NEW YORK (Reuters Health) – Many patients with acromegaly may do as well on oral octreotide treatment as they do on injectable somatostatin receptor ligands (iSRLs), an industry-sponsored phase-3 trial suggests.
Oral octreotide is the first oral medication approved by the U.S. Food and Drug Administration (FDA) for acromegaly, said Dr. Maria Fleseriu of Oregon Health & Science University in Portland.
“In the first large international randomized trial on different delivery methods in acromegaly, we assessed the maintenance of biochemical response and symptom control with oral octreotide capsules (OOCs) for patients controlled with injectable somatostatin receptor ligands (iSRLs),” she told Reuters Health by email.
“We found that oral octreotide was not biochemically inferior to iSRLs in the randomized phase,” Dr. Fleseriu added. “In the run-in phase where all participants received both treatments sequentially, several symptoms – including joint pain, extremity swelling, and fatigue – were better controlled. Also, patient-reported outcomes were more improved with oral octreotide treatment than with iSRL treatment.”
As reported in The Lancet Diabetes & Endocrinology, Dr. Fleseriu and her colleagues conducted the open-label study over more than four years at 29 clinical sites in ten countries to evaluate the response to oral octreotide capsules compared with iSRLs (long-acting octreotide or lanreotide autogel) in adults with acromegaly who tolerated and responded to both.
Ninety-two of the 146 patients enrolled in the six-month run-in phase were considered responders to oral octreotide (40 mg per day with optional titration to 60 or 80 mg per day). These participants were randomly assigned to either oral octreotide or iSRLs and were followed for nine months or longer.
Fifty of 55 patients (91%) in the oral octreotide group maintained a biochemical response (IGF-1 concentrations less than 1.3 times the upper limit of normal), compared with 37 (100%) of 37 participants treated with iSRLs.
The difference in results between the octreotide and the iSRL groups did not exceed the study’s prespecified noninferiority criterion of -20%, so oral octreotide was deemed noninferior to iSRLs.
The drugs also had similar safety profiles. Overall, 19 of 55 (35%) participants on oral octreotide and 15 (41%) of 37 participants receiving iSRL had treatment-related adverse events, with gastrointestinal problems the most common problem in both groups.
“Acromegaly is rare, and most patients, due to delayed diagnosis, have larger pituitary tumors. They thus have low cure rates after surgery, and most patients need life-long adjuvant medical therapy,” Dr. Fleseriu explained.
“We now have several FDA-approved drugs, with various mechanisms of actions; however, all but one need to be injected daily or monthly,” she added. “Having more treatment options allows for personalized therapy and improved patient outcomes and satisfaction.”
“Some patients will not respond to oral octreotide when they are switched from iSRL,” Dr. Fleseriu noted. “Thus, it is important to optimize dose titration and assess biochemical control after every change in treatment type.”
“More than 60% of patients elected to continue in the extension study,” she said, “and we look forward to longer-term data on patients continuing on oral medication.”
In an accompanying editorial, Dr. Maya B. Lodish of the University of California, San Francisco, writes, “Many individuals with acromegaly must rely on chronic injections for disease management, therefore an oral alternative has many potential advantages, including ease of administration.”
“The current study does not provide data to compare the up-front efficacy of oral versus iSRLs, but does provide evidence that most patients who are already biochemically controlled on stable doses of iSRLs and on oral octreotide will maintain this response when continued on oral octreotide,” Dr. Lodish adds. “We still lack data on the efficacy of oral octreotide capsules as primary medical therapy in patients who have not yet been on iSRLs, which would be helpful in clinical practice.”
The study was funded by Chiasma, which was recently acquired by Amryt Pharmaceuticals. The company sells oral octreotide under the brand name Mycapssa. Dr. Fleseriu and all but one of her co-authors have financial relationships with the company.
SOURCE: https://bit.ly/3qSZypU and https://bit.ly/34sFkf3 The Lancet Diabetes & Endocrinology, online December 22, 2021.
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