The U.S. Food and Drug Administration (FDA) approved a new treatment for invasive aspergillosis and invasive mucormycosis, two types of severe and life-threatening fungal infections, after review studies conducted at the UT Medicine San Antonio. The drug Cresemba (isavuconazonium sulfate) was accepted in part due to the efforts of the school’s specialist in infectious disease, Dr. Thomas Patterson.
Cresemba represents a new hope for patients affected by these life-threatening fungal conditions, which particularly affect people who have compromised immune systems. Dr. Patterson was responsible for the studies, designing the clinical trials and participating in the data review committee that assessed patient enrollment.
“It is extremely gratifying to have been a part of the CRESEMBA clinical trials since inception, knowing patients and their physicians will now have this option,” said Patterson in a press release.
The triazole antifungal agent Cresemba is a prodrug (a medication that remains inactive until metabolized by the body in order to improve absorption and decrease side effects) that includes the active antifungal agent isavuconazole. It works by provoking several chemical reactions and stopping fungi from producing ergosterol, a crucial constituent of fungi cell membranes.
By blocking the production of ergosterol, the drug is expected to cause the disruption of the cell membrane and a consequent leak and death of the fungi. The effectiveness and safety of Cresemba, which is being co-developed by Astellas Pharma Inc. and Basilea Pharmaceutica International Ltd., was evaluated in two phase 3 clinical trials conducted with adult patients who suffer from the invasive fungal infections.
The UT Health Science Center San Antonio team collaborated with the SECURE trial, which involved 516 patients through 107 international study sites. The patients were randomly administered the drug over 42 days with either Cresemba or a different kind of triazole anti fungal medication, voriconazole. “From the SECURE trial, we learned that CRESEMBA’s side effects were less severe than voriconazole. We hope that patients will be able to tolerate CRESEMBA better long term,” said Patterson.
The findings revealed that 81.4% of patients who received Cresemba survived, in contrast with only 79.8% of patients treated with voriconazole. In addition, 59.6% of patients from the second group experienced side effects related to the treatment, compared to only 42.4% of those who received Cresemba.
The investigators also conducted a second clinical trial, the VITAL study, with a subpopulation of 37 adult patients who suffered from either invasive aspergillosis and kidney problems, or invasive fungal disease caused by other rare fungi. The participants were all treated with Cresemba, resulting in a 62% survival rate.
The FDA approval made Cresemba the sixth antimicrobial product available as a qualified infectious disease product (QIDP), a designation provided to compounds able to address severe or life-threatening infections under the Generating Antibiotic Incentives Now Act. Cresemba has already been granted the orphan drug designation by the FDA.
Patterson believes that the approval of “new therapies for these infectious diseases without the QIDP status would have been very difficult due to their rarity and severity.” However, trizole antifungal treatments have a major impact on the decrease of mortality, which enhances the importance of the decision. Despite the fact that the two invasive fungi are present in the environment, they particularly affect patients who already suffer from leukemia, lymphoma, AIDS, organ transplantation, severe burns, diabetes, poor nutrition and long-term steroid use.
“It has been estimated that about 12,000 cases of invasive aspergillosis and less than 1,000 cases of invasive mucormycosis (also known as zygomycosis) occur annually in the United States, but this may be an underestimate due to the difficulty of diagnosing both of these infections,” explained Patterson.
“Most importantly, these infections are often devastating and life threatening,” he added. “For example, some soldiers who fought in Iraq and Afghanistan who have sustained blast injuries have been infected with invasive mucormycosis, which they can die from even after surviving a horrifying blast injury. This is due to limited effectiveness of the previous antifungal drugs used against these pathogens.”