CD101 IV Overview
CD101 IV is a novel molecule in the echinocandin class of antifungals. We are initially developing CD101 IV for the treatment of systemic Candida infections. These infections include candidemia and related cases of invasive candidiasis, which are fungal infections associated with high mortality rates. The current treatment alternatives for systemic fungal infections, including polyenes, azoles and currently-approved echinocandins, have limitations that may be addressed by novel antifungals.
CD101 IV has a prolonged half-life which, in contrast to all other echinocandins, may allow for once-weekly IV therapy. This pharmacokinetic profile may overcome the limitations of the current standard of care by potentially offering the ability to treat resistant pathogens, allowing single-agent treatment across inpatient and outpatient settings, facilitating shorter and less costly hospital stays, improving compliance for outpatients and providing more convenient outpatient echinocandin treatment and prophylaxis regimens.
The U.S. Food and Drug Administration (FDA) has designated CD101 IV as a Qualified Infectious Disease Product (QIDP) with Fast Track status and orphan drug designation. The designations are for the use of CD101 IV in the treatment of candidemia and invasive candidiasis. The seven-year period of marketing exclusivity provided through orphan designation combined with an additional five years of marketing exclusivity provided by the QIDP designation positions CD101 IV for a total of 12 years of potential marketing exclusivity to be granted at the time of FDA approval.
A Current Candidemia Regimen
Potential CD101 IV Regimen
Based on clinical and preclinical results to date, we expect a single dose of CD101 IV to provide sufficient drug exposure for a period of seven days. In contrast, currently approved echinocandins are delivered by once daily IV infusions.
Systemic Candida Infections and the Current Standard of Care
According to a study reported in Clinical Infectious Disease (2009), candidemia has a mortality rate of 35% within 12 weeks of diagnosis. Further, it is estimated that each case of candidemia results in an additional 23 days of hospitalization and over $68,000 in treatment costs. The current treatment alternatives for systemic fungal infections, including polyenes, azoles and currently approved echinocandins, have limitations that may be addressed by novel antifungals. While these drugs are largely efficacious, they may cause severe side effects and are known to cause drug interactions that can limit their utility.
Echinocandins, introduced in 2001, are increasingly recommended for the treatment of fungal infections in the United States. The approved echinocandins, caspofungin, micafungin, and anidulafungin, are considered both well tolerated and safe relative to other antifungal drug classes. However, they must be administered daily by IV infusion, potentially extending the hospitalization of patients for the duration of therapy and limiting their use mainly to the hospital setting. Furthermore, the CDC reports that certain species of Candida are becoming increasingly resistant to available antifungals, such as the azoles and approved echinocandins. Learn about the market and opportunity >>
Pharmacokinetics and Prolonged Half-Life
Based on results from our single ascending dose trial, CD101 IV has a prolonged half-life of greater than 80 hours in humans. CD101 IV may thus be safely developed as a once-weekly IV therapy, allowing patients with candidemia to receive sufficient drug exposure in just two doses to cover fourteen days of treatment post-clearance of the active infection, which is the current recommended course of treatment.
Half-life of CD101 IV and Other Echinocandins
PK measurements marked with an asterisk are from assays conducted by us. Other values are from studies published by third parties. Based on clinical and nonclinical results to date, we expect a single dose of CD101 IV to provide sufficient drug exposure for a period of seven days.
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CD101 IV pharmacokinetic profile may overcome the limitations of the current standard of care by offering the following key benefits:
- Single-agent treatment: Rather than treating patients with an IV echinocandin followed by an oral azole solely to enable earlier hospital discharge, CD101 IV would enable extended single-agent echinocandin treatment for the full course of therapy, thereby enabling treatment that is consistent with current guidance in the United States and European Union.
- Shorter and less costly hospital stays: Physicians with access to a once-weekly echinocandin can potentially discharge appropriate patients earlier and thereby reduce hospital costs, which account for over 70% of the overall treatment cost of candidemia.
