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11 200,001-400,000 13 3,340,849 1.75

12 400,001-600,000 11 5,288,967 2.78

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ASLAN00 4-6 ¶g 3¤H,EASI ¥­§¡­°´T¬ù71%(2019/1203¼Æ¾Ú)

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2¡BASLAN004 ±µ¦X IL-13 R£\1«á,

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(signal transducer and activator of transcription 6, pSTAT6)

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1.ASLAN004 MOA -¼v¤ù

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2.Dupilumab MOA -¼v¤ù

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p.7 ¤½¥q³ÌªñªºÂ²¤¶ 20205/26 ³Ì­«­n

1.¾÷Âà(MOA) ¤wÀòµý¹ê: »PdupilumabÂê©w¬Û¦Pªº¸ô®|»P ¨üÅé½Æ¦XÅé(TYPE II RECEPTER «¬II¨üÅé)

2019/05/31 ³o­Ó´N­È20»õ¬ü¤¸ªº§é²{­È, CSL¤Î¨È·à¦U¤À¤@¥b¡A¦U±o10»õ¬ü¤¸¼ç­È

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2. Dupilumab ¥«³õ°Ï¹j : ¨ãÀø®Ä¼W¶i¤§¼ç¤O¡B´î¤Ö¤£¨}¤ÏÀ³(µ²½¤ª¢) ¡B¨C¤ëµ¹ÃĤ@¦¸

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ASLAN004

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MERCK (Àq§J¶°¹Î)/ASLAN004

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3.Dupilumab ·À10%~14%ªº·¥­P ¥­§¡Àø®Ä­°´T¤W¥«¡C(¨C¶g¤@°w vs ¨C¶g¤G°wÀø®Ä®t²§)

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2.¥´°wÀW²v

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2. Dupilumab ¥D­nÀø®Ä«ü¼ÐIGA 0/1 °ª1.33~2­¿ ©ó¨ä¥L ¥u¯à§í¨îIL-13¡Ï³¡¤ÀIL-4/ ³æ§í¨îIL-13 ªº Lebrikiumab/Tarlokinumab

3.Dupilumab ·À10%~14%ªº·¥­P ¥­§¡Àø®Ä­°´T¤W¥«¡C(¨C¶g¤@°w vs ¨C¶g¤G°wÀø®Ä®t²§)

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3.°Æ§@¥Î

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ñ约°ò¦¡A°Ñ¦Ò°ê»Ú¦P级¦X¬ù¡A¦ô³Ì°ª销°â30»õ¬ü¤¸¡C

(·í®ÉDupilumab ¥«³õ»{¦P¥¼¨Ó³Ì°ª¥i销50»õ¬ü¤¸)

2.2020¦~¤¸¤ë Dermira/Lebrikizumab AD ªº¨ÖÁʧé²{»ù­È 29»õ¬ü¤¸.

2020/01 §¨Ó¨ÖÁÊDermira ¤½¥q

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3.2020/7/13

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ASLAN004 AD¥D­nÀø®Ä ±N¦PDupilumab Àu©ó Lebrikiumab/Tarlokinumab 33% ~100%

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2¡BASLAN004 ±µ¦X IL-13 R£\1«á,

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MOA

www.tsim.org.tw/journal/jour29-6/02.PDF?fbclid=IwAR2B85aLqBUAt5agx6K7u0NkCGTGpr7w6HDCagHhLuu54ZH7FEqHMAdXG3M

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Lebrikizumab ¤T´Á,

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Primary Outcome Measures ƒÊ : 1.Percentage of participants with an IGA score of 0 or 1 and a reduction ≥2 points from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

Evaluation of the Efficacy and Safety of Lebrikizumab (LY3650150) in Moderate to Severe Atopic Dermatitis (ADvocate2)

Study Type ƒÊ : Interventional (Clinical Trial)

Estimated Enrollment ƒÊ : 400 participants

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: Randomized, double-blind, parallel group, placebo controlled

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description: Double-blind

Primary Purpose: Treatment

Official Title: A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Lebrikizumab in Patients With Moderate to Severe Atopic Dermatitis.

