FDA Orphan Drug Designation to Amplyx Pharmaceuticals for APX001 for Treatment of Cryptococcosis

Amplyx Pharmaceuticals, a company developing first-in-class products for life-threatening infections, announced  that the U.S. Food and Drug Administration (FDA) Office of Orphan Product Development has granted orphan drug designation to APX001, the company’s lead drug candidate, for treatment of cryptococcosis.

Orphan drug designation qualifies APX001 for seven years of market exclusivity in the U.S. upon FDA approval of a new drug application (NDA) for the orphan designated indications. APX001 had previously received orphan drug designation for the treatment of invasive candidiasis, invasive aspergillosis, coccidioidomycosis, and rare mold infections caused by Scedosporium spp., Fusarium spp., and Mucorales fungi (including Mucor spp., and Rhizopus spp.). In addition to orphan designations, FDA had previously granted Qualified Infectious Disease Product (QIDP) designation for APX001 for treatment of cryptococcosis, invasive candidiasis, invasive aspergillosis, and coccidioidomycosis. QIDP provides significant development incentives including eligibility for Fast Track designation, priority review and when combined with orphan drug designation, a total of twelve years of marketing exclusivity.

“Orphan and QIDP designations highlight the potential for APX001 to address unmet needs of patients with rare, life-threatening infections,” said Ciara Kennedy, Ph.D., President and Chief Executive Officer of Amplyx. “And with the FDA’s recent addition of cryptococcal meningitis to its list of neglected tropical diseases, Amplyx has the potential to obtain a valuable Tropical Disease Priority Review Voucher from the FDA, creating additional value for Amplyx and its stakeholders.”

Cryptococcosis is an infectious disease of the lungs or central nervous system (the brain or spinal cord) caused by the fungus Cryptococcus (either Cryptococcus neoformans or Cryptococcus gattii), which is typically found in the environment and inhaled. Brain infections due to the fungus Cryptococcus are called cryptococcal meningitis. Infection is most often seen in people with a weakened immune system, including those who are infected with HIV/AIDS, take high doses of corticosteroid medicines, have had an organ transplant, are receiving immune suppressing therapies for cancer or other diseases, or have Hodgkin’s disease.

“While antiretroviral therapy has successfully extended the lifespan of HIV patients, cryptococcal meningitis remains a leading cause of death in HIV patients, particularly in low and middle-income countries,” said Michael Hodges, MD, Chief Medical Officer of Amplyx. “The standard therapy of intravenous amphotericin B plus flucytosine requires inpatient hospitalization and has been known to cause significant side effects including anemia and kidney toxicity. APX001, Amplyx’s first-in-class antifungal agent, in combination with fluconazole, has the potential to be a transformational life-saving, once daily, all oral treatment for cryptococcal meningitis.”

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Fluconazole Use Doesn't Up Risk of Stillbirth, Neonatal Death

In continuation of my update on Fluconazole

Fluconazole use in pregnancy seems not to be associated with significantly increased risks of stillbirth or neonatal death, according to a research letter published in the June 12 issue of the Journal of the American Medical Association.

Björn Pasternak, M.D., Ph.D., from the Karolinska Institutet in Stockholm, and colleagues examined whether fluconazole use during pregnancy is associated with stillbirth and neonatal death. The authors used nationwide register data to identify all pregnancies with singleton live births and stillbirths in Sweden and Norway. A total of 10,669 exposed and 106,690 unexposed pregnancies from a cohort of 1,485,316 pregnancies were included in the matched analysis of stillbirth, and 10,640 exposed and 106,387 unexposed pregnancies were included in the matched analysis of neonatal death.

The researchers found that there were 2.7 and 3.6 stillbirths per 1,000 exposed and unexposed pregnancies, respectively (hazard ratio, 0.76; 95 percent confidence interval, 0.52 to 1.1) and 1.2 and 1.7 neonatal deaths per 1,000 exposed and unexposed pregnancies, respectively (risk ratio, 0.73; 95 percent confidence interval, 0.42 to 1.29). Similar results were seen for doses of 300 mg or less and more than 300 mg.

"Although the data on fluconazole use in pregnancy suggest no increased risk of stillbirth, additional studies should be conducted and the collective body of data scrutinized by drug authorities before recommendations to guide clinical decision making are made, and weighed against the benefits of therapy," the authors write.

The Antidepressant Sertraline Provides a Promising Therapeutic Option for Neurotropic Cryptococcal Infections

New research conducted by biologists at Texas A&M University suggests that sertraline (see structure below, ZOLOFT®), one of the most widely prescribed antidepressants in the world, also packs a potential preventative bonus  potent mechanisms capable of inhibiting deadly fungal infections. 

C. neoformans is a potentially dangerous fungal pathogen found in many soils throughout the world that may cause systemic infections, particularly involving the central nervous system. In most cases, the microscopic, airborne fungal cells of C. neoformans cause asymptomatic colonization in the lungs. However, Lin says the fungus is particularly aggressive in people with weakened immune systems and can spread to other parts of the body, such as the brain and spinal cord, resulting in cryptococcal meningitis  a condition that, in absence of treatment, is fatal.