1、t the transition of certain products from the drug to biological pathway FDA released revised guidance on Nonproprietary Naming of Biological Products where the retrospective requirement for renaming already licensed biologics with four letter suffix has been removed Commercial Developments In the U
2、S, the impact of biosimilar versions of Remicade continues to be far less than expected, with JNJs brand still holding onto 92% of infliximab molecule share in 1Q19. On the other hand, Coherus pre- announced better-than-expected net sales for Udenyca (biosimilar Neulasta) of $36-38MM in 1Q19 In the
3、EU, ABBV has seen greater than expected erosion of Humira to biosimilars in the US, with the company now guiding to 30% erosion in international Humira sales in 2019, which will likely moderate in 2020 and beyond Source: FDA, EMA, Company data and Credit Suisse Analysis Recent Developments 3 Progres
4、s on Legal Front Remains Critical for Biosimilar Advancement, With Some Recent Developments and More Expected Soon Legal Developments In Walgreens/Kroger vs JNJ Remicade antitrust litigation, the district court in March ordered that judgement be entered in favor of JNJ on all counts granting the arg
5、ument that the plaintiff lacks antitrust standing. We continue to believe that the PFE vs JNJ case related to Remicade will set the precedent for such cases in future In Novartis vs Amgen Enbrel BPCIA case, post-