Background: Ixekizumab, an interleukin-17A (IL-17A) inhibitor used in psoriasis treatment, has been linked to drug-induced interstitial lung disease (DI-ILD). The pathophysiological mechanisms and histopathological features of this adverse effect remain poorly documented.Case Presentation: A 69-year-old male with familial psoriasis developed respiratory symptoms after 18 months of ixekizumab therapy. His medical history included mild smoking-related interstitial pneumonia and chronic obstructive pulmonary disease. One month after treatment, he presented with cough and dyspnea. High-resolution chest CT showed bilateral ground-glass opacities, accompanied by elevated Krebs von den Lungen-6 and surfactant protein-D levels. Transbronchial lung cryobiopsy (TBLC) revealed a fibrotic non-specific interstitial pneumonia pattern with granulomatous changes. Immunohistochemical analysis demonstrated a predominance of CD4-positive cells and IL-17A-positive lymphocytes, suggesting Th17 cell involvement in the pathogenesis. The patient's condition improved following ixekizumab discontinuation.Conclusions: This case identifies distinct histopathological features in ixekizumab-induced DI-ILD, particularly the presence of granulomatous changes and Th17 cell involvement. The findings suggest that IL-17A inhibition may trigger pulmonary inflammation through Th17 cell function dysregulation. This observation supports the importance of careful pulmonary monitoring in patients receiving biologic therapies for psoriasis, particularly those with pre-existing lung conditions. TBLC may contribute to understanding the pathogenesis of this drug-induced complication.

2024-12-01·ANNALS OF THE RHEUMATIC DISEASES

Low uveitis rates in patients with axial spondyloarthritis treated with bimekizumab: pooled results from phase 2b/3 trials

Article

作者: Rudwaleit, Martin ; van Gaalen, Floris A ; Deodhar, Atul ; Brown, Matthew A ; Marten, Alexander ; White, Katy ; Fleurinck, Carmen ; Haroon, Nigil ; Massow, Ute ; Gensler, Lianne S ; van der Horst-Bruinsma, Irene ; de Peyrecave, Natasha ; Vaux, Thomas

Objectives:

Acute anterior uveitis (‘uveitis’) is a common axial spondyloarthritis (axSpA) extramusculoskeletal manifestation. Interleukin (IL)-17 is implicated in its pathogenesis, however, there is conflicting evidence for IL-17A inhibition in uveitis management. We report pooled analyses of uveitis incidence in patients receiving bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, from phase 2b/3 trials.

Methods:

Data were pooled for patients receiving BKZ 160 mg or placebo in the double-blind treatment period of the phase 3 BE MOBILE 1 (NCT03928704; non-radiographic axSpA) and BE MOBILE 2 (NCT03928743; radiographic axSpA) trials. Data were separately pooled for patients treated with at least one BKZ dose in the BE MOBILE trials and their ongoing open-label extension (OLE;NCT04436640), and the phase 2b BE AGILE trial (NCT02963506; radiographic axSpA) and its ongoing OLE (NCT03355573). Uveitis rates and exposure-adjusted incidence rates (EAIR)/100 patient-years (PYs) are reported.

Results:

In the BE MOBILE 1 and 2 double-blind treatment period, 0.6% (2/349) of patients receiving BKZ experienced uveitis vs 4.6% (11/237) receiving placebo (nominal p=0.001; EAIR (95% CI): 1.8/100 PYs (0.2 to 6.7) vs 15.4/100 PYs (95% CI 7.7 to 27.5)). In patients with history of uveitis, EAIR was lower in patients receiving BKZ (6.2/100 PYs (95% CI 0.2 to 34.8); 1.9%) vs placebo (70.4/100 PYs (95% CI 32.2 to 133.7); 20.0%; nominal p=0.004). In the phase 2b/3 pool (N=848; BKZ exposure: 2034.4 PYs), EAIR remained low (1.2/100 PYs (95% CI 0.8 to 1.8)).

Conclusions:

Bimekizumab, a dual-IL-17A/F inhibitor, may confer protective effects for uveitis in patients with axSpA.

2024-12-01·Medical Mycology Case Reports

Challenging case of tinea corporis and faciei in psoriatic patient treated with bimekizumab: The usefulness of mycological screening before biological therapies

Article

作者: Campione, Elena ; Borselli, Cristiana ; Artosi, Fabio ; Gaziano, Roberta ; Shumak, Ruslana Gaeta ; Cosio, Terenzio

Psoriasis is a multifactorial immune-mediated disorder linked to the interleukin (IL)-17 signalling pathway. We present an unusual case of tinea corporis and faciei caused by Trichophyton tonsurans that developed after starting the IL-17A/F inhibitor bimekizumab. Our case underlines how psoriatic patients, treated with IL-17 inhibitors, should be screened for cutaneous fungal infections before and during treatment, in order to exclude a concomitant infection or the risk of its exacerbation.

