Lilly Reports One-year Histologic Outcomes in Phase 3 Study of Mirikizumab Compared to Ustekinumab for Crohn's Disease
Lilly Reports One-year Histologic Outcomes in Phase 3 Study of Mirikizumab Compared to Ustekinumab for Crohn's Disease
Data show more patients treated with mirikizumab achieved histologic response at Week 52 compared to ustekinumab
數據顯示,與烏斯特金單抗相比,更多接受米利基珠單抗治療的患者在第52周達到組織學反應
New data are first-of-its-kind analysis of microscopic mucosal resolution that go beyond endoscopy, setting a new potential standard for the evaluation of therapeutic response
新數據是關於微觀黏膜癒合的首次分析,超越內窺鏡檢查,爲治療反應的評估設定了新的潛在標準
INDIANAPOLIS, Oct. 14, 2024 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) announced data demonstrating more patients with moderately to severely active Crohn's disease treated with mirikizumab achieved histologic response at Week 52 compared to ustekinumab, regardless of prior biologic experience. VIVID-1 is the first Phase 3 study for any approved or investigational treatment in Crohn's disease to report histologic and combined histologic-endoscopic outcomes that were evaluated using a systematic assessment of five bowel segments (four colonic and one ileal) and strict definitions consistent with the recently published European Crohn's and Colitis (ECCO) position statement on mucosal histopathology. These results are being presented as an oral presentation at United European Gastroenterology (UEG) Week, held in Vienna, Austria from October 12-15.
印第安納波利斯,2024年10月14日 / PR Newswire / - 艾禮莉莉與公司(NYSE:LLY)宣佈:相比烏斯特金單抗,更多中重度活動克羅恩病患者在第52周接受米利基珠單抗治療達到組織學反應,無論之前有無生物製劑經驗。 《VIVID-1》是首個針對任何經批准或研究的克羅恩病治療進行的第3期研究,報告了組織學和組合組織學-內窺鏡結局,這些結局使用對五個腸段(四個結腸和一個迴腸)進行系統評估的嚴格定義,並符合最近發表的歐洲克羅恩病和結腸炎學會(ECCO)有關粘膜組織病理學的立場聲明。 這些結果將在於10月12日至15日期間在奧地利維也納舉辦的歐洲消化病協會(UEG)週會議上以口頭報告的方式展示。
Mirikizumab is an IL23p19 antagonist that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. Inflammation due to the overactivation of the IL-23 pathway plays a critical role in pathogenesis of Crohn's disease, a chronic, inflammatory bowel disease associated with progressive bowel damage, disability and decreased health-related quality of life.
Mirikizumab是IL23p19拮抗劑,選擇性地結合IL-23的p19亞基並抑制其與IL-23受體的相互作用。由於IL-23途徑過度活化引起的炎症在克羅恩病的發病機制中起着關鍵作用,克羅恩病是一種伴隨進行性腸道損傷、殘疾和健康相關生活質量下降的慢性炎症性腸病。
Crohn's disease inflammation occurs at the cellular level—defined as histologic inflammation—and persists even after treatment with standard of care therapies in up to one-quarter of patients with Crohn's disease despite evidence of endoscopic mucosal healing.1
克羅恩病炎症發生在細胞水平 - 被定義爲組織炎症 - 並且即使經過標準治療仍在高達四分之一的克羅恩病患者中持續存在,儘管有內窺鏡黏膜癒合的證據。
"Treatment strategies for Crohn's disease must evolve beyond traditional measures of clinical remission and endoscopy, to the evaluation of depth of intestinal healing by measuring histologic and transmural resolution," said Fernando Magro, M.D., Ph.D., head of clinical pharmacology at University Hospital São João. "These histologic data build on the growing body of evidence for mirikizumab, which may provide a greater depth of mucosal healing for those living with this chronic, progressive disease."
