FDA approves oral therapy for acromegaly
The FDA approved an oral form of the somatostatin analogue octreotide as a long-term maintenance therapy for people with acromegaly who have responded to and tolerated treatment with octreotide injection or lanreotide.
Octreotide (Mycapssa, Chiasma) is the first and only oral somatostatin analogue approved by the FDA and the first product approved by the FDA using Chiasma’s Transient Permeability Enhancer (TPE) technology, according to a press release from Chiasma.
“The FDA approval of Mycapssa represents a major therapeutic advancement for people with acromegaly and validation of our TPE delivery platform,” Raj Kannan, CEO of Chiasma, said in the release. “We are grateful to patients, health care providers, advocates and clinical trial investigators, as well as our employees who have worked diligently to bring Mycapssa to people with acromegaly. As we move into this next exciting phase as a commercial company, we are prepared to execute on a successful U.S. launch by working with healthcare providers to bring Mycapssa to as many patients who could benefit from it.”
In the release, Shlomo Melmed, MB, ChB, MACP, executive vice president of Academic Affairs and dean of the Medical Faculty at Cedars-Sinai, said the approval ushers in a “new era of treatment” for people with acromegaly.
“Over the last 30 years, treating physicians have come to trust octreotide in the treatment of acromegaly, and an oral alternative allows patients to avoid many of the documented treatment burdens associated with injections,” Melmed, also an Endocrine Today Editorial Board Member, said.
As Healio previously reported, adults with acromegaly assigned octreotide maintained a biochemical response at 36 weeks achieved with previous injection therapy with no serious adverse events, according to findings from the OPTIMAL trial.
In the randomized controlled trial, researchers analyzed data from 56 adult patients with active acromegaly, defined as an insulin-like growth factor I level of at least 1.3 times the upper limit of normal at least 3 months after last pituitary surgery, and an average IGF-I level below one times the upper limit of normal while prescribed a stable dose somatostatin receptor ligand injections (octreotide or lanreotide [Somatuline Depot, Ipsen]).
Researchers randomly assigned participants to octreotide (n = 28) or placebo (n = 28) for 36 weeks, followed by an optional, open-label oral octreotide extension phase. Primary endpoint was the proportion of participants maintaining a biochemical response, defined as IGF-I level below one times the upper limit of normal (a two-value average at weeks 34 and 36).
At 36 weeks, 58% of participants assigned octreotide and 19% of participants assigned placebo maintained an IGF-I response (P = .008). Mean IGF-I levels were within the reference range at 36 weeks for participants in the octreotide group (mean, 0.97 times the upper limit of normal) vs. those assigned placebo (mean, 1.69 times the upper limit of normal).
Many adults with acromegaly prescribed long-acting somatostatin receptor ligand injections as first-line therapy report limitations, such as disease symptoms that worsen near the end of the injection cycle, as well as injection site pain, Susan Samson, MD, PhD, FRCPC, FACE, associate professor in the department of endocrinology, diabetes and metabolism at Baylor College of Medicine in Houston and principal investigator of the OPTIMAL clinical trial, told Healio in March.
“The approval of oral octreotide capsules provides an exciting new treatment option for our patients with acromegaly, many of whom are currently burdened with monthly or daily injections,” Samson, who is also an Endocrine Today Editorial Board Member, said. “For our patients, this oral therapy can provide liberty from the pain of injections and the disruption of their family and work lives, while harnessing a familiar and effective treatment for acromegaly. We understand the clinical benefits of octreotide very well: How it works, its potential for IGF-1 and tumor control, and also what to expect in terms of side effects. I am thrilled that we will now have the opportunity to provide octreotide to our patients with acromegaly as a novel oral therapy.”
The company expects octreotide to be commercially available in the fourth quarter of 2020 subject to FDA’s timely approval of a planned manufacturing supplement to the approved new drug application, according to the release.
Adverse events with octreotide could include cholelithiasis and complications of cholelithiasis; hyperglycemia and hypoglycemia; thyroid function abnormalities; cardiac function abnormalities; and decreased vitamin B12 levels and abnormal Schilling’s tests, according to the release.