UT Health Science Center researcher plays major role in FDA approval of drug for aggressive fungal infections
SAN ANTONIO (March 13, 2015) ― Patients with life-threating fungal infections have new hope for survival and less-severe side effects with the U.S. Food and Drug Administration’s approval of a new drug, isavuconazonium sulfate, also called CRESEMBA®.
CRESEMBA was approved March 6 for the treatment of patients with invasive aspergillosis and invasive mucormycosis, both aggressive fungal infections that attack patients with compromised immune systems.
Thomas Patterson, M.D., FACP, FIDSA, an infectious disease specialist at UT Medicine San Antonio, has been involved in the research, working with drug developers to design clinical trials and serving as co-leader of the data review committee that evaluated patients enrolled in the studies. UT Medicine is the clinical practice of the School of Medicine at The University of Texas Health Science Center at San Antonio
“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 Dr. Patterson, who also is a professor, chief of the Division of Infectious Disease and directs the San Antonio Center for Medical Mycology at the UT Health Science Center.
The two invasive fungi are commonly found in the environment, including soil, dust, decomposing plant matter and even in some foods and spices; however, infections are rare. Those at most risk are patients with leukemia, lymphoma, AIDS, organ transplantation, severe burns, diabetes, poor nutrition and long-term steroid use, according to the National Institutes of Health.
“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,” Dr. Patterson explained.
“Most importantly, these infections are often devastating and life threatening,” he said. “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.”
CRESEMBA is a triazole antifungal agent and a prodrug containing the active antifungal agent isavuconazole. A prodrug is a medicine that is inactive until it is metabolized by the body to help it be better absorbed, to reduce side effects or for other medical reasons.
Like other triazole antifungals, CRESEMBA works through a series of chemical reactions to keep the invasive fungi from producing ergosterol, a key component found in fungi cell membranes. When the fungi are unable to produce ergosterol, there is a disruption in the cell membrane causing the cell to leak and eventually die.
CRESEMBA’s effectiveness and safety profile in patients with invasive aspergillosis was based on data from two Phase 3 clinical trials in adults with invasive fungal infections.
The SECURE trial was a clinical study of 516 patients conducted at 107 study sites throughout the U.S. and across the globe. The patients were treated for 42 days. One group received CRESEMBA and the other voriconazole, a different type of triazole antifungal medication. The results showed 81.4 percent of the patients in the CRESEMBA group survived, compared to 79.8 percent in the group receiving voriconazole. Only 42.4 percent of patients in the CRESEMBA group had drug-related side effects compared to 59.6 percent in the voriconazole group.
The second clinical trial was the VITAL study*, which included a subpopulation of 37 adult patients with either invasive aspergillosis and kidney problems, or invasive fungal disease caused by other rare fungi. All the patients received CRESEMBA and 62 percent survived.
CRESEMBA is the sixth approved antimicrobial product designed as a qualified infectious disease product (QIDP.) This status is given to agents meant to treat serious or life-threatening infections under the Generating Antibiotic Incentives Now Act. The FDA also granted CRESEMBA, available in oral and intravenous formulations, orphan drug status.
The effectiveness of CRESEMBA for the treatment of invasive mucormycosis has not been evaluated in concurrent, controlled clinical trials. Dr. Patterson added that “approving new therapies for these infectious diseases without the QIDP status would have been very difficult due to their rarity and severity.”
Dr. Patterson said that overall, triazole antifungal medications have had a major impact on decreasing death rates for patients with fungal infections. “However, side effects from other antifungal medications can be severe, including liver damage as well as other adverse events such as bone and joint pain, neurological symptoms, as well as neuropathy pain. Long-term side effects also include skin rash that, after the medicine is used for several months to years, can lead to skin cancer.
“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,” he said.
Isavuconazonium sulfate, under the brand name CRESEMBA, is being co-developed by Astellas Pharma Inc. and Basilea Pharmaceutica International Ltd.
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* Please note that Astellas Pharma Inc. is calling it VITAL rather than VICAL.