Table 3.
Emerging Therapies for Muscle Dysfunction
| Class | Drug | Populations* | Tools | Notable Outcomes | Adjunct Therapy | Adverse Events |
|---|---|---|---|---|---|---|
| Androgens and progesterone | Megestrol (multiple) | COPD, cancer cachexia, HIV/AIDS–related cachexia | DXA | ↑ Weight after 2 wk, confirmed as fat on DXA (77) | No planned nutrition or PR | Similar to placebo; mostly dyspnea |
| Multiple studies complete/ongoing | Spiro | |||||
| 6-MWT | ||||||
| Mahler-Q | ||||||
| CRD-Q | ||||||
| Oxandrolone (multiple) | COPD, Duchenne muscular dystrophy, HIV, cancer cachexia, FTT, chronic infection, surgery | BIA | ↑ Weight, ↑ in LBM at up to 4 mo, nonsignificant ↑ in 6-MWD (73) | No planned nutrition or PR | Edema, ↑ LFTs studies | |
| Multiple studies complete/ongoing | Spiro | |||||
| 6-MWT | ||||||
| Karnofsky | ||||||
| VAS | ||||||
| Enobosarm (SARM) | Cancer cachexia | DXA | ↑ Total LBM, ↓reduction in stair climb time (76) | No planned nutrition or PR | Nausea, anemia, GI disturbances | |
| Multiple studies complete/ongoing | FAACT | |||||
| FACIT-F | ||||||
| SCP | ||||||
| HGS | ||||||
| SCT | ||||||
| Myostatin pathway inhibitors | Landogrozumab (LY2495655) (Lilly) | Pancreatic cancer cachexia, hip arthroplasty, muscle atrophy | DXA | Trend toward change in aLBM at 12 wk; probability of difference between treatment vs. PBO did not meet statistical significance (128) | Vitamin D supplementation for deficiency; no planned nutrition or PR | Injection site irritation; 7 patients developed anti-LY2495655 antibodies (no clinical significance) |
| Multiple completed studies in various populations | TUG | |||||
| SCP | ||||||
| Leg extension | ||||||
| PINTA/AMG 745 (Atara Biotherapeutics/AMGEN) | Prostate cancer cachexia | DXA | ↑ LBM at 29 d, ↔ SPPB, ↔ leg extension (81) | No planned nutrition or PR | Syncope (1 patient), fatigue, diarrhea, injection site bruising; 1 patient developed anti-AMG 745 antibodies (no clinical significance) | |
| Discontinued by manufacturer | CT | |||||
| Leg extension | ||||||
| SPPB | ||||||
| Bimagrumab (BYM338) (Novartis) | COPD, IBM, IIM, sarcopenia, mechanical ventilation | DXA | ↑ TMV vs. placebo at 4, 8, and 24 wk, ↔ 6-MWD at 24 wk (80) | No planned nutrition or PR | Transient, mild, involuntary muscle contractions | |
| Multiple studies ongoing | 6-MWT | |||||
| TMV | ||||||
| Ghrelin receptor agonist | SUN11031 (Daiichi Sankyo) | COPD | DXA | ↓ 6-MWD in low dose vs PBO, ↔ HGS, ↔ SPPB, post hoc analysis of cachexic subjects show statistically significant ↑6-MWD, HGS, SPPB (89) | No planned nutrition or PR | COPD-related symptoms, injection site irritation, headache, weight reduction; MI in 7 subjects (unrelated to drug) |
| Discontinued by manufacturer | 6-MWT | |||||
| Spiro | ||||||
| SPPB | ||||||
| HGS | ||||||
| Anamorelin (Helsinn Therapeutics) | Cancer cachexia | DXA | ↑ TBM, LBM, and aLBM after 12 wk, ↔ HGS, ↔ FACT (91) | No planned nutrition or PR | Uncontrolled diabetes, hyperglycemia, GI disturbances, edema | |
| Studies completed | HGS | |||||
| FACT | ||||||
| Capromorelin (Pfizer) | Sarcopenia (older adults, age 65–84 yr) | 6-MWT | ↑ SCT after 12 mo, ↔ 6-MWD, nonsignificant ↑LBM after 6 mo (88) | Discontinued by manufacturer | Hyperglycemia (↑ HA1c), insulin resistance, glucosuria, ↑ cholesterol | |
| Discontinued by manufacturer | HGS | |||||
| TWS | ||||||
| SCT | ||||||
| DXA | ||||||
| MMSE | ||||||
| SF-36 | ||||||
| PAI | ||||||
| MOS-SS | ||||||
| β-Receptor blocker | Espindolol (MT-102) (PsiOxus) (nonselective β-blocker) | Colorectal and NSCLC cachexia | DXA | ↑ Weight 4 wk (high dose vs. PBO), ↑ HGS, ↑ 6-MWD, SCP, nonsignificant trend toward improved SPPB (high dose vs. PBO) (129) | Multiple studies complete/ongoing | Anemia, cough, dyspnea |
| HGS | ||||||
| Multiple studies complete/ongoing | 6-MWT | |||||
| SCP | ||||||
| SPPB | ||||||
| EQ-5D |
Definition of abbreviations: 6-MWD = 6-minute-walk distance; 6-MWT = 6-minute-walk test; aLBM = appendicular lean body mass; BIA = bioelectric impedance analysis; COPD = chronic obstructive pulmonary disease; CRD = chronic respiratory disease; CT = computed tomography; DXA = dual-energy X-ray absorptiometry; EQ-5D = EuroQol five dimensions questionnaire; FAACT = Functional Assessment of Anorexia/Cachexia Therapy score; FACIT-F = Functional Assessment of Chronic Illness Therapy-Fatigue; FACT = Functional Assessment of Cancer Therapy; FTT = failure to thrive; GI = gastrointestinal; HA1c = hemoglobin A1c; HGS = handgrip strength; IBM = inclusion body myositis; IIM = idiopathic inflammatory myopathy; LBM = lean body mass; LFT = liver function test; MI = myocardial infarction; MMSE = Mini Mental Status Examination; MOS-SS = Medical Outcomes Study-Sleep Scale; NSCLC = non–small-cell lung cancer; PAI = Physical Activity Index; PBO = placebo; PR = pulmonary rehabilitation; Q = questionnaire; SARM = selective androgen receptor modulator; SCP = stair-climbing power; SCT = stair-climbing time; SF-36 = 36-item short form health survey; SPPB = Short Physical Performance Battery; TBM = total body mass; TMV = thigh muscle volume; TUG = timed up-and-go test; TWS = tandem walk speed; VAS = visual analog scale.
Populations in bold were studied in the trial referred to under the “Notable Outcomes” section.