Mallinckrodt announced data from its phase 4, multicenter, open-label study to assess the efficacy and safety of Acthar Gel (repository corticotropin injection) in adult patients with treatment-resistant, severe noninfectious keratitis, a disease which involves painful inflammation of the cornea.1 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 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.2
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).4
“As ophthalmologists, we rely heavily on patient-reported symptoms when evaluating severe keratitis, especially for those who require alternative treatments,” study author David Wirta, MD, Ophthalmologist, Eye Research Foundation, Newport Beach, said in a company news release. “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 4 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.4
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.4
“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.”
About the Study:4
- The study was designed to evaluate the efficacy and safety of Acthar Gel in adult patients with treatment-resistant, severe non-infectious keratitis.
- In the 16-week study period, 36 patients were enrolled at eight sites across the United States.
- To ensure inclusion of moderate to severe dry eye patients, eligibility criteria included all of the following in at least one eye (the same eye) at screening and baseline:
- Inferior corneal fluorescein staining score of at least two points in any field in at least one eye.
- Sum corneal fluorescein staining score ≥4.
- Sum lissamine green conjunctival score of ≥2.
- Conjunctival redness score ≥1 (0-4 scale).
- Schirmer score ≥1 mm and ≤10 mm/5 min in at least one eye.
- Ocular Discomfort Score of ≥2.
- After a 28-day screening, subjects who met entry criteria were treated with Acthar Gel 1 mL (80 units) subcutaneously twice per week for 12 weeks, followed by a tapering period of four weeks.
- The mean age of the study population was 63.3 years, and most patients were female (71.4 percent), White (80.0 percent) and not of Hispanic or Latino ethnicity (94.3 percent).
Find out more information about the study here on the ClinicalTrials.gov website.
1 Sharma S. Keratitis. Bioscience Reports. 2001;21:419-444.
2 Acthar® Gel (repository corticotropin injection) [prescribing information]. Mallinckrodt ARD LLC.
3 Fairchild CJ, et al. Optom Vis Sci. 2008;85(8):699-707.
4 Grieco J, McLaurin E, Ousler G, Liu J, Kacmaz O, Wirta D. Results from a multicenter, open-label, Phase 4 study of repository corticotropin injection in patients with treatment-resistant severe non-infectious keratitis. Presented at: Association for Research in Vision and Ophthalmology Annual Meeting; May 1, 2021; San Francisco, CA.
5 Collier SA, Gronostaj MP, MacGurn, AK, Cope JR, Awsumb KL, Yoder JS, et al. Estimated burden of keratitis–United States, 2010. MMWR Morb Mortal Wkly Rep. 2014;63(45):1027–1030.
6 Donzis PB, Mondino BJ. Management of noninfectious corneal ulcers. Surv Ophthalmol. 1987;32:94–110.