Candidiasis: Developing Drugs for Treatment
2015-566 Vulvovaginal Candidiasis: Developing Drugs Treatment Draft Guidance for Industry
2016-09-21 2016-10-24
FDA-2016-D-1662-0004 FDA-2016-D-1662-0006
04:00:00 04:00:00
https://api.regulations.gov/v4/comments/FDA-2016-D-1662-0004 https://api.regulations.gov/v4/comments/FDA-2016-D-1662-0006
Anonymous Anonymous
Anonymous Anonymous
September 8, 2016Division of Dockets Management (HFA-305)Food and Drug Administration5630 Fishers Lane, Room 1061Rockville, MD  20852RE:Docket No. FDA-2016-D-1662Comments on FDAs Draft Guidance for Industry: Vulvovaginal Candidiasis: Developing Drugs for TreatmentDear Sir / Madam:On behalf of SCYNEXIS, Inc., we respectfully submit comments on FDAs Draft Guidance for Industry Vulvovaginal Candidiasis: Developing Drugs for Treatment. SCYNEXIS, Inc. is a pharmaceutical company committed to the development and commercialization of novel anti-infectives to address significant unmet therapeutic needs. Our lead product candidate, SCY-078, is a novel class, broad spectrum IV and oral antifungal that is a semi-synthetic triterpene derivative of the natural product enfumafungin for the treatment of serious and life-threatening invasive fungal infections, such as invasive candidiasis and invasive aspergillosis, including multidrug-resistant pathogens.  SCY-078 is also in development for Vulvovaginal Candidiasis (VVC) and recurrent VVC. Within Section II, B, 3. (line 105) of the proposed guidance, normal vaginal pH is described as: greater than or equal to 4.5.  SCYNEXIS, Inc. respectfully recommends replacing the proposed text as follows:replace greater than or equal to 4.5 with lesser than or equal to 4.5 Reference is made to Sobel et al, Lancet 2007; 369: 1961-71 (enclosed). We thank you for the opportunity to comment. Please contact me by telephone at 201-884-5471 or by email at david.angulo@scynexis.com if you have any questions concerning these comments.Sincerely,David Angulo, MDChief Medical Officer, SCYNEXIS, Inc.Enclosure: Sobel et al. 2007 September 29, 2016Division of Dockets ManagementFood and Drug Administration5630 Fishers LaneRoom 1061, HFA-305Rockville, MD 20852Re:Draft Guidance for Industry - Vulvovaginal Candidiasis: Developing Drugs for Treatment Docket ID: FDA-2016-D-1662To Whom It May Concern:Cidara Therapeutics Inc. (Cidara) is pleased to submit comments in response to the Food and Drug Administrations new draft guidance titled: Vulvovaginal Candidiasis: Developing Drugs for Treatment (July 2016), Docket ID: FDA-2016-D-1662. Cidara thanks the FDAs Division for Anti-Infective Drug Products for providing sponsors developing therapies for the treatment of Vulvovaginal Candidiasis (VVC) with a revised guidance replacing the previously withdrawn guidance from 1998 (Draft Guidance for Industry - Vulvovaginal Candidiasis: Developing Antimicrobial Drugs for Treatment, July 1998).Cidara is a clinical stage biotechnology company developing novel anti-infectives including immunotherapies for the treatment of serious and life-threatening infections. Cidara is developing a treatment for medically significant Vulvovaginal Candidiasis (VVC) infections. Accordingly, Cidara has a unique stake in regulatory guidance pertaining generally to womens health and specifically to drug development for the treatment of VVC. We are providing 3 comments to the draft guidance for your consideration.1. The stated focus of the draft guidance is for developing antifungal drugs for the treatment of uncomplicated VVC (I. Introduction). Although important clarifications and definitions are provided in this guidance to assist sponsors developing drugs for the treatment of women suffering from uncomplicated infections, the definitions for uncomplicated and complicated VVC remain unclear.  This guidance represents an important first step.  An important next step is the provision of a draft guidance for developing therapies for the treatment of women suffering from complicated VVC.  Cidara urges the FDA to issue guidance as soon as possible to address this important medical need. 2. The guidance states that ...the primary efficacy endpoint should be clinical cure, defined as the absence of all signs and symptoms of VVC (II.B.8 Efficacy Endpoints). In the previous guidance from 1998, Clinical Cure was defined in the context of severity of disease.  For subjects with mild infections (any sign or symptom with a score of 1 or 2 at entry) scores of 0 were recommended at the Test-of-Cure visit.  For subjects with moderate to severe infections (any sign or symptom of 3 or more at entry) scores of 0 or 1 were recommended at the Test-of-Cure visit.  Cidara believes that it is reasonable to consider reinstituting the previous scoring system for a couple of reasons.  First, many normal, healthy women have baseline symptoms of itching, burning, or irritation.  Using an absence of all symptoms and signs to define clinical cure results in an inability for clinical cure to be achieved in these subjects even if the subjects clinical status returns to her baseline.  Second, residual symptoms from more severe infections may take longer to resolve, which is even more impactful given the earlier Test-of-Cure timepoint at Day 7-14.  Utilizing scores of 0 or 1 at the Test-of-Cure visit would allow for instances where mycological eradication has been demonstrated but where residual symptoms may take a little longer to resolve  The primary concern in both these scenarios is misclassification of outcome - marking a subject as a clinical failure when the subject should be a cure.  Under the current guidance, a change from 12 to 1 in one subject on Day 7 would be the same as a change from a 12 to 11 in another subject - both would be clinical failures.  We are concerned that this resulting misclassification of the outcome would make demonstrating superiority more difficult, even where there are clearly differences in how a patients feels and functions between the two study arms. Therefore, Cidara recommends keeping the previous recommendation for clinical cure as provided for in the 1998 guidance.3. The new guidance provides for the addition of safety information into the overall safety database from patients treated with the same therapy for other infectious disease indications (II.A.3 Safety Considerations).  The guidance also recommends for drugs administered topically that the focus should be on both local and systemic toxicity. Cidara agrees that for topical products where systemic exposures are low, the inclusion of safety data into the overall safety database from systemic exposure studies is valuable in providing an overall assessment of safety. Sincerely,Carmen M. Betancourt-Riche, MBA,  Senior Vice President, Regulatory and Quality AssuranceTaylor Sandison, MD MPH, Chief Medical Officer (Acting), Vice President, Clinical DevelopmentCidara Therapeutics, Inc., 6310 Nancy Ridge Drive, Suite 101, San Diego, CA 92121