The FDA has granted orphan drug designation to miltefosine (Impavido, Profounda Inc.) for treatment of Acanthamoeba Keratitis (AK).
The approval is based on research showing that topical miltefosine (65 µg/mL, 28 days) cured 85% of cases in a hamster model of AK. Currently, most cornea specialists treat AK with a combination of topical and oral antibiotic, antiviral, antifungal and antiparasitic drugs, though visual outcomes are often poor. There is little consensus on an ideal regimen, and use of multiple agents is associated with corneal toxicity and poor patient adherence.
Miltefosine is already approved as an oral medication for treatment of leishmaniasis in patients aged 12 and older in the United States, Germany, India and Israel, and is listed on the World Health Organization’s List of Essential Medicines.
Leishmaniasis is a potentially fatal disease of the skin, mucous membrane or viscera prevalent in developing countries of Asia, Africa, Southern Europe and Central and Southern America. Like AK, leishmaniasis is caused by infection of a single-celled protozoa. While Acanthamoeba are widespread free-living microorganisms, protozoans of the Leishmania genus are parasites transmitted by bites from sandflies.
Though the exact mechanism remains unknown, miltefosine is known to interfere with the mitochondrial function and membrane integrity of Leishmania by disrupting lipid activity, and appears to have a similar effect against Acanthamoeba.
"We are pleased with the FDA's decision to grant orphan drug designation to miltefosine for the treatment of Acanthamoeba Keratitis," said Todd MacLaughlan, CEO of Profounda Inc., "By creating miltefosine-induced alterations to the membrane architecture of the amoeba, miltefosine allows patients a therapeutic option that has potential advantages over conventional therapy approaches."
The drug is also available through the CDC’s emergency access IND protocol for treatment of primary amoebic meningoencephalitis and granulomatous amoebic encephalitis, which are frequently fatal free-living amoeba infections.