Actual Study Start Date ƒÊ : November 8, 2019

Estimated Primary Completion Date ƒÊ : June 2021

Estimated Study Completion Date ƒÊ : December 2021

clinicaltrials.gov/ct2/show/NCT04178967?term=Lebrikizumab+PHASE+3&draw=2&rank=10

Primary Outcome Measures ƒÊ : 1.Percentage of participants with an IGA score of 0 or 1 and a reduction ≥2 points from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

Secondary Outcome Measures ƒÊ : 1.Percentage of patients achieving EASI-75 (≥75% reduction in EASI score) from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

2.Percentage of patients achieving EASI-90 (≥90% reduction in EASI score) from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

3.Percentage change in Pruritus Numerical Rating Scale (NRS) score from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

4.Percentage of patients with a Pruritus NRS score of ≥4-points at Baseline who achieve a ≥4-point reduction in Pruritus NRS score from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

5.Percentage of patients with a Pruritus NRS score of ≥5-points at Baseline who achieve a ≥4-point reduction in Pruritus NRS score from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

6.Percentage change in EASI score from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

7.Change from Baseline to Week 16 in percent BSA [ Time Frame: Baseline to Week 16 ]

8.Percentage of patients achieving EASI-90 from Baseline to Week 4 [ Time Frame: Baseline to Week 4 ]

9.Percentage change in Sleep-loss score from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

10.Change from Baseline in Sleep-loss score at Week 16 [ Time Frame: Baseline to Week 16 ]

11.Percentage of patients with a Pruritus NRS score of ≥4 points at Baseline who achieve a ≥4-point reduction from Baseline to Week 1 [ Time Frame: Baseline to Week 1 ]

12.Percentage of patients with a Pruritus NRS score of ≥4 points at Baseline who achieve a ≥4-point reduction from Baseline to Week 2 [ Time Frame: Baseline to Week 2 ]

13.Percentage of patients with a Pruritus NRS score of ≥4 points at Baseline who achieve a ≥4-point reduction from Baseline to Week 4 [ Time Frame: Baseline to Week 4 ]

14.Percentage of patients with a Pruritus NRS score of ≥5 points at Baseline who achieve a ≥4-point reduction from Baseline to Week 1 [ Time Frame: Baseline to Week 1 ]

15.Percentage of patients with a Pruritus NRS score of ≥5 points at Baseline who achieve a ≥4-point reduction from Baseline to Week 2 [ Time Frame: Baseline to Week 2 ]

16.Percentage of patients with a Pruritus NRS score of ≥5 points at Baseline who achieve a ≥4-point reduction from Baseline to Week 4 [ Time Frame: Baseline to Week 4 ]

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Dupilumab treatment in adults with moderate-to-severe atopic dermatitis

Lisa A Beck 1 , Diamant Thaçi, Jennifer D Hamilton, Neil M Graham, Thomas Bieber, Ross Rocklin, Jeffrey E Ming, Haobo Ren, Richard Kao, Eric Simpson, Marius Ardeleanu, Steven P Weinstein, Gianluca Pirozzi, Emma Guttman-Yassky, Mayte Suárez-Fariñas, Melissa D Hager, Neil Stahl, George D Yancopoulos, Allen R Radin

Affiliations Expand

PMID: 25006719

DOI: 10.1056/NEJMoa1314768

Abstract

Background: Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels. The blockade by dupilumab of these key drivers of type 2 helper T-cell (Th2)-mediated inflammation could help in the treatment of related diseases, including atopic dermatitis.

Methods: We performed randomized, double-blind, placebo-controlled trials involving adults who had moderate-to-severe atopic dermatitis despite treatment with topical glucocorticoids and calcineurin inhibitors. Dupilumab was evaluated as monotherapy in two 4-week trials and in one 12-week trial and in combination with topical glucocorticoids in another 4-week study. End points included the Eczema Area and Severity Index (EASI) score, the investigator¡¦s global assessment score, pruritus, safety assessments, serum biomarker levels, and disease transcriptome.