项与 IL-17A抑制剂 (C4XD) 相关的新闻（医药）

2024-08-27

·PMLiVE

Acelyrin shares positive phase 3 results for izokibep in hidradenitis suppurativa

Acelyrin has shared positive results from a late-stage study of its IL-17A inhibitor izokibep in hidradenitis suppurativa (HS), but has said it will not be moving forward with the asset in this indication. Estimated to affect about 1% of the population in most studied countries, HS is a chronic inflammatory skin condition that causes painful nodules and abscesses. In the phase 3 trial, izokibep demonstrated statistically significant responses across multiple efficacy endpoints at week 12, with 33% of patients being treated with izokibep 160mg weekly achieving at least a 75% reduction in total abscess and inflammatory nodule count (HiSCR75) compared to 21% of those receiving placebo. Results also showed that 25% and 22% of izokibep-treated patients achieved HiSCR90 and HiSCR100, respectively, compared to 9% and 8% in the placebo cohort. The announcement comes shortly after the drug demonstrated promising results in a phase 2b/3 study for psoriatic arthritis (PsA), a chronic inflammatory disease characterised by joint pain, stiffness and swelling. Acelyrin said it will complete the ongoing HS and PsA trials, but will suspend new investment in these indications. A phase 2b/3 trial of izokibep in uveitis will also continue through its primary endpoint, with top-line data expected later this year. Mina Kim, Acelyrin’s chief executive officer, said: “While [this] positive HS data and previously announced PsA data supports a path to approval for izokibep, we have determined that a programme of this breadth and size is best brought to market by a larger organisation with the resources and existing footprint in these indications.” The company outlined that it will now be prioritising the development of lonigutamab, an anti-IGF-1R monoclonal antibody being evaluated as a treatment for thyroid eye disease (TED). A phase 2 dose-ranging study of the candidate is ongoing and Acelyrin hopes to initiate a phase 3 trial of the drug early next year. “We remain excited by the opportunity for lonigutamab to address unmet needs of patients with TED. Consistent with our commitment to disciplined capital allocation, we have decided to focus our eﬀorts toward rapidly advancing lonigutamab through late-stage development with our existing cash resources,” Kim said.

