-- Under-powered Phase 2A pilot study of H.P. Acthar Gel in Diabetic Nephropathy patients failed to fully enroll due to trial design challenges; data insufficient to support clinically relevant conclusions --
July 25, 2017
Mallinckrodt plc (NYSE: MNK), a leading global specialty pharmaceutical company, today posted data to the ClinicalTrials.gov website. The data derived from a legacy Phase 2A pilot study designed and begun under previous ownership to explore an additional new indication for H.P. Acthar® Gel (repository corticotropin injection) to treat diabetic nephropathy (DN). The under-powered pilot study did not achieve targeted enrollment levels due to a number of trial design challenges nor did it generate data sufficient to support clinically relevant conclusions. At present Mallinckrodt does not intend to pursue this new indication further.
The Phase 2A pilot study was entitled "A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Adaptive Design Pilot Safety and Efficacy Study of H.P. Acthar Gel (Acthar) in Patients with Diabetic Nephropathy and Proteinuria." Find more information about the trial results here on the ClinicalTrials.gov website.
Over the past two plus years, Mallinckrodt has been systematically completing all legacy studies that had been initiated by the previous owner of H.P. Acthar Gel and which were ongoing at the time of the acquisition. Several of those studies, including this Phase 2A pilot evaluating a potential new indication for H.P Acthar Gel in treatment of DN patients, were small, underpowered trials.
Steven Romano, M.D., Chief Scientific Officer and Executive Vice President at Mallinckrodt, said, "Given the design challenges associated with this particular study, we knew it had a low probability of providing definitive answers to challenging clinical questions, but we were committed to finishing out the work that was begun. Since acquiring H.P. Acthar Gel in 2014, we have initiated six well-designed, company-sponsored clinical studies, targeting combined enrollment of more than 1,100 patients. We believe these Mallinckrodt-sponsored studies have a higher probability of generating clinically meaningful data."
Romano continued, "In many conditions, the efficacy of medicines in treating different symptoms or features of the disease varies based on the underlying cause. Just as one antibiotic may be effective for controlling fever associated with a specific bacterial infection, but not for another, a treatment effective in management of proteinuria associated with one illness may not be effective in another. The pathophysiology of DN has features distinct from other idiopathic causes of proteinuria, and is a very challenging condition that many drug developers have struggled to address."
"Although a previous independent pilot study (Tumlin et al, 2013) demonstrated a potential benefit from Acthar in some patients with DN, and this Mallinckrodt pilot study suggested a dose-related attenuation in the decline of eGFR at week 36, the company's study failed to demonstrate a statistically significant improvement for the reasons and limitations mentioned," Romano concluded.
Importantly, no new safety issues were identified in this study and, notably, control of diabetes (as measured by HbA1c) did not differ between the H.P. Acthar Gel and placebo groups. As noted previously, Mallinckrodt does not intend to pursue this indication further.
About H.P. Acthar® Gel (repository corticotropin injection)
H.P. Acthar Gel is an injectable drug approved by the FDA for the treatment of 19 indications. Of these, today the majority of H.P. Acthar Gel use is in these indications:
Important Safety Information
Warnings and Precautions
Please see full Prescribing Information here for additional Important Safety Information.
Mallinckrodt is a global business that develops, manufactures, markets and distributes specialty pharmaceutical products and therapies. Areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, nephrology, pulmonology and ophthalmology; immunotherapy and neonatal respiratory critical care therapies; and analgesics and hemostasis products. The company's core strengths include the acquisition and management of highly regulated raw materials and specialized chemistry, formulation and manufacturing capabilities. The company's Specialty Brands segment includes branded medicines and its Specialty Generics segment includes specialty generic drugs, active pharmaceutical ingredients and external manufacturing. To learn more about Mallinckrodt, visit www.mallinckrodt.com.
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Coleman N. Lannum, CFA
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 Tumlin JA, Galphin CM, Rovin BH. Advanced diabetic nephropathy with nephrotic range proteinuria: A pilot study of the long-term efficacy of subcutaneous ACTH gel on proteinuria, 15 progression of CKD, and urinary levels of VEGF and MCP-1. J Diabetes Res. 2013:489869.
 Estimated glomerular filtration rate – the primary efficacy outcome of the study and a measure of renal function