「克羅恩病的治療策略必須超越傳統的臨床緩解和內窺鏡措施,評估腸道癒合深度,通過測量組織學和經肌壁分辨率來衡量」,聖若昂大學醫院的臨床藥理學負責人費爾南多·馬格羅博士說。 「這些組織學數據爲米利基珠單抗提供了更多的黏膜癒合深度,可能爲那些患有這種慢性進行性疾病的患者提供更大的幫助。」
In VIVID-1, mirikizumab achieved nominally statistically significant improvements across all histologic and histologic-endoscopic endpoints versus placebo at Weeks 12 and 52, and versus ustekinumab on the following endpoints. A greater number of patients that achieved histologic response were observed with mirikizumab at Week 52 in the overall population (58.2% versus 48.8%; p=0.0075). In patients with active histologic disease at baseline and with at least one prior biologic failure, mirikizumab also showed greater histologic response at Week 52 (56.5% versus 41.3%; p=0.0064) and endoscopic-histologic response at Week 52 (39.6% versus 27.8%; p=0.024).
在VIVID-1中,mirikizumab在第12周和第52周的各項組織學和組織學-內鏡學終點與安慰劑相比達到了名義上具有統計學意義的改善,並與烏斯特金單抗在以下終點上相比也有所改善。與安慰劑相比,在總體人群中mirikizumab在第52周觀察到了更多達到組織學反應的患者(58.2%對48.8%; p=0.0075)。在基線處於活躍組織學疾病狀態且至少已經失敗一種生物藥的患者中,mirikizumab在第52周也展示了更好的組織學反應(56.5%對41.3%; p=0.0064)和第52周的內鏡-組織學反應(39.6%對27.8%; p=0.024)。
The overall safety profile of mirikizumab in patients with moderately to severely active Crohn's disease was consistent with the known safety profile in patients with ulcerative colitis (UC). The frequency of serious adverse events was greater in placebo than mirikizumab. The most common adverse events were COVID-19, anemia, arthralgia, headache, upper respiratory tract infection, nasopharyngitis and injection site reactions.
mirikizumab在患有中重度活躍克羅恩病的患者中的整體安全概況與潰瘍性結腸炎(UC)患者的已知安全概況一致。嚴重不良事件的發生頻率在安慰劑組中高於mirikizumab。最常見的不良事件包括COVID-19、貧血、關節痛、頭痛、上呼吸道感染、鼻咽炎和注射部位反應。
"As the first company to report rigorous histologic and endo-histologic outcomes in Crohn's disease that align with a recent ECCO position statement, Lilly is setting a higher bar for the evaluation of long-term treatment response in inflammatory bowel disease. This includes more ambitious targets of mucosal healing, which we applied to compare mirikizumab's histo-endoscopic effect to ustekinumab," said Mark Genovese, M.D., senior vice president of Lilly Immunology development. "These data also broaden our understanding of the underlying inflammation that drives Crohn's disease and may represent a critical step forward in helping health care providers and their patients make more informed choices about treatment."
「作爲第一家報告與最近ECCO立場聲明一致的嚴格克羅恩病組織學和組織學-內鏡學結果的公司,Lilly正在設定更高的標準,用於評估炎症性腸病的長期治療反應。這包括更雄心勃勃的黏膜癒合目標,我們將其用於比較mirikizumab的組織-內鏡效果與烏斯特金單抗,」Lilly免疫學發展高級副總裁Mark Genovese 萬.D.表示。「這些數據還擴展了我們對導致克羅恩病的潛在炎症的理解,可能代表了向前邁出的關鍵步驟,有助於醫護提供者及其患者就治療做出更明智的選擇。」
Lilly has submitted marketing authorization applications for mirikizumab in Crohn's disease around the globe, including in the U.S., Europe, Japan and China. Additional global regulatory submissions are planned.
Lilly已在全球範圍內向各地提交了mirikizumab用於克羅恩病的上市授權申請,包括美國、歐洲、日本和中國。計劃提交其他全球監管申請。
Lilly is committed to finding solutions to elevate care and improve treatment outcomes for people living with inflammatory bowel disease, which includes studying the long-term efficacy and safety of mirikizumab in pediatric patients (NCT05509777 and NCT04844606) and adults (NCT04232553).