临床3期临床2期临床结果

2024-08-24

·佰傲谷BioValley

一场甩锅CRO的闹剧后

在2023年的纳斯达克交易市场上，一家名为Acelyrin的初创公司的IPO备受瞩目，赚足了投资者们的目光，以5.4亿美元融资金额，创下近两年来生物技术初创公司募资规模最大的一次IPO。上市当日，Acelyrin股价大涨30.56%，市值达到21亿美元，Acelyrin股价峰值最高达29.8美元/股。无论是从发行价、发行规模，还是首日涨幅，都足以体现资本市场对其热情之高。然而，从风光上市到陷入困境，Acelyrin仅花了不到一年时间。如同其他Biotech公司一样，Acelyrin在过去的一年多时间中经历了临床失败，高管辞职，和战略重组。如今，公司的股价已经跌至不足5美元，总市值仅为4.75亿美元。风光无限的IPO Acelyrin成立2020年，是一家以License in为主要经营模式的Biotech公司。 Acelyrin在引进方面有一个较为突出的优点，就是聚焦。虽然凭借与被安进278亿美元收购Horizon公司相同的创始团队背景，Acelyrin在一级市场就已获得投资人青睐，但Acelyrin并没有在融到钱后大肆的买进管线，而是始终把重心押注在Izokibep这一条管线上。也是依靠这一条管线，支撑公司成功走到了IPO。 Izokibep是一种IL-17A抑制剂，是Acelyrin于2021年11月以2500万美元首付款+3亿美元里程碑付款从Affibody收购获得。 Izokibep的分子量仅为单抗的十分之一，可以通过皮下注射，达到传统单抗静脉给药的吸收水平。同时Izokibep还拥有不输于单抗的半衰期，在皮肤、关节等组织器官领域有着独特治疗优势。 Acelyrin也围绕银屑病关节炎 (PsA) 、化脓性汗腺炎（HS）、葡萄膜炎、中轴型脊柱关节炎 (AxSpA)多个适应症进行了临床开发。与CRO间的相互甩锅然而上市几个月后，这条支柱管线就遭遇临床挫折。2023年9月11日，宣布Izokibep治疗化脓性汗腺炎的Ⅱb/Ⅲ期临床未达到主要终点HiSCR。作为Acelyrin的核心支柱管线，化脓性汗腺炎又是其开发的关键适应症，这一临床失败消息立即引发了市场的剧烈反应，Acelyrin股价暴跌62%。 Acelyrin自然不愿轻易接受这个结果，根据公司当时对失败原因的推测，Acelyrin认为临床终点未达到可能是受到停药的影响，也可能是源自临床试验设计缺陷。总之，Acelyrin对izokibep的治疗潜力持乐观态度。顺着这一推测，Acelyrin很快找到了为该临床失败的买单方--其合作的CRO公司Fortrea。2023年11月27日，Acelyrin公告发文表示，Fortrea在Izokibep进行银屑病关节炎（PsA）临床试验时犯了“临床方案执行错误”，导致公司遭受损失。尽管Acelyrin没有直指这项失败的临床试验，但公司的里话外都暗示有可能CRO的临床执行失误导致的，因为该项临床也是由该CRO公司负责推进的。而Fortrea认为Acelyrin在甩锅，这家在向美国证券交易委员会提交的一份文件中表示，对Acelyrin发布的关于izokibep两项临床试验声明准确性提出了质疑。尽管甩锅事件至今并没有定论，但无疑对Acelyrin和Fortrea来说都是双输局面，两家公司合作关系因此彻底崩裂，Acelyrin表示以后不会再与Fortrea合作，而Acelyrin也并没有因此挽救它的股价，反而该事件公布后又下跌了30% 。被下调优先级虽然Izokibep遭遇临床失败，但远远还没有到希望彻底破灭的程度，并且在今年3月，Izokibep在化脓性汗腺炎在长期随访和治疗银屑病关节炎两个适应症解取得了积极的数据。但甩锅事件似乎招致了投资人对公司的信任问题，这则公告也似乎暗示了Izokibep在银屑病关节炎中取得的数据并不乐观，而且也让投资者对Acelyrin的执行力产生了怀疑。今年5月，创始人兼首席执行官Shao-Lee Lin已经辞职，由其首席法律和行政官Mina Kim接任CEO职位。而新CEO上任后也采取了重组措施，将裁员33%，调整管线优先级，以将现金跑道延长至2027年中期。这个重组方案还是令大跌眼镜，这款支撑一路走来的核心管线竟然被下调优先级，不再是公司最首要、最优先的管线。根据重组方案，其收购而来的Lonigutamab被列为管线最高优先级，未来将集中精力推进该管线的临床开发，而至于Izokibep，公司将暂停对Izokibep在屑病关节炎和化脓性汗腺炎两个适应症上任何新的资金投入，同时，另一条管线SLRN-517也被移出。 SLRN-517和Lonigutamab均为公司在2023年年初收购ValenzaBio公司而来的管线，Lonigutamab是一种靶向IGF-1R单抗，在甲状腺眼病中进行临床Ⅰ期试验。SLRN-517是一种靶向c-KIT的全人源IgG1单克隆抗体，用于治疗慢性荨麻疹，还未进入临床阶段。参考出处 https://firstwordpharma.com/story/5885299 https://www.globenewswire.com/Tracker?data=dhmrDtQKPFF1IhgI0S2yTK772QTWGDGRI1FcQfHCWgDBN56HAgvrzH9Ve3eeuqDsGep0d2t9WDXciMoxG5qTwTEJJiqaqY3V843UX8KUOwk6G099PVajJLa5T0J1WpcTAf1VdXy_w-xRe3JLRk0LdWo-N31TRZWrX-InpgjFJ8Y= 本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

并购IPO

2024-08-14

·Pharma Manufacturing

Startup Acelyrin shifts pipeline, lays off staff

Despite a positive phase 3 trial for its lead candidate, izokibep, California biotech Acelyrin revealed plans to cease investments in the IL-17A inhibitor, instead focusing on its thyroid eye disease (TED) candidate. The "refocused pipeline strategy" will use the company's existing cash resources to prioritize lonigutamab, a mid-stage subcutaneous anti-IGF-1R treatment. Acelyrin is currently testing diﬀerent doses and dose regimens with a goal of establishing a minimum eﬀective dose and selecting the dose regimen for the phase 3 program, which the biotech anticipates starting in the ﬁrst quarter of 2025. The strategic shift will also come with a 33% workforce reduction, which the company anticipates will extend its cash runway to mid-2027 and fully fund both phase 3 trials for lonigutamab. In the same press release, Acelyrin revealed that its phase 3 trial of izokibep in chronic skin disease, hidradenitis suppurativa (HS), had achieved its primary endpoint of HiSCR75 (75% reduction in total abscess and inflammatory nodules) at 12 weeks. While the company plans to complete the drug's ongoing trials in HS and active psoriatic arthritis, going forward, it will suspend new investment in the indications. “While today’s positive HS data and previously announced psoriatic arthritis (PsA) data support a path to approval for izokibep, we have determined that a program of this breadth and size is best brought to market by a larger organization with the resources and existing footprint in these indications,” said Mina Kim, Acelyrin CEO. Acelyrin was one of the biggest biotech IPOs of 2023, raising $540 million in May 2023.

临床3期IPO临床结果

100 项与 IL-17A抑制剂 (C4XD) 相关的药物交易

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