Results: In the 4-week monotherapy studies, dupilumab resulted in rapid and dose-dependent improvements in clinical indexes, biomarker levels, and the transcriptome. The results of the 12-week study of dupilumab monotherapy reproduced and extended the 4-week findings: 85% of patients in the dupilumab group, as compared with 35% of those in the placebo group, had a 50% reduction in the EASI score (EASI-50, with higher scores in the EASI indicating greater severity of eczema) (P<0.001); 40% of patients in the dupilumab group, as compared with 7% in the placebo group, had a score of 0 to 1 (indicating clearing or near-clearing of skin lesions) on the investigator¡¦s global assessment (P<0.001); and pruritus scores decreased (indicating a reduction in itch) by 55.7% in the dupilumab group versus 15.1% in the placebo group (P<0.001). In the combination study, 100% of the patients in the dupilumab group, as compared with 50% of those who received topical glucocorticoids with placebo injection, met the criterion for EASI-50 (P=0.002), despite the fact that patients who received dupilumab plus glucocorticoids used less than half the amount of topical glucocorticoids used by those who received placebo plus the topical medication (P=0.16). Adverse events, such as skin infection, occurred more frequently with placebo; nasopharyngitis and headache were the most frequent adverse events with dupilumab.

Conclusions: Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity. Side-effect profiles were not dose-limiting. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT01259323, NCT01385657, NCT01639040, and NCT01548404.).

pubmed.ncbi.nlm.nih.gov/25006719/

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EASI-50 Dupilumab 71.4%/placebo(¹ï·Ó²Õ)18.8% .¡]1b ,n=21:16 )

Study Type ƒÊ : Interventional (Clinical Trial)

Actual Enrollment ƒÊ : 37 participants

Allocation: Randomized

Intervention Model: Parallel Assignment

Masking: Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose: Treatment

Official Title: A Randomized, Double-Blind, Placebo-Controlled, Sequential Ascending, Repeated-Dose Study of the Safety, Tolerability, and Pharmacokinetics of Subcutaneous REGN668 in Patients With Moderate-to-Severe Atopic Dermatitis

Actual Study Start Date ƒÊ : July 31, 2011

Actual Primary Completion Date ƒÊ : March 31, 2012

Actual Study Completion Date ƒÊ : March 31, 2012

Experimental: Placebo

Placebo (for Dupilumab) as a single subcutaneous (SC) injection on Day 1, 8, 15, and 22

Drug: Placebo

A total of 4 doses were administered.

Other: Background treatment

Participants were required to apply stable doses of an additive-free, basic bland emollient on the affected areas of the skin twice daily throughout the study.

Experimental: Dupilumab 150 mg

Dupilumab 150 mg as a single SC injection on Day 1, 8, 15, and 22

Drug: Dupilumab

A total of 4 doses were administered.

Other Names:•REGN668

•SAR231893

•Dupixent

Other: Background treatment

Participants were required to apply stable doses of an additive-free, basic bland emollient on the affected areas of the skin twice daily throughout the study.

Experimental: Dupilumab 300 mg

Dupilumab 300 mg as a single SC injection on Day 1, 8, 15, and 22

Drug: Dupilumab

A total of 4 doses were administered.

Other Names:•REGN668

•SAR231893

•Dupixent

Other: Background treatment

Participants were required to apply stable doses of an additive-free, basic bland emollient on the affected areas of the skin twice daily throughout the study.

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Significantly greater IGA 0/1 and EASI 75 response rates at week 16 were observed with tralokinumab with and without topical corticosteroids, when compared with placebo. In ECZTRA 1, 15.8% of patients taking tralokinumab had an IGA 0/1, compared with 7.1% on placebo (P = .002), and 25.0% had an EASI 75 versus 12.7% with placebo (P < .001). In ECZTRA 2, the IGA 0/1 proportion was 22.2% versus 10.9% (P < .001), and EASI 75 proportion was 33.2% versus 11.4% (P < .001). For ECZTRA 3, the respective proportions were 38.9% versus 26.2% (P = .015) for IGA 0/1 and 68.0% versus 36.7% (P < .001) for EASI 75.