- Improved compliance: A once-weekly treatment of CD101 IV could facilitate compliance by eliminating the need for patients to return to a hospital or outpatient center for a daily dose of an IV echinocandin, and could eliminate the likelihood of patient non-compliance for those receiving oral step down therapy with a daily azole.
- Enabling or improving prophylaxis regimens: Some patients cannot receive azole prophylactic therapy due to drug interactions or poor tolerability. We expect that once-weekly CD101 IV therapy would provide for better prophylactic therapy on an outpatient basis, particularly for these patients.
- Potential to treat resistant or less-susceptible pathogens: We believe that CD101 IV can be used to treat some fungal infections caused by drug-resistant fungi, including those currently resistant to echinocandins, due to its higher drug exposure early in the course of therapy. We expect that this higher exposure early in the course of disease will improve outcomes in infections caused by both susceptible and less-susceptible pathogens.
Activity Against Resistant Strains
We believe that CD101 IV can address important unmet medical needs in patients with candidemia caused by both susceptible and azole- or echinocandin-resistant Candida, as well as in patients at risk of invasive fungal infections who cannot take azole or polyene antifungals because of drug interactions or safety concerns.
The high potency of CD101 IV, combined with the very high Cmax and drug exposure associated with the front-loaded once weekly dosing regimen, may result in improved efficacy in treating less-susceptible Candida infections.
We have completed two Phase 1 clinical trials for CD101 IV: a single ascending dose trial (SAD) and a multiple ascending dose (MAD) trial. These studies established the safety and PK profile of CD101 IV in healthy subjects, demonstrating that up to 400 mg once weekly for 3 consecutive weeks was safe and well tolerated.
Key results of CD101 IV multiple ascending dose trial include:
- Safely achieved very high front-loaded plasma exposures potentially improving treatment outcomes
- Long half-life enables weekly dosing
- Well tolerated across entire dose range
- No serious or severe adverse events
- No clinical chemistry, hematology or ECG safety concerns
These data support the continued development of CD101 IV for the treatment of candidemia and invasive candidiasis in the inpatient and outpatient settings. Based on the results from the Phase 1 studies, we are conducting an international Phase 2 trial of CD101 IV in candidemia called STRIVE.
STRIVE: Phase 2 Study Design
STRIVE is a Phase 2, multicenter, randomized, double-blind trial evaluating the safety, tolerability and efficacy of CD101 IV compared to intravenous caspofungin followed by oral fluconazole therapy (i.e., “step-down” therapy) in patients with candidemia. In two arms of the trial, patients will receive either 400 mg of CD101 IV once weekly for two weeks or 400 mg for the first week followed by 200 mg once weekly for the second week. For both arms, a third weekly dose may be administered if medically indicated. In the comparator arm, patients will receive caspofungin according to the approved prescribing information. Oral step-down fluconazole therapy can be administered in the comparator arm following IV caspofungin therapy based on medical judgement and if specific clinical and microbiological criteria are met. Cidara plans to enroll 90 patients in STRIVE across the United States and Europe.
