Once-monthly octreotide provides sustained acromegaly control with fewer injections
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Key takeaways:
- Once-monthly subcutaneous octreotide was associated with persistent control of IGF-I and growth hormone levels for adults with acromegaly.
- There were no new or unexpected safety signals.
BOSTON — Adults with acromegaly previously controlled with standard of care experienced similar disease control with once-monthly injectable octreotide at 24 and 52 weeks, with no serious adverse events, data presented at ENDO 2024 show.
There remains an unmet need for convenient therapies for acromegaly, which is characterized by overproduction of growth hormone and insulin-like growth factor I, according to Diego Ferone, MD, PhD, full professor of endocrinology in the department of internal medicine and medical specialties at the University of Genova, Italy. A key treatment goal is long-term biochemical control to minimize the adverse effects of prolonged GH excess .
CAM2029 (Camurus), a novel subcutaneous octreotide depot, is designed for monthly self-administration using a prefilled syringe or pen, which could help reduce treatment burden, Ferone said during a poster presentation.
“We designed this study with this new compound mostly to improve patient adherence,” Ferone told Healio. “Self-administration with a subcutaneous injection is much less painful than an intramuscular injection. What is very intriguing ... is in the phase 2 trial, we saw better control of IGF-I, and even patients who were already controlled improved slightly. However, there was a very small number of patients and we could not draw conclusions. With phase 3, now we are confirming that this approach seems to work better. It is not only related to patient adherence, but maybe this formulation might better deliver the drug to the receptors.”
Switch to monthly injections
In the phase 3 ACROINNOVA 1 trial, participants with acromegaly previously controlled with standard of care, defined as octreotide long-acting repeatable or lanreotide autogel (Somatuline Depot, Ipsen), who received CAM2029 achieved superior IGF-I control vs. placebo. Upon trial completion, the participants could roll over to a 52-week, open-label, long-term safety trial, ACROINNOVA 2.
For the ACROINNOVA 2 study, researchers analyzed data from 64 participants who completed ACROINNOVA 1 (CAM2029: n = 36; placebo: n = 18 ) who received monthly CAM2029 20 mg for 28 weeks. The primary endpoint was occurrence of adverse events; secondary endpoints included the proportion of patients with available assessments who had an IGF-I up to one time the upper limit of normal at weeks 50 and 52, and well-controlled IGF-I and GH levels.
Researchers found that the medication was well tolerated with a safety profile comparable to standard of care treatment; no new safety signals were observed.
Injection site treatment-emergent adverse events occurred in half of participants in the prior CAM2029 and prior placebo groups. Of evaluable patients, 89.3% in the prior CAM2029 and 100% in prior placebo groups had IGF levels up to one time the upper limit of normal at weeks 50 and 52. Additionally, 88.5% and 100%, respectively, had well-controlled IGF-I and GH levels at weeks 50 and 52.
Mean IGF-I levels remained below the upper limit of normal throughout the 52-week study period for the prior CAM2029 group. In the prior placebo group, mean IGF-I increased above one time the upper limit of normal during placebo treatment, returning to below the upper limit of normal after switching to CAM2029 for 28 weeks. All patients previously treated with placebo regained IGF-I control upon switching to CAM2029.
Benefits for newly enrolled patients
In a second analysis from ACROINNOVA 2 study, researchers analyzed interim data for 81 newly enrolled patients who had adequately or inadequately controlled IGF-I levels on a stable dose of octreotide long-acting release for at least 3 months (mean age, 52 years; 59.3% women), as well as enrolled participants who had already received CAM2029 or placebo in the ACROINNOVA 1 study. The newly enrolled participants received CAM2029 once monthly for up to 52 weeks. The primary endpoint was adverse events; secondary endpoints included proportion of participants with an IGF-I level one time the upper limit of normal or less at 50 or 52 weeks, change from baseline in IGF-I level and combined IGF-I and GH level response.
The most common treatment-emergent adverse events were injection-site erythema (n = 22) or swelling (n = 13) and headache (n = 12). The adverse events were mostly mild to moderate; there were no serious treatment-related adverse events.
Researchers found that IGF-I response increased from 14.8% at baseline with standard of care to 33.3% at weeks 50 and 52. Using a linear probability model, the estimated increase in IGF-I response from baseline at week 52 was 21.9% (95% CI, 9.6-34.1). Biochemical control for both IGF-I and GH improved over time, with 30% of patients having a combined IGF-I and GH response at the end of the main part of trial compared with 11.7% at baseline.
Ferone said the findings reinforce the efficacy and safety of CAM2029 for patients with acromegaly, including patients with uncontrolled disease receiving the current standard of care.
“The main message is this improves patient perspective in the approach to treatment,” Ferone told Healio. “There is a quality of life improvement, which is important for patients with a chronic disorder, and this attention to the patient is very important. The formulation also supports the action of the drug.”
Perspective
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A large recent study showed that adherence to acromegaly treatment is clearly not as high as we would want, thus increasing rates of biochemical uncontrol of these patients and reducing comorbidities is paramount.
These large international studies, led by a well-known acromegaly and neuroendocrine expert, Diego Ferone, MD, PhD, investigated a new delivery for therapy with octreotide, a subcutaneous self-administered injection every 28 days. The advantages of self-administration would be immense, eliminating a trip to the clinic every month and increasing both adherence and persistence to treatment. Results are convincing that efficacy is maintained for patients switching from monthly long-acting octreotide intramuscular or deep subcutaneous lanreotide, while also improving patient satisfaction with this new treatment.
While not all the data have been published, the presented data also shows further improvement in patients who were not completely biochemically controlled before switching treatment, which can further enhance outcome improvements. Safety seems to be overall similar with other forms of delivery for injectable somatostatin receptor ligands.
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Ferone D, et al. SAT-078; SAT-079: ENDO annual meeting; June 1-4, 2024; Boston.
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