Lilly致力於尋找方案,以提高炎症性腸病患者的護理水平並改善治療效果,其中包括研究兒童患者(NCT05509777和NCT04844606)和成人(NCT04232553)使用米里基單抗的長期療效和安全性。
Mirikizumab is approved for the treatment of moderately to severely active UC in adults and is marketed as Omvoh. Mirikizumab has additional ongoing trials in UC, including a study in pediatric patients (NCT05784246) and a study to evaluate the long-term efficacy and safety of mirikizumab in adults (NCT03519945). Lilly is continuing to advance the science with an open-label UC trial studying two new endpoints in the assessment of bowel urgency with frequency and deferral time, both of which impact the quality of life for patients (NCT05767021).
米里基單抗已獲批用於治療成人中至重度活動性UC,並以Omvoh品牌銷售。米里基單抗還在UC領域進行持續試驗,包括在兒童患者中進行研究(NCT05784246)以及評估成人患者使用米里基單抗的長期療效和安全性的研究(NCT03519945)。Lilly正在繼續推動科學,進行開放標籤的UC試驗,研究兩個新的終點,評估腸道急迫感和排便時間,這兩者都會影響患者的生活質量(NCT05767021)。
About the VIVID-1 Clinical Trial Program
有關VIVID-1臨床試驗項目
VIVID-1 was a Phase 3, randomized, double-blind, treat-through study that evaluated the safety and efficacy of mirikizumab compared with placebo and an active control (ustekinumab) in adults with moderately to severely active Crohn's disease. Patients randomized to mirikizumab were administered 900 mg of mirikizumab intravenously every four weeks from Week 0-12, then 300 mg subcutaneously every four weeks from Weeks 12-52. In this study, 49% of patients taking mirikizumab or placebo had experienced a prior biologic failure.
VIVID-1是一項3期、隨機、雙盲、繼續治療研究,評估了與安慰劑和活性對照(烏司替金曲)相比,米里基單抗在中至重度活動性克羅恩病患者中的安全性和有效性。接受米里基單抗治療的患者從第0-12周每四周靜脈滴注900毫克,然後從第12-52周每四周皮下注射300毫克。在這項研究中,將米里基單抗或安慰劑的患者中有49%曾經經歷過生物治療失敗。
Indications and Usage for Omvoh (mirikizumab-mrkz) (in the United States)
Omvoh(Mirikizumab-MRKZ)(在美國)的適應症和用法
Omvoh is indicated for the treatment of moderately to severely active ulcerative colitis in adults.
Omvoh適用於成年人中病情中度至嚴重的潰瘍性結腸炎。
Important Safety Information for Omvoh (mirikizumab-mrkz)
Omvoh的重要安全信息(Mirikizumab-MRKZ)
CONTRAINDICATIONS - Omvoh is contraindicated in patients with a history of serious hypersensitivity reaction to mirikizumab-mrkz or any of the excipients.
禁忌症-Omvoh禁用於有Mirikizumab-MRKZ或任何輔料嚴重過敏反應史的患者。
WARNINGS AND PRECAUTIONS
警告及注意事項
Hypersensitivity Reactions
過敏反應
Serious hypersensitivity reactions, including anaphylaxis during intravenous infusion, have been reported with Omvoh administration. Infusion-related hypersensitivity reactions, including mucocutaneous erythema and pruritus, were reported during induction. If a severe hypersensitivity reaction occurs, discontinue Omvoh immediately and initiate appropriate treatment.
使用Omvoh期間已報告過嚴重的超敏反應,包括靜脈注射期間的過敏性休克。在誘導期間報告了與輸液有關的超敏反應,包括粘膜皮膚紅斑和瘙癢。如果出現嚴重的超敏反應,請立即停止使用Omvoh並採取適當的治療。
Infections
感染。
Omvoh may increase the risk of infection. Do not initiate treatment with Omvoh in patients with a clinically important active infection until the infection resolves or is adequately treated. In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing Omvoh. Instruct patients to seek medical advice if signs or symptoms of clinically important acute or chronic infection occur. If a serious infection develops or an infection is not responding to standard therapy, monitor the patient closely and do not administer Omvoh until the infection resolves.
