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Cidara’s novel antifungal shows promise in phase 2 study

George Thompson
George R. Thompson

SAN FRANCISCO — Results from the phase 2 STRIVE trial show that the novel echinocandin rezafungin — formally known as CD101 — demonstrated comparable safety and efficacy to caspofungin for the treatment of invasive Candida fungal infections. The drug’s manufacturer, Cidara Therapeutics, said a phase 3 analysis is currently underway.

Study researcher George R. Thompson, MD, associate professor of medicine at the University of California, Davis, and an Infectious Disease News Editorial Board member, said in an interview that the pharmacokinetics of this echinocandin are novel, with a once-weekly dosing strategy that could be a huge benefit to patients with Candida.

“For a significant number of our patients with Candida glabrata, this could be a medication that they could receive before they go home, and they would essentially be done with therapy,” he said. “This could potentially get patients out of the hospital sooner.”

In STRIVE, patients aged 18 years or older with mycologically confirmed candidemia or invasive candidiasis, or both, were randomly assigned to receive IV rezafungin for up to 4 weeks dosed at either 400 mg weekly (Group 1; n = 33) or 400 mg on the first week and then 200 mg weekly thereafter (Group 2; n = 31), or standard care, which consisted of daily IV caspofungin with optional oral stepdown therapy after at least 3 days (Group 3; n = 28).

Thompson and colleagues tracked the number of treatment-emergent adverse events (TEAEs) across the three groups, and they defined overall success as a composite endpoint of clinical cure plus mycological success.

The researchers said there was a high number of indeterminate responses in Group 1 because of missing data points, so they conducted two analyses — one that included the indeterminate responses and one that excluded them. Thompson explained that the reason for the number of indeterminate responses was “a lack of comprehensive follow up” in the phase 2 trial. Healthy patients are often harder to follow up with, and those who did not show up were counted as treatment failures.

“This won’t be an issue in the phase 3 trial,” he added.

The researchers said they found no concerning safety trends. Study findings showed that the rate of TEAEs was 88.6% in Group 1, 94.4% in Group 2 and 81.8% in Group 3. Severe adverse events occurred in 37.1%, 27.8% and 39.4% of the groups, respectively.

The most common Candida species that was isolated was C. albicans (n = 45), followed by C. glabrata (n = 17), C. tropicalis (n = 15) and C. parapsilosis (n = 13).

Treatment efficacy was similar across all three groups. According to the researchers, the rate of overall success at day 5 was highest in Group 2 (67.7%), followed by Group 1 (57.6% with indeterminate responses and 65.5% without them) and Group 3 (53.6%).

At day 14, the rate of overall success was again highest in Group 2 (71%), followed by Group 3 (64.3%) and Group 1 (57.6% with indeterminant responses and 73.1% without them).

The overall mortality rate was 15.2% in Group 1, 9.7% in Group 2 and 17.9% in Group 3, the researchers said.

The researchers acknowledged the small sample size and that the findings will need to be confirmed, but they said the results support further clinical study of rezafungin.

Thompson mentioned that rezafungin will be studied in children as well. He also said that in addition to treating invasive fungal infections — which are a challenge in the ICU setting — the drug can be used as prophylaxis, particularly in the bone marrow transplant population.

With the emergence of fluconazole-resistant Candida species over the past decade or more, Thompson said rezafungin will be an important addition to the armamentarium.

“The unique pharmacokinetics parameters of rezafungin really has the potential for improved efficacy,” he said. “There’s a very low side-effect profile, just like other agents in the class. So, I think there’s a big advantage overall, and it should be a big step forward.” – by John Schoen

Reference:

Thompson GR, et al. Abstract 1718. Presented at: IDWeek; Oct. 3-7, 2018; San Francisco.

Disclosures: Thompson is an investigator for and reports receiving research support from Cidara. He also reports ties with Astellas, Mayne, Scynexis and Vical. Please see the abstract for all other authors’ relevant financial disclosures.

