Aeterna Zentaris Inc., an oncology and endocrinology drug development company, has recruited first patient for a phase IIA trial with its ghrelin agonist, AEZS-130 in patients with cancer cachexia. The study is conducted under a Cooperative Research and Development Agreement (CRADA) between Aeterna Zentaris and the Michael E DeBakey Veterans Affairs Medical Center which is funding the study.
Cachexia, characterized by diminished appetite and food intake in cancer patients, is defined as an involuntary weight loss of at least five per cent of the pre illness body weight over the previous six months. Jose M Garcia, MD, PhD, Assistant Professor, Division of Diabetes Endocrinology and Metabolism, Departments of Medicine, Molecular and Cell Biology, the NCI-designated Dan L Duncan Cancer Centre and the Huffington Centre on Aging at Baylor College of Medicine and Michael E DeBakey Veterans Affairs Medical Centre, is acting as the principal investigator of this trial conducted in Houston, Texas.
AEZS-130, a ghrelin agonist, is a novel orally-active small molecule that stimulates the secretion of growth hormone by binding to the ghrelin receptor (GHSR-1a). It can be used in both oncology and endocrinology indications. In oncology, the compound is in a phase II A trial in cancer induced cachexia. Since ghrelin agonists such as AEZS-130 have been shown to stimulate food intake and increase body weight in rats and mice, AEZS-130 could lead to better quality of life for patients with cancer-induced cachexia.
Juergen Engel, PhD, president and CEO of Aeterna Zentaris stated, "This is a key study as it allows us to venture into the field of cancer-cachexia, an indication with high unmet medical needs. Because cachexia is very common among cancer patients, our oral ghrelin agonist, AEZS-130, could represent a novel treatment option for many of the 1.5 million people diagnosed with cancer each year, in the US alone.”
This is a double-blind, randomized, placebo-controlled phase II A trial to test the effects of different doses of AEZS-130 in 18 to 26 patients with cancer-cachexia. AEZS-130 will be provided by Aeterna Zentaris. The study will involve three sequential groups receiving differing doses of AEZS-130. Each dose group will have six patients who will receive AEZS-130 and 2 4 patients who will receive placebo. After analysis of safety and efficacy at each dose level vs. placebo, a decision will be taken either to decrease or increase the dose. For this study, adequate efficacy will be defined as a 0.8 kg of body weight gain or a 50 ng/mL increase in plasma IGF-1 levels. The primary objective of the study is to evaluate the safety and efficacy of repeated oral administration of AEZS-130 at different doses daily for one week in view of developing a treatment for cachexia. The following parameters will be recorded to assess efficacy during the study: change of body weight, change of IGF-1 plasma levels, and change of quality of life score (Anderson Symptom Assessment Scale, FACIT-F). Other secondary objectives will include food intake, and changes in the following: appetite, muscle strength, energy expenditure, reward from food and functional brain connectivity.
Over 1,500,000 new diagnoses of cancer are made in the US every year. In most cases, this condition can have a significant impact on the individuals' survival and quality of life. Cachexia, a complex metabolic syndrome associated with underlying illness, is common in patients with cancer. These patients have diminished appetite, food intake and insulin sensitivity all of which contribute to a decrease in functional performance, take a heavy toll on patients' quality of life and are associated with poor survival.
Despite the significant burden that cachexia and other cancer-related symptoms such as anorexia and poor functional status represent to cancer patients, these symptoms often remain undiagnosed and untreated. Moreover, there are currently no approved treatments for cancer-related cachexia.
In endocrinology, final phase III results for AEZS-130 have been disclosed for use as a simple oral diagnostic test for adult growth hormone deficiency (AGHD). AEZS-130 works by stimulating a patient's growth hormone secretion, which normally only occurs during sleep, after which a healthcare provider will measure how well the body responds to that stimulation based on the patient's growth hormone levels over a period of time. Low growth hormone levels, despite giving an effective stimulating agent, confirm a diagnosis of AGHD. AEZS-130 has been granted orphan-drug designation by the FDA for use as a diagnostic test for growth hormone deficiency. Aeterna Zentaris owns the worldwide rights to AEZS-130 which, if approved, would become the first orally-administered diagnostic test for AGHD.