For the ECZTRA 1 and 2 trials, a sensitivity analysis of nonresponders demonstrated superior outcomes among those on active therapy even in this group. Specifically, the proportion with an IGA 0/1 was 19.1% with active therapy versus 8.1% with placebo (P < .001) in ECZTRA 1 and 24.0% versus 12.4% (P < .001) in ECZTRA 2. For EASI 75, the respective proportions were 33.4% versus 17.3% (P< .01) and 37.9% versus 16.4% (P < .01).

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1 Nutten, S. 2015. Atopic dermatitis: global epidemiology and risk factors

2 Atopic Dermatitis in America, accessed 17 October 2018

3 Decision Resources, 2017

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finance.yahoo.com/news/merck-buy-arqule-2-7b-144202149.html

Merck to Buy ArQule for $2.7B to Boost Cancer Portfolio

Zacks Equity Research

Merck (MRK) offers to acquire ArQule for a deal value of $2.7 billion. The transaction will add ArQule¡¦s lead investigational candidate ARQ 531 to Merck¡¦s oncology portfolio.

December 10, 2019

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• The recommended dose of DUPIXENT for adults and adolescents (12

years of age and older) is:

o an initial dose of 400 mg (two 200 mg injections) followed by 200

mg given every other week or

o an initial dose of 600 mg (two 300 mg injections) followed by 300

mg given every other week

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3539¨Ò¯gª¬¸û»´©ÎÁ{§Éª¬ªp¨}¦n¦ý¤´¹ïCOVID-19´ú¸Õ§e¶§©Êªº¯f¨Ò¤w³Q¹jÂ÷¨Ã¦bªÀ°Ï³]¬I¤¤¶i¦æÅ@²z¡C¡]Ãþ¦ü¤¤°ê¤è¿µÂå°|¡^

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As of 11 July 2020, 12pm, the Ministry of Health (MOH) has confirmed 170 new cases of COVID-19 infection in Singapore.

Among the cases:

Imported case: 1

1 Work Pass holder

There is an imported case today involving an Indian national who returned to Singapore from India on 6 July. She is a Work Pass holder who is currently employed in Singapore. She had been placed on 14-day Stay-Home Notice (SHN) upon arrival in Singapore, and had been tested while serving SHN.

Cases in the community: 24

7 Singaporeans, 6 Work Pass holders, 11 Work Permit holders

Of the 24 cases in the community, 19 were picked up as a result of MOH¡¦s proactive surveillance and screening, and 5 had already been placed on quarantine earlier. 20 of the cases are asymptomatic, and were all detected through our proactive testing. 15 of the community cases are linked to previous cases or clusters, 9 are currently unlinked.

Cases residing in dormitories: 145

Of the new cases, 94% are linked to known clusters, the rest are pending contact tracing.

246 more cases of COVID-19 infection have been discharged from hospitals or community isolation facilities. To date, 42,026 have fully recovered from the infection and have been discharged from hospitals or community isolation facilities.

Most of the 192 confirmed cases who are still in hospital are stable or improving. 1 is in critical condition in the intensive care unit.

3,539 cases who have mild symptoms, or are clinically well but still test positive for COVID-19 are isolated and cared for at community facilities.

26 have passed away from complications due to COVID-19 infection.

www.gov.sg/article/covid-19-cases-in-singapore

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¦P级(¦PMOA)ªºLebrikizumab ¡A¦b250mg /¥|¶g¤@°w¡A¤w¬Û·í©óLE0ªºTralokinumab 300mg/¤G¶g¤@°w¤T´ÁÁ{§Éµ²ªG¡C

¦ýLebrikizumab¤T´ÁÁ{§É¡A«e16¶g¨ÃµL¥|¶g¤@°wªº¹ê»Ú²Õ¡A

¦Ó¬O²Ä¤T­Ó¤T´ÁÁ{§É¡A©µ¦ù¸ÕÅç ¡A18~52¶g

¦p«e16¶gEASI ¡Ö50%ªÌ¡A¦w±Æ¦b20~52¶g¡A250mg/4¶g¤@°w¡C

¦p«e16¶gEASI ¡Õ50% , 18~52 ¶g 250mg/2¶g¤@°w¡C

Tralokinumab ªº16¶g«á¦Ü52¶gªº©µ¦ù¸ÕÅç¡A®ÄªG¤]¤£¿ù¡A

Significantly greater IGA 0/1 and EASI 75 response rates at week 16 were observed with tralokinumab with and without topical corticosteroids, when compared with placebo.

