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.
Late Breaker口頭報告總結了積極結果，包括成功實現研究的主要和次要終點
數據支持 VK2809 的同類最佳特徵體現在強勁的肝臟脂肪減少、組織學結果顯示 NASH/MASH 消退和纖維化改善以及令人鼓舞的耐受性和安全性
聖地亞哥，2024年11月19日 /PRNewswire/ — 專注於開發代謝和內分泌失調新療法的臨床階段生物製藥公司Viking Therapeutics, Inc.（「Viking」）（納斯達克股票代碼：VKTX）今天宣佈，該公司針對患者進行的新型肝臟選擇性甲狀腺激素受體β激動劑 VK2809 的20年期臨床試驗的最終結果經活檢證實的非酒精性脂肪性肝炎（NASH；也稱爲代謝功能障礙相關的脂肪性肝炎，MASH）在口服晚期中被突出顯示美國肝病研究協會（AASLD）年會2024年第75屆肝臟會議上的精彩演講。該演講總結了VOYAGE研究的最終52週數據，表明VK2809 成功實現了該試驗的主要和次要終點，同時表現出良好的耐受性和良好的安全性。
口頭陳述的要點包括：
52 周時肝臟脂肪含量降低
接受 VK2809 的患者在第 12 周表現出肝脂肪顯著減少，這是 VOYAGE 的主要終點。重要的是，接受 VK2809 的患者在第 52 周繼續表現出肝臟脂肪含量的統計學顯著降低，與基線相比的平均相對變化在 37% 至 55% 之間。該研究的反應率（定義爲肝脂減少≥30％的患者比例）在第52周的64％至88％之間，所有治療組均顯示出與安慰劑相比具有統計學意義的改善。
52 周時的組織學結果
在沒有纖維化惡化的NASH消退的次要終點上，接受VK2809治療的患者的NASH分辨率介於63％至75％之間，而安慰劑的這一比例爲29％（每個 VK2809 治療組的p<0.05）。在合併的 VK2809 治療組中，69% 的治療組達到了 NASH 分辨率（與安慰劑相比 p<0.0001）。NASH 的分辨率定義爲炎症的非酒精性脂肪肝疾病活動分數 (NAS) 爲 0 或 1，膨脹時爲 0。
在評估纖維化改善且不惡化NASH的次要終點上，接受VK2809治療的患者表現出纖維化的改善幅度在44％至57％之間，而安慰劑的這一比例爲34％（5 mg和10 mg QOD隊列的p<0.05）。在 VK2809 聯合治療組中，有 51% 的患者在沒有惡化的 NASH 的情況下實現了纖維化的改善（與安慰劑相比 p=0.03）。在不惡化NASH的情況下改善纖維化被定義爲纖維化的1階段改善，而氣球膨脹、炎症或脂肪變的NAS不增加。
在評估NASH消退和纖維化改善的患者比例的次要終點上，接受VK2809治療的患者表現出從40％到50％不等的改善，而安慰劑的改善幅度爲20％（5 mg和10 mg QOD隊列的p<0.05）。在 VK2809 聯合治療組中，有 44% 達到了這一終點（與安慰劑相比 p=0.003）。如上所述，NASH 的消退和纖維化的改善定義如下。
第 52 周血漿脂質減少
接受 VK2809 的患者表現出安慰劑調整後的低密度脂蛋白（每組 p<0.01）的降低，以及甘油三酯和動脈粥樣硬化蛋白（例如載脂蛋白 b（apoB）、脂蛋白（a）[Lp (a)] 和載脂蛋白 C-III（Apoc-III）的降低，所有這些都與心血管風險相關。這些結果支持先前的數據，這些數據表明，VK2809 可通過大幅降低血漿脂質來提供心臟保護功效。
安全性和耐受性
通過52周的治療，VK2809 在這項研究中顯示出令人鼓舞的安全性和耐受性，與先前報告的12周結果相比差異微乎其微。在接受 VK2809 的患者中，大多數（94%）與治療相關的不良事件被報告爲輕度或中度。由於不良事件導致的停藥率較低，在安慰劑組和治療組之間保持平衡。與先前的研究一樣，在本研究的12周時間點上，VK2809 在本研究的52周治療窗口內表現出良好的胃腸道（GI）耐受性。與安慰劑相比，接受VK2809治療的患者的噁心、腹瀉、大便頻率和嘔吐發生率相似。
加州大學聖地亞哥分校醫學院胃腸病學和肝病學系主任兼MASLD研究中心主任羅希特·盧姆巴萬博士說：「VOYAGE研究的最終52週數據爲VK2809 在NASH/MASH中的治療潛力提供了令人信服的證據。」「肝臟脂肪的顯著減少、令人印象深刻的NASH解決率以及纖維化的改善爲患者提供了一個有吸引力的潛在治療選擇。此外，觀察到的血漿脂質改善表明了潛在的長期心臟保護作用，在這種情況下這是一個寶貴的益處。」
維京首席執行官布萊恩·連博士補充說：「VK2809，加上我們正在進行的肥胖症皮下和口服 VK2735 的臨床活動，以及針對澱粉樣蛋白受體激動劑的臨床前項目，爲維京提供了代謝障礙領域業內最令人興奮和互補的治療產品線之一。我們期待我們在重要代謝疾病方面的研發項目繼續取得進展。」
研究設計
VOYAGE 研究是一項隨機、雙盲、安慰劑對照、多中心的國際試驗，旨在評估 VK2809 對活檢確診的 NASH/MASH 和纖維化患者的療效、安全性和耐受性。入組的患者包括根據MRI-PDFF測得的肝脂含量至少爲8％的患者，以及F2和F3纖維化的患者。該研究允許多達25％的入組患者患有F1纖維化，前提是他們還具有至少一個額外的危險因素，例如糖尿病、肥胖或高血壓等。該研究的主要終點評估了接受 VK2809 治療的患者與接受安慰劑的患者相比從基線到第 12 周肝脂肪含量的變化。次要目標包括評估治療52周後通過肝活檢評估的組織學變化。
