麻豆传媒

An investigational treatment for acromegaly -- also known as gigantism -- was safe and boosted biochemical control, according to final topline findings of the phase III .

Meeting the primary endpoint of the 52-week, long-term safety and extension study, once-monthly octreotide subcutaneous depot (CAM2029) was well-tolerated and had a safety profile comparable to standard-of-care treatment with first-generation somatostatin receptor ligands (extended-release octreotide and lanreotide), said developer Camurus in a press release.

The most common adverse events (AEs) were mild to moderate injection-site reactions and gastrointestinal events. There were no severe AEs related to the treatment. One patient had a treatment-related serious AE of moderate cholelithiasis that resolved, and the patient continued treatment in the trial. Two patients discontinued treatment due to AEs -- mild depression in one case and mild injection-site hemorrhage in the other.

Acromegaly is a rare, slowly progressive disease, usually caused by a pituitary gland tumor that is producing excess growth hormone and stimulating increased insulin growth factor-1 (IGF-1) levels, which results in abnormal growth of bone and tissue, as well as enlarged hands, feet, facial features, and inner organs. Symptoms include fatigue, joint pain, headache, visual field defects, excessive sweating, and paresthesia.

"The results from ACROINNOVA 2 are very encouraging and demonstrated that CAM2029 octreotide SC [subcutaneous] depot was effective in normalizing IGF-1 levels across patient groups and continuously improving symptoms of acromegaly throughout the 52 weeks of treatment," study investigator Joanna Spencer-Segal, MD, PhD, of the University of Michigan in Ann Arbor, said in a statement.

Compared with standard-of-care treatment at baseline, the octreotide subcutaneous depot significantly increased IGF-1 response rate -- defined as mean IGF-1 levels ≤1 × upper limit of normal (ULN) -- by 12.7% (95% CI 5.5-19.9) in the overall population.

There was also an increase of 22.8% (95% CI 11.6-33.9) in treatment response rate compared with standard of care at baseline among new patients who didn't roll over from the prior trial. Rollover patients who already had IGF-1 control with standard-of-care treatment at baseline were able to maintain biochemical control with the monthly injectable.

Octreotide subcutaneous depot also led to continuous improvement of acromegaly symptom scores and patient-reported outcomes, such as treatment satisfaction, quality of life, and self-injection assessment scores, compared with standard-of-care treatment.

These results build upon that Camurus released last year, based on adults with acromegaly already on stable treatment with one of the current standard-of-care treatment options. First-line treatment is then followed by other therapies if there is an inadequate response, which varies greatly among this patient population.

While long-acting injectable octreotide is already available, CAM2029 is the first formulation in a prefilled autoinjector pen. "CAM2029 has demonstrated an approximate five-fold higher bioavailability compared to the currently approved, long-acting, intramuscular octreotide," Camurus noted.

Spencer-Segal added that "the convenience of a once-monthly subcutaneous dosing using the prefilled autoinjector pen contributed to improved treatment satisfaction and quality of life, which are important unmet needs for patients living with acromegaly."

The open-label study included 135 patients with acromegaly: 81 new patients directly enrolled in the trial who were either biochemically controlled or uncontrolled at screening (IGF-1 <2 × ULN) and 54 patients who had rolled over from the 24-week ACROINNOVA 1 study. These patients were biochemically controlled at screening (IGF-1 ≤1 × ULN).

In ACROINNOVA 1, octreotide subcutaneous depot was superior to placebo, with an IGF-1 response rate of 72.2% versus 37.5% (P=0.0018).

In the interim ACROINNOVA 2 findings, the full study population had an 8.7% (95% CI 0.6-16.8) increase in IGF-1 response rate. New rollover patients had an 18.3% (95% CI 6.5-30.1) increase in response rate.

Camurus has the findings to the FDA for approval, with a decision expected in October. Octreotide subcutaneous depot is also under development for gastroenteropancreatic neuroendocrine tumors and polycystic liver disease, the company noted.

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