09:28am Thursday 20 February 2020

A better way to treat deadly Aspergillus mold infection

(SACRAMENTO, Calif.) — Researchers at UC Davis and other institutions have shown that isavuconazole, a new treatment for invasive mold diseases such as Aspergillus, has fewer side effects than voriconazole and is just as effective. These results are good news for leukemia and lymphoma patients, who can be vulnerable to these opportunistic infections. The study  was published Dec. 9 in The Lancet.

George Thompson George Thompson

“Molds are ubiquitous in the environment, but they are generally no consequence for people with intact immune systems,” said George R. Thompson, associate professor of medicine at UC Davis and a lead author on the paper. “However, for leukemia and lymphoma patients, and others with compromised immune systems, some molds can be 90 percent fatal. The drugs we’ve used for years can be very toxic to the kidney and liver. We’ve needed new therapies with similar efficacy and fewer side effects.”

These results show isavuconazole may be the new treatment physicians have been looking for. In the phase III, double-blind trial, 516 patients were treated with either isavuconazole or voriconazole, the current mainline treatment for invasive mold disease. Patients in both groups had similar response rates: 35 percent for isavuconazole and 36.4 percent for voriconazole.

However, patients in the isavuconazole group had significantly fewer adverse reactions to the drug: 42.4 percent against 59.8 percent for voriconazole. Isavuconazole also had fewer interactions with other drugs. These findings are likely to change how invasive mold disease is treated.

“With 17 percent fewer side effects, isavuconazole is probably going to become the first line treatment of choice for aspergillus,” said Thompson.

For blood cancers patients, mold disease presents a terrible choice. If left untreated, these infections can be quite deadly. However, if chemotherapy is suspended to focus on the mold infection, patients may succumb to their cancer.

“When these patients get a bad infection, they still need more chemotherapy,” said Thompson. “It’s one thing to cure the infection but they end up dying of leukemia. Now that there’s a drug with fewer side effects, patients can hopefully continue their chemotherapy with fewer interruptions.”

Thompson and colleagues have contributed to isavuconazole research for nearly a decade. The team started working with the compound more than nine years ago, proving its efficacy against molds in test tubes. Further studies led to this and other phase III trials.

There is even more good news for patients. Isavuconazole (under the trade name Cresemba) has been approved by the Food and Drug Administration to treat invasive aspergillosis and mucormycosis.

“We’re really hopeful that, for patients who already have a rough time with chemotherapy, isavuconazole will give them an easier road,” said Thompson.

Other authors included: Johan A. Maertens, Issam Raad, Kieren A. Marr, Thomas F. Patterson, Dimitrios P. Kontoyianni, Oliver A. Cornely, Eric J. Bow, Galia Rahav, Dionysios Neofytos, Mickael Aoun, John W. Baddley, Michael Giladi, Werner J. Heinz, Raoul Herbrecht, William Hope, Meinolf Karthaus, Dong-Gun Lee, Olivier Lortholary, Vicki A. Morrison, Ilana Oren, Dominik Selleslag, Shmuel Shoham, Misun Lee, Rochelle Mahe, Anne-Hortense Schmitt-Hofmann, Bernhardt Zeiher, Andrew J. Ullmann.

Isavuconazole has been developed by Astellas and Basilea Pharmaceutica International.

The research study is entitled “Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial.”

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