Randomized study of the efficacy and safety of SUN11031 (synthetic human ghrelin) in cachexia associated with chronic obstructive pulmonary disease

Cancer cachexia has two main components: anorexia and metabolic alterations. The main changes associated with the development of this multi-organic syndrome are glucose intolerance, fat depletion and muscle protein hypercatabolism. The aim of this paper is to review the more recent therapeutic approaches designed to counteract the wasting suffered by the cancer patient with cachexia. Among the most promising approaches we can include the use of ghrelin agonists, beta-blockers, beta-adrenergic agonists, androgen receptor agonists and anti-myostatin peptides. The multi-targeted approach seems essential in these treatments, which should include the combination of both nutritional support, drugs and a suitable program of physical exercise, in order to ameliorate both anorexia and the metabolic changes associated with cachexia. In addition, another very important and crucial aspect to be taken into consideration in the design of clinical trials for the treatment of cancer cachexia is to staging cancer patients in relation with the degree of cachexia, in order to start as early as possible this triple approach in the course of the disease, even before the weight loss can be detected.

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“…35 Finally, Asubio Pharmaceuticals is involved in a phase-II clinical trial with synthetic human ghrelin (SUN11031) in COPD patients. 36…”

Section: Drugs Modulating Appetitementioning

confidence: 99%

Therapeutic strategies against cancer cachexia

Argilés¹,

López‐Soriano²,

Stemmler³

et al. 2019

Eur J Transl Myol

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“…Ghrelin stimulates secretion of GH, via growth hormone secretagogue receptor 1a (GHS-R1a), leading to regulation of multiple functions, from food intake to glucose metabolism (86). In humans, ghrelin has been studied in cancer cachexia, sarcopenia of the elderly, chronic heart failure, and COPD (87)(88)(89)(90)(91). In patients with COPD, ghrelin improved LBM and muscle strength but had mixed results on functional outcomes such as the 6-MWD (87,90).…”

Section: Ghrelinmentioning

confidence: 99%

“…In patients with COPD, ghrelin improved LBM and muscle strength but had mixed results on functional outcomes such as the 6-MWD (87,90). SUN11031, another synthetic human ghrelin, was studied by Levinson and Gertner in clinically stable cachexic patients with COPD (89). This study enrolled 192 patients with BMI less than 21 kg/m 2 and FFMI less than 16 kg/m 2 .…”

Section: Ghrelinmentioning

confidence: 99%

“…This study enrolled 192 patients with BMI less than 21 kg/m 2 and FFMI less than 16 kg/m 2 . Results showed that up to 65% of subjects in both treatment groups gained at least 3% of their body weight after 85 days of treatment (89). Another drug, capromorelin, was tested for 1 year in adults older than 65 years of age with evidence of functional decline on the basis of the Short Form-36 Health Survey and HGS (88).…”

Section: Ghrelinmentioning

confidence: 99%

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Deterioration of Limb Muscle Function during Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Abdulai

Jensen

Patel

et al. 2018

Am J Respir Crit Care Med

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Important features of both stable and acute exacerbation of chronic obstructive pulmonary disease (COPD) are skeletal muscle weakness and wasting. Limb muscle dysfunction during an exacerbation has been linked to various adverse outcomes, including prolonged hospitalization, readmission, and mortality. The contributing factors leading to muscle dysfunction are similar to those seen in stable COPD: disuse, nutrition/energy balance, hypercapnia, hypoxemia, electrolyte derangements, inflammation, and drugs (i.e., glucocorticoids). These factors may be the trigger for a downstream cascade of local inflammatory changes, pathway process alterations, and structural degradation. Ultimately, the clinical effects can be wide ranging and include reduced limb muscle strength. Current therapies, such as pulmonary/physical rehabilitation, have limited impact because of low participation rates. Recently, novel drugs have been developed in similar disorders, and learnings from these studies can be used as a foundation to facilitate discovery in patients hospitalized with a COPD exacerbation. Nevertheless, investigators should approach this patient population with knowledge of the limitations of each intervention. In this Concise Clinical Review, we provide an overview of acute muscle dysfunction in patients hospitalized with acute exacerbation of COPD and a strategic approach to drug development in this setting.

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“…2 Based on these activities, ghrelin has been developed as a potential drug candidate for the treatment of anorexia nervosa 3 and chronic obstructive pulmonary disease cachexia. 4 Furthermore, several small-molecule ghrelinR agonists are in development as potential drug candidates for the treatment of cancer-related anorexia and cachexia syndrome. 5 Conversely, ghrelinR blockage could ameliorate diabetes and obesity, and many ghrelinR antagonists have also been reported by pharmaceutical companies and academic researchers.…”

mentioning

confidence: 99%