George Thompson
George R. Thompson

SAN FRANCISCO — Results from the phase 2 STRIVE trial show that the novel echinocandin rezafungin — formally known as CD101 — demonstrated comparable safety and efficacy to caspofungin for the treatment of invasive Candida fungal infections. The drug’s manufacturer, Cidara Therapeutics, said a phase 3 analysis is currently underway.

Study researcher George R. Thompson, MD, associate professor of medicine at the University of California, Davis, and an Infectious Disease News Editorial Board member, said in an interview that the pharmacokinetics of this echinocandin are novel, with a once-weekly dosing strategy that could be a huge benefit to patients with Candida.

“For a significant number of our patients with Candida glabrata, this could be a medication that they could receive before they go home, and they would essentially be done with therapy,” he said. “This could potentially get patients out of the hospital sooner.”

In STRIVE, patients aged 18 years or older with mycologically confirmed candidemia or invasive candidiasis, or both, were randomly assigned to receive IV rezafungin for up to 4 weeks dosed at either 400 mg weekly (Group 1; n = 33) or 400 mg on the first week and then 200 mg weekly thereafter (Group 2; n = 31), or standard care, which consisted of daily IV caspofungin with optional oral stepdown therapy after at least 3 days (Group 3; n = 28).

Thompson and colleagues tracked the number of treatment-emergent adverse events (TEAEs) across the three groups, and they defined overall success as a composite endpoint of clinical cure plus mycological success.

The researchers said there was a high number of indeterminate responses in Group 1 because of missing data points, so they conducted two analyses — one that included the indeterminate responses and one that excluded them. Thompson explained that the reason for the number of indeterminate responses was “a lack of comprehensive follow up” in the phase 2 trial. Healthy patients are often harder to follow up with, and those who did not show up were counted as treatment failures.

“This won’t be an issue in the phase 3 trial,” he added.

The researchers said they found no concerning safety trends. Study findings showed that the rate of TEAEs was 88.6% in Group 1, 94.4% in Group 2 and 81.8% in Group 3. Severe adverse events occurred in 37.1%, 27.8% and 39.4% of the groups, respectively.

The most common Candida species that was isolated was C. albicans (n = 45), followed by C. glabrata (n = 17), C. tropicalis (n = 15) and C. parapsilosis (n = 13).

Treatment efficacy was similar across all three groups. According to the researchers, the rate of overall success at day 5 was highest in Group 2 (67.7%), followed by Group 1 (57.6% with indeterminate responses and 65.5% without them) and Group 3 (53.6%).

At day 14, the rate of overall success was again highest in Group 2 (71%), followed by Group 3 (64.3%) and Group 1 (57.6% with indeterminant responses and 73.1% without them).

The overall mortality rate was 15.2% in Group 1, 9.7% in Group 2 and 17.9% in Group 3, the researchers said.

The researchers acknowledged the small sample size and that the findings will need to be confirmed, but they said the results support further clinical study of rezafungin.

Thompson mentioned that rezafungin will be studied in children as well. He also said that in addition to treating invasive fungal infections — which are a challenge in the ICU setting — the drug can be used as prophylaxis, particularly in the bone marrow transplant population.

With the emergence of fluconazole-resistant Candida species over the past decade or more, Thompson said rezafungin will be an important addition to the armamentarium.

“The unique pharmacokinetics parameters of rezafungin really has the potential for improved efficacy,” he said. “There’s a very low side-effect profile, just like other agents in the class. So, I think there’s a big advantage overall, and it should be a big step forward.” – by John Schoen

Reference:

Thompson GR, et al. Abstract 1718. Presented at: IDWeek; Oct. 3-7, 2018; San Francisco.

Disclosures: Thompson is an investigator for and reports receiving research support from Cidara. He also reports ties with Astellas, Mayne, Scynexis and Vical. Please see the abstract for all other authors’ relevant financial disclosures.

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