ASH 2016 | San Diego, CA | December 2016
- Pharmacokinetics, Safety, and Target Attainment of Single and Multiple Doses of CD101 IV
- Efficacy of CD101, a Novel Echinocandin, in Mouse Models of Aspergillosis and Azole-Resistant Disseminated Candidiasis
- Efficacy of CD101, a Novel Echinocandin, in Prevention of Pneumocystis Pneumonia (PCP): Thwarting the Biphasic Life Cycle of Pneumocystis
ASM Microbe | Boston, MA | June 2016
- Safety and Pharmacokinetics of Multiple Doses of CD101 Injection: Results from a Phase 1, Dose-escalation Study [LB-057]
- Pharmacological Basis of CD101 Efficacy: Exposure Shape Matters [SUNDAY-505]
- Tissue Distribution and Pharmacokinetics of CD101 in an Immunocompetent Mouse Model of Invasive Candidiasis [Presentation]
- Prevention of Pneumocystis Pneumonia by the Long Acting Echinocandin CD101 [Presentation]
- Efficacy of a Novel Echinocandin, CD101, in a Mouse Model of Azole-Resistant Disseminated Candidiasis [Presentation]
Advances Against Aspergillosis | Manchester, UK | March 2016
ICAAC/ICC | San Diego, CA | September 2015
- Preclinical Evaluation Shows CD101, a Novel Echinocandin, is Highly Stable with No Hepatotoxicity in Rats [A-015]
- Evaluation of CD101 Glucan Synthase Inhibition, MIC Values and Mutant Prevention Concentrations Against Echinocandin-Susceptible and -Resistant Candida spp. [F-747]
- Efficacy of CD101 to Treat Echinocandin-Resistant Candida albicans in a Murine Model of Invasive Candidiasis [F-748]
- Structure-Activity Relationship of a Series of Echinocandins and the Discovery of CD101, a Highly Stable and Soluble, Once-Weekly Novel Echinocandin [F-750]
- Determination of CD101 Spontaneous Mutation Frequencies and Underlying Resistance Mechanisms in Candida spp. [F-753]
- Characterization of Resistance Following Serial Passage of Candida spp. in the Presence of CD101 [F-754]
- Prolonged Efficacy Following One Dose of a Novel Echinocandin, CD101, in a Neutropenic Mouse Model of Disseminated Candidiasis [F-761]
- Activity of a Long-Acting Echinocandin (CD101) and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates [M-849]
- Evaluation of the In Vitro Activity of CD101, a Novel Echinocandin, and Comparators Against Recent Clinical Isolates of Candida spp. [M-850]
- Evaluation of Disk Diffusion Susceptibility Testing for CD101, a Novel Echinocandin, Against Candida spp. [M-851]
- Evaluation of the Fungicidal Activity of CD101, a Novel Echinocandin, and Comparators Against Recent Clinical Isolates of Candida spp. [M-852]
ICAAC | Washington, DC | September 2014
- Safety and Pharmacokinetics of CD101 IV, a Novel Echinocandin, in Healthy Adults Antimicrob Agents Chemother | February 2017 | Volume 61, Issue 2
- Pharmacokinetics of the Novel Echinocandin, CD101, in Multiple Animal Species Antimicrob Agents Chemother | Advance Access | January 2017
- Preclinical Evaluation of the Stability, Safety and Efficacy of CD101, a Novel Echinocandin Antimicrob Agents Chemother | November 2016 | Volume 60, Issue 11
- Activity of a Long-Acting Echinocandin (CD101) and Seven Comparator Antifungal Agents Tested Against a Global Collection of Contemporary Invasive Fungal Isolates in the SENTRY (2014) Antifungal Surveillance Program Antimicrob Agents Chemother | Advance Access | January 2017
- CD101, a novel echinocandin with exceptional stability properties and enhanced aqueous solubility J Antibiotics | February 2017 | Volume 70, Issue 2
- Structure-Activity Relationships of a Series of Echinocandins and the Discovery of CD101, a Highly Stable and Soluble Echinocandin with Distinctive Pharmacokinetic Properties Antimicrob Agents Chemother | February 2017 | Volume 61, Issue 2
- Activity of a long-acting echinocandin, CD101, determined using CLSI and EUCAST reference methods, against Candida and Aspergillus spp., including echinocandin- and azole-resistant isolates J Antimicrob Chemother | October 2016 | Volume 71, Issue 10
- Characterization of in vitro resistance development to the novel echinocandin, CD101, in Candida species Antimicrob Agents Chemother | September 2016 | Volume 60, Issue 10
- CD101: a novel long-acting echinocandin Cell Microbio | September 2016 | Volume 18, Issue 9
The safety and single-dose pharmacokinetics of CD101 IV: results from a phase 1, dose-escalation study ECCMID | Amsterdam, Netherlands | April 11, 2016