Commentary by: Shlomo Melmed, MD
Commentary by: Jill Sisco, President of the Acromegaly Community
An investigational oral form of octreotide was safe and effective for the treatment of acromegaly, a rare hormonal disorder, in a recent study. The findings suggest that people who respond well to oral octreotide would be able to avoid the burden of injections if the oral form is approved by the U.S. Food and Drug Administration.
Based on the result of this trial, the drug’s developer Chiasma, Inc. plans to submit a New Drug Application to the U.S Food and Drug Administration (FDA) in 2015.
“For those patients who would prefer not to have the injection, this is an option which is oral, safe, and effective,” said lead author of the study Shlomo Melmed, MD, Senior Vice President and Dean, Cedars-Sinai Medical Center, Los Angeles. “These new results using a daily oral drug are an important advance for people with acromegaly,” Dr. Melmed said.
Octreotide is in a class of medication called somatostatin analogs, which currently are only available for use as injections. The injections usually are given once a month. However, towards the end of the monthly cycle, some patients report a wearing-off effect with the emergence of acromegaly symptoms, including severe headache, joint pain, tissue swelling, and coarsening of features.
“In my opinion, by having an option that provides consistent dosing every day, you won’t have those breakthrough symptoms any more,” said Jill Sisco, President of the Acromegaly Community. “I know people who are on the long-acting octreotide and, at the end of the monthly cycle, have to supplement it with short-acting octreotide injection 3 times a day,” she explained. “I know people who miss work because their [breakthrough] headaches are so bad,” she said.
At 13 Months, 62% of Patients Were Well Controlled on Oral Octreotide
The phase 3 trial was designed to see whether people with acromegaly were able to maintain a good response to treatment when switched from their injectable medications to oral octreotide. The study involved 155 people with acromegaly, 89% of whom were well controlled on their regular injectable medications before entering the study. Despite being considered well controlled using laboratory measures, 81% of participants still had acromegaly symptoms while taking injectable medication.
Initially, each patient was given gradually larger doses until the treatment was effective. After 7 months of treatment at a fixed dose, 65% of participants were considered well controlled on oral octreotide. In addition, 86% who completed the fixed-dose phase chose to participate in a voluntary 6-month extension phase in which they continued using oral octreotide. In the extension phase, 62% of people were considered well controlled.
Notably, 85% of the patients who were well controlled on oral octreotide in the first phase of the study maintained this response up to 13 months in the extension phase. For people who responded to oral octreotide, the severity and frequency of acromegaly symptoms improved, compared to when patients took injectable medications.
“That is a very important reassuring message for patients,” Dr. Melmed said. “Once patients know that they are going to be controlled on the drug, the chances are pretty good that they will sustain control over the long term,” Dr. Melmed said.
“If there is an option that delivers medication at a consistent dose and that can improve symptoms even more than with injectable agents, I think that we as patients we should have that option,” Ms. Sisco said. “Being someone who has gone through a clinical trial, I know that you don’t go on to an extension trial unless a medication is working better than your previous treatment,” Ms. Sisco said. “That is what gives me the most hope,” she added.
“Oral octreotide may not work for me, but it may help 10 other people,” Ms Sisco said. “When you are dealing with a rare disease, it is about those people whom it does help,” she noted.
Side Effects of Oral Octreotide Were Similar to Injectable Octreotide
Approximately, 89% of patients experienced an adverse event, the majority (92%) of which were mild to moderate. The most common adverse events reported with oral octreotide in this study were gastrointestinal, neurological, and musculoskeletal. These side effects are similar to those for injectable octreotide or are consistent with symptoms of acromegaly. Most of the side effects, including gastrointestinal symptoms, went away within the first 2 months of treatment.
Melmed S, Popovic V, Bidlingmaier M, et al. Safety and efficacy of oral octreotide in acromegaly: results of a multicenter phase III trial. J Clin Endocrinol Metab. 2015 Feb 9:jc20144113. [Epub ahead of print]