Omvoh可能會增加感染的風險。在臨床重要的感染得到緩解或得到充分治療之前,不要在患有臨床重要活動性感染的患者中開始Omvoh治療。對於患有慢性感染或反覆感染史的患者,在處方Omvoh之前請考慮風險和收益。如果出現重要的急性或慢性感染跡象和症狀,請指示服用者儘早尋求醫療建議。如果出現嚴重的感染或感染無法對標準治療產生反應,請密切監測患者,並在感染得到緩解之前暫時不要使用Omvoh。
Tuberculosis
結核病
Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with Omvoh. Do not administer Omvoh to patients with active TB infection. Initiate treatment of latent TB prior to administering Omvoh. Consider anti-TB therapy prior to initiation of Omvoh in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after Omvoh treatment. In clinical trials, subjects were excluded if they had evidence of active TB, a history of active TB, or were diagnosed with latent TB at screening.
在使用Omvoh治療之前,評估患者是否患有結核病感染。不要在患有活動性肺結核病的患者中使用Omvoh。在注射Mirikizumab-MRKZ之前,先治療潛伏性結核病。在具有慢性結核病或複發性結核病史的患者中,在處方Omvoh之前,請考慮風險和收益。在和之後的Omvoh治療過程中,監測是否存在活動性結核病的跡象和症狀。在臨床試驗中,被排除的主體是有活動性結核病證據,有結核病或在篩查期間被診斷爲潛伏性結核病的患者。
Hepatotoxicity
肝毒性
Drug-induced liver injury in conjunction with pruritus was reported in a clinical trial patient following a longer than recommended induction regimen. Omvoh was discontinued. Liver test abnormalities eventually returned to baseline. Evaluate liver enzymes and bilirubin at baseline and for at least 24 weeks of treatment. Monitor thereafter according to routine patient management. Consider other treatment options in patients with evidence of liver cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction.
在服用時間比推薦的更長的誘導方案之後,一名臨床試驗病患因藥物性肝損傷伴有瘙癢而報告。Omvoh被停止服用。肝臟測試異常最終返回基線。在基線時和至少在治療24周之間評估肝酶和膽紅素。根據例行患者管理繼續監測。在存在肝硬化證據的患者中,請考慮其他治療選擇。建議及時調查肝酶上升的原因,以識別潛在的藥物性肝損傷情況。如懷疑藥物性肝損傷,請停止用藥,並排除此診斷。請指導患者如果出現提示肝功能異常的症狀,立即就醫。
Immunizations
免疫接種
Avoid use of live vaccines in patients treated with Omvoh. Medications that interact with the immune system may increase the risk of infection following administration of live vaccines. Prior to initiating therapy, complete all age-appropriate vaccinations according to current immunization guidelines. No data are available on the response to live or non-live vaccines in patients treated with Omvoh.
在接受Omvoh治療的患者中避免使用活疫苗。 與免疫系統相互作用的藥物可能會增加接種活疫苗後感染風險。 在開始治療之前,根據當前的免疫接種指南完成所有適齡接種。 目前沒有關於接受Omvoh治療的患者對活疫苗或非活疫苗的反應的數據。
ADVERSE REACTIONS
DEVOTE研究數據(高
Most common adverse reactions (≥2%) associated with Omvoh treatment are upper respiratory tract infections and arthralgia during induction, and upper respiratory tract infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection during maintenance.
接受Omvoh治療的最常見不良反應(≥2%)包括誘導過程中的上呼吸道感染和關節痛,維持期間的上呼吸道感染、注射部位反應、關節痛、皮疹、頭痛和單純皰疹病毒感染。
MR HCP ISI UC APP
MR HCP ISI UC APP
Please click for Prescribing Information and Medication Guide for Omvoh. Please click for Instructions for Use included with the device.
請點擊以獲取Omvoh處方信息和藥物指南。請點擊以獲取包含設備使用說明的說明書。
About Omvoh
關於Omvoh
Omvoh (mirikizumab-mrkz) is an interleukin-23p19 antagonist indicated for the treatment of moderately to severely active ulcerative colitis in adults. Omvoh selectively targets the p19 subunit of IL-23 and inhibits the IL-23 pathway. Inflammation due to over-activation of the IL-23 pathway plays a critical role in the pathogenesis of ulcerative colitis. Treatment of ulcerative colitis with Omvoh starts with 300-mg IV infusions, once every four weeks for a total of three infusions, and transitions to two, 100-mg subcutaneous injections every four weeks during maintenance treatment.
