Oral Late Breaker Presentation Summarizes Positive Results Including Successful Achievement of Study's Primary and Secondary Endpoints
Data Support VK2809's Best-in-Class Profile Highlighted by Robust Liver Fat Reductions, Histologic Results Demonstrating NASH/MASH Resolution and Fibrosis Improvement, and Promising Tolerability and Safety
SAN DIEGO, Nov. 19, 2024 /PRNewswire/ -- Viking Therapeutics, Inc. ("Viking") (NASDAQ: VKTX), a clinical-stage biopharmaceutical company focused on the development of novel therapies for metabolic and endocrine disorders, today announced that final results from the company's Phase 2b clinical trial of VK2809, the company's novel liver-selective thyroid hormone receptor beta agonist, in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH; also referred to as metabolic dysfunction associated steatohepatitis, MASH) were highlighted in an oral late breaker presentation at the 75th Liver Meeting 2024, the annual meeting of the American Association for the Study of Liver Disease (AASLD). The presentation summarized the final 52-week data from the VOYAGE study, showing that VK2809 successfully achieved the trial's primary and secondary endpoints while demonstrating excellent tolerability and promising safety.
Highlights from the oral presentation included:
Reduction in Liver Fat Content at 52 Weeks
Patients receiving VK2809 demonstrated statistically significant reductions in liver fat at Week 12, which was the primary endpoint in VOYAGE. Importantly, patients receiving VK2809 continued to demonstrate statistically significant reductions in liver fat content at Week 52, with the mean relative change from baseline ranging from 37% to 55%. The response rate in this study, defined as the proportion of patients experiencing reduction in liver fat ≥30%, ranged from 64% to 88% at Week 52, with all treatment arms demonstrating statistically significant improvement compared to placebo.
Histologic Results at 52 Weeks
On the secondary endpoint of NASH resolution with no worsening of fibrosis, VK2809-treated patients demonstrated NASH resolution ranging from 63% to 75%, compared with 29% for placebo (p<0.05 for each VK2809 treatment group). Across the combined VK2809 treatment groups, 69% achieved NASH resolution (p<0.0001 vs. placebo). Resolution of NASH was defined as a non-alcoholic fatty liver disease activity score (NAS) of 0 or 1 for inflammation and 0 for ballooning.
On the secondary endpoint evaluating improvement in fibrosis with no worsening of NASH, VK2809-treated patients demonstrated improvement in fibrosis ranging from 44% to 57%, compared with 34% for placebo (p<0.05 for the 5 mg and 10 mg QOD cohorts). Across the combined VK2809 treatment groups, 51% achieved improvement in fibrosis with no worsening of NASH (p=0.03 vs. placebo). Improvement in fibrosis without worsening of NASH was defined as a ≥1-stage improvement in fibrosis and no increase in NAS for ballooning, inflammation, or steatosis.
On the secondary endpoint evaluating the proportion of patients experiencing both resolution of NASH and improvement in fibrosis, VK2809-treated patients demonstrated improvement ranging from 40% to 50%, compared with 20% for placebo (p<0.05 for the 5 mg and 10 mg QOD cohorts). Across the combined VK2809 treatment groups, 44% achieved this endpoint (p=0.003 vs. placebo). Resolution of NASH and improvement in fibrosis were defined as described above.
Reduction in Plasma Lipids at Week 52
Patients receiving VK2809 demonstrated placebo-adjusted reductions in LDL-C ranging from 20% to 25% (p<0.01 for each arm), as well as reductions in triglycerides and atherogenic proteins such as apolipoprotein B (ApoB), lipoprotein (a) [Lp(a)], and apolipoprotein C-III (ApoC-III), all of which have been correlated with cardiovascular risk. These results support prior data demonstrating that VK2809 may offer a cardioprotective benefit through its robust reduction in plasma lipids.
Safety and Tolerability
VK2809 demonstrated encouraging safety and tolerability in this study through 52 weeks of treatment, with minimal differences compared with the previously reported results at 12 weeks. The majority (94%) of treatment related adverse events among patients receiving VK2809 were reported as mild or moderate. Discontinuations due to adverse events were low and balanced among placebo and treatment arms. As in prior studies, and at the 12-week timepoint in this study, VK2809 demonstrated excellent gastrointestinal (GI) tolerability throughout the 52-week treatment window in this study. Rates of nausea, diarrhea, stool frequency, and vomiting were similar among VK2809-treated patients compared to placebo.
"The final 52-week data from the VOYAGE study provide compelling evidence of the therapeutic potential of VK2809 in NASH/MASH," said Rohit Loomba, M.D., MHSc, Chief of the Division of Gastroenterology and Hepatology and Director of the MASLD Research Center at University of California San Diego School of Medicine. "The potent reductions in liver fat, impressive NASH resolution rates, and improvements in fibrosis suggest an attractive potential treatment option for patients. In addition, the observed improvements in plasma lipids indicate a potential long-term cardioprotective effect, a valuable benefit in this setting."
Brian Lian, Ph.D., chief executive officer of Viking, added, "VK2809, along with our ongoing clinical activities with subcutaneous and oral VK2735 in obesity, as well as our preclinical program targeting amylin receptor agonists, provides Viking with one of the industry's most exciting and complementary therapeutic pipelines in the field of metabolic disorders. We look forward to continued advancement of our pipeline programs in important metabolic disorders."
Study Design
The VOYAGE study was a randomized, double-blind, placebo-controlled, multicenter, international trial designed to assess the efficacy, safety and tolerability of VK2809 in patients with biopsy-confirmed NASH/MASH and fibrosis. Enrollment included patients with at least 8% liver fat content as measured by MRI-PDFF, as well as F2 and F3 fibrosis. The study allowed for up to 25% of enrolled patients to have F1 fibrosis provided they also possessed at least one additional risk factor, such as diabetes, obesity or hypertension, among others. The primary endpoint of the study evaluated the change in liver fat content from baseline to Week 12 in patients treated with VK2809 as compared to patients receiving placebo. Secondary objectives include the evaluation of histologic changes assessed by hepatic biopsy after 52 weeks of treatment.
