VVC.[12]
May 18US FDA granted QIDP and Fast Track Designation to SCY-078 to treat vulvovaginal candidiasis (VVC) and recurrent VVC. [7]

Category

Beta-1,3-D glucan synthetase inhibitor
Between 29% and 49% of women surveyed in Europe and the US reported diagnosed vaginal yeast infection during their lifetime and 9% reported recurrent vaginal and vulval candidiasis. Around 10-20% of women have asymptomatic vaginal colonisation with Candida spp. and do not need treatment.[10]
Vulvovaginal candidiasis (VVC) and recurrent VVC - treatment
Oral

Trial or other data

Nov 21PIII VANISH 306 RCT (n=272) found that compared to placebo, a 1 day course (300mg BD) of ibrexafungerp increased clinical cure (63.3 v 44.0%;p=0.007) & mycological eradication (58.5 v 29.8%;p<0.001) with symptom resolution sustained at day 25 (73.9 v 52.4%;p=0.001) [20].
Apr 20Positive results from the PIII VANISH 306 trial showed that 63.3% of ibrexafungerp-treated pts met the primary endpoint of clinical cure after 10 days following a single-day 600mg dose regimen. Mycological eradication was attained by 58.5% of ibrexafungerp-treated pts met the (secondary endpoint). [15]
Apr 20Positive detailed results from the PIII VANISH 303 trial (n=376) available. Pts received either oral ibrexafungerp (2 x 300mg 12 hours apart) or placebo in a 2:1 ratio. Clinical cure (complete resolution of all signs and symptoms at day 10) for ibrexafungerp was 50.5%, showing highly statistically significant superiority to placebo (p=0.001). Mycological eradication (secondary endpoint) in the ibrexafungerp gp was 49.5%, also showing superiority to placebo (p<0.001). Oral ibrexafungerp was safe and well tolerated. Severe and serious adverse events (AEs) were rare, with more cases reported in the placebo group. [15]
Jan 20PIII CANDLE multicentre, randomized, double-blind, placebo-controlled study of ibrexafungerp vs. placebo in ~320 women in the USA with recurrent VVC is underway. Women will be randomised to receive oral fluconazole (150 mg every 72 hours for 3 doses) followed by oral ibrexafungerp (300 mg BID on day 1 then every 4 weeks for 6 days) or matched placebo. The primary outcome measure is the percentage of women with documented clinical success at week 24. The estimated primary completion date is Jun 2021.[13]
Nov 19Scynexis announce positive results from PIII VANISH-303 study. Ibrexafungerp achieved highly statistically significant superiority over placebo (p≤0.001) for complete resolution (score of 0) at the Day-10 test-of-cure visit [13].
Jul 19The PIII VANISH 306 study (NCT03987620) is recruiting up to 336 pts to evaluate the efficacy and safety of oral ibrexafungerp vs. placebo in pts with acute VVC. The estimated primary completion date is March 2020.[11]
Jun 19A PIII study (NCT03734991) is recruiting up to 366 pts to evaluate the efficacy and safety of oral ibrexafungerp vs. placebo in pts with acute VVC. This is part of the VANISH trial programme. The estimated primary completion date is Dec 19.[11,12]
May 18A PIIb randomised, double-blind, active comparator controlled dose-finding study (DOVE, NCT03253094) of oral ibrexafungep vs. oral fluconazole in 186 pts With acute VVC (DOVE) demonstrated optimal combination of overall clinical and mycological activity and favorable tolerability at a dose of ibrexafungerp 600mg. At Day 10 test-of-cure (TOC) visit, in the mITT population, clinical cure was indicated in 52% of pts on ibrexafungerp 600mg vs. 58% on fluconazole (FLU) with a comparable mycological eradication rate of 63% in both arms. At day 25, the clinical cure rate in the ibrexafungerp 600mg arm reached 70% vs. 50% in the FLU arm. Rescue antifungal therapy was inidicated in 4% of pts on ibrexafungerp 600mg vs 29% of pts in the FLU arm (29%). [12]