Omvoh(mirikizumab-mrkz)是一種針對成人中度至重度活動性潰瘍性結腸炎的白細胞介素-23p19 拮抗劑。Omvoh 選擇性靶向 IL-23 的 p19 亞基,並抑制了 IL-23 通路。由於 IL-23 通路過度活化引起的炎症在潰瘍性結腸炎的發病機制中起着關鍵作用。使用 Omvoh 治療潰瘍性結腸炎的方法爲每四周一次的 300 毫克靜脈輸注,共三次輸注,然後轉爲每四周兩次的 100 毫克皮下注射進行維持治療。
Omvoh and its delivery device base are trademarks owned by Eli Lilly and Company.
Omvoh 及其遞送裝置的基礎是艾默生(Eli Lilly and Company)的商標。
About Lilly
關於艾禮制藥公司 艾禮制藥公司是一家把科學轉化爲醫治,使全球人民生活變好的醫藥公司。
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY
Eli Lilly是一家醫藥公司,將科學轉化爲治療,致力於爲全球人民改善生活。我們已經開創性地進行生命改變性的發現將近150年,如今我們的藥物幫助全球數千萬人。藉助生物技術、化學和基因藥物的力量,我們的科學家正在緊急推進新的發現,以解決世界上一些最重大的健康挑戰:重新定義糖尿病護理;治療肥胖並遏制其最具破壞性的長期影響;推動對抗阿爾茨海默病的鬥爭;爲一些最具破壞性免疫系統紊亂提供解決方案;並將最難治療的癌症轉變爲可管理的疾病。在走向更健康的世界的每一步,我們的動力來源於一件事:讓成千上萬的人生活更美好。這包括開展反映我們世界多樣性的創新臨床試驗,並努力確保我們的藥物具有可及性和負擔性。欲了解更多信息,請訪問Lilly.com和Lilly.com/news,或在Facebook、Instagram和LinkedIn關注我們。P-LLY
Cautionary Statement Regarding Forward-Looking Statements
關於前瞻性聲明的警示聲明
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about mirikizumab as a potential treatment for people with moderately to severely active Crohn's disease and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study results to date, or that mirikizumab will receive FDA and other additional regulatory approvals, or that it will be commercially successful. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.
本新聞稿包含有關米里基單抗作爲治療中度至重度克羅恩病患者的潛在療效的前瞻性陳述(如《1995年私人證券訴訟改革法》中所定義)。這反映了Eli Lilly當前的信仰和期望。然而,與任何藥品產品一樣,在藥物研究、開發和商業化過程中存在重大的風險和不確定性。除其他事項外,無法保證計劃中或正在進行的研究將如計劃完成,未來的研究結果是否與迄今的研究結果一致,或者米里基單抗將獲得FDA和其他額外的監管批准,或者它將在商業上取得成功。有關這些以及其他可能導致實際結果與Eli Lilly期望不符的風險和不確定性的進一步討論,請參閱Eli Lilly向美國證券交易委員會提交的10-k和10-Q表格。除法律要求外,Eli Lilly沒有義務更新前瞻性陳述以反映本公告日期之後的事件。
1Molander P, Sipponen T, Kemppainen H, et al. Achievement of deep remission during scheduled maintenance therapy with TNFa-blocking agents in IBD. J Crohn's Colitis 2013;7:730–735.
1 Molander P,Sipponen t,Kemppainen H,等人。TNFa阻斷劑在炎症性腸病預定維持治療期間達到深度緩解。J Crohn's Colitis 2013;7:730–735。
Lilly USA, LLC 2024. All rights reserved.
Lilly USA,LLC 2024年。保留所有權利。
Refer to: |
Cathy Buck; [email protected]; +1-317-982-1153; (Lilly media) |
Joe Fletcher; [email protected];+1-317-296-2884; (Lilly investors) |
參見: |
Cathy Buck;[email protected];+1-317-982-1153;(Lilly媒體) |
Joe Fletcher;[email protected];+1-317-296-2884;(Lilly投資者) |
SOURCE Eli Lilly and Company
出處Eli Lilly and Company