Mallinckrodt plc has announced data from its Phase 4, multi-center, open-label study to assess the efficacy and safety of Acthar® Gel (repository corticotropin injection) in adult patients with treatment-resistant, severe non-infectious keratitis, a disease which involves painful inflammation of the cornea. The full results were presented in a poster at The Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, and further data will be shared at the upcoming virtual International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Annual Meeting. The poster can be accessed here on the company's website.
Acthar Gel is approved by the U.S. Food and Drug Administration (FDA) for the treatment of severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as: keratitis, iritis, iridocyclitis, diffuse posterior uveitis and choroiditis, optic neuritis, chorioretinitis, anterior segment inflammation. Please see Important Safety Information for Acthar Gel below.
The primary efficacy endpoint of the study was the proportion of patients who improved by 12 points or more in the symptom bother module of the Impact of Dry Eye on Everyday Life (IDEEL) score at week 12. The IDEEL is a patient-reported outcome assessment with three modules—impact on daily life, treatment satisfaction and symptom bother—and six dimensions. After 12 weeks of treatment with Acthar Gel, 50.0 percent (n=17) of patients experienced improvements in their symptom bother score by at least 12 points, a clinically important change3 (95% CI 33.2, 66.8).
"As ophthalmologists, we rely heavily on patient-reported symptoms when evaluating severe keratitis, especially for those who require alternative treatments," said one of the study authors David Wirta, M.D., Ophthalmologist, Eye Research Foundation, Newport Beach. "The clinically important improvement in the symptom bother module is very encouraging and helps us better understand the potential impact for Acthar Gel to effectively treat appropriate patients with severe keratitis who are in need of additional treatment options."
Exploratory endpoints included the change from baseline to week 12 in each item of the Visual Analog Scale (VAS), and corneal fluorescein staining and conjunctival lissamine green staining as measured by Ora Calibra™ scales. After 12 weeks of treatment with Acthar Gel, all symptoms assessed by the VAS had improved from baseline, with the most pronounced improvements observed for eye dryness and discomfort. Additionally, improvements from baseline in corneal fluorescein staining and conjunctival lissamine green staining were observed as early as week four and were sustained through week 12. Additionally, the proportions of patients who experienced greater than or equal to 20, 30 or 50 percent improvement in the IDEEL symptom bother score at week 12 were 50.0 percent (95% CI 33.2, 66.8), 44.1 percent (95% CI 27.4, 60.8) and 14.7 percent (95% CI 2.8, 26.6), respectively.
Safety was assessed regarding treatment-emergent adverse events (TEAEs) and serious TEAEs collected throughout the study. Of patients in the safety population (n=36), 33.3 percent experienced ≥1 TEAE after initiation of Acthar Gel treatment; most TEAEs were single incidences. In the study, the most commonly reported TEAE was hypertension (n=2). No serious TEAEs were related to the study drug.
"These data provide meaningful evidence to support Acthar Gel's potential role in improving outcomes for patients with severe keratitis that persists after the use of one or more standard treatments," said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer at Mallinckrodt. "We are pleased to be able to share these important data broadly with the healthcare community with the hopes of helping physicians better understand which individuals may benefit from the drug as a treatment alternative."