In ECZTRA 1, 15.8% of patients taking tralokinumab had an IGA 0/1, compared with 7.1% on placebo (P = .002), and 25.0% had an EASI 75 versus 12.7% with placebo (P < .001).

In ECZTRA 2, the IGA 0/1 proportion was 22.2% versus 10.9% (P < .001), and EASI 75 proportion was 33.2% versus 11.4% (P < .001).

For ECZTRA 3, the respective proportions were 38.9% versus 26.2% (P = .015) for IGA 0/1 and 68.0% versus 36.7% (P < .001) for EASI 75.

Lebrikizumab 2b ¤¤-­««×AD Á{§Éªº«ü¼Ð(2019/3¤ë¤½¥¬)

(¤@).250 mg Q2W(¨â¶g¤@°w)

EASI-50 81.0%***

EASI-75 60.6%***

EASI-90 44.0%***

IGA0/1 44.6%**

(¤G).250 mg Q4W(¥|¶g¤@°w)

EASI-50 77.0%**

EASI-75 56.1%**

EASI-90 36.1%**

IGA0/1 33.7%*

(¤T)¹ï·Ó²ÕPlacebo

EASI-50 45.8%

EASI-75 24.3%

EASI-90 11.4%

IGA0/1 15.3%

*p<0.05, **p<0.01, and ***p<0.001 versus placebo

www.businesswire.com/news/home/20191017005896/en/Dermira-Presents-Data-Phase-2b-Study-Lebrikizumab

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Primary Outcome Measures :

To assess the safety and tolerability of multiple ascending doses of ASLAN004: Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Baseline to 12 weeks safety follow up ]

Incidence of treatment-emergent adverse events (TEAEs) reported from the administration of study drug on Day 1 until the completion of the study.

µû¦ô¦h¦¸»¼¼W¾¯¶qªºASLAN004ªº¦w¥þ©Ê©M­@¨ü©Ê¡GªvÀøºò«æ¤£¨}¨Æ¥ó¡]TEAE¡^ªºµo¥Í²v[®É¶¡½d³ò¡G°ò½u¦Ü12¶g¦w¥þÀH³X]

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clinicaltrials.gov/ct2/show/NCT04090229

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Secondary Outcome Measures :

Percentage change from baseline in Eczema Area and Severity Index (EASI) score weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]

Proportion of patients with 50%, 75%, and 90% improvement in the EASI score (EASI50, EASI75, and EASI90) weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]

Percentage change from baseline in the Pruritus Numerical Rating Scale (NRS) score weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]

Proportion of patients with at least a 4-point improvement in the Pruritus NRS score weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]

Proportion of patients who achieve an Investigator Global Assessment (IGA) score of 0 or 1 weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]

Percentage change from baseline in the Patient-Oriented Eczema Measure (POEM) weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]

Percentage change from baseline in percent body surface area (%BSA) affected weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]

PK parameters throughout the dosing period, and serum concentrations by scheduled timepoints. [ Time Frame: Baseline to 12 weeks safety follow up ]

Measurement of area under the curve (AUC) at Week 8 (AUC0-last), maximum observed concentration (Cmax) at Week 1, time to Cmax (tmax) at Week 1, Ctrough throughout the dosing period, and serum concentrations by scheduled timepoints.

Change from baseline in PD markers of allergic inflammation (TARC and total IgE) weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]

Measurement of absolute values of TARC and total IgE in serum concentration and percentage of change

Measurement of ASLAN004 Anti-Drug Antibody over time. [ Time Frame: Baseline to 12 weeks safety follow up ]

Measurement of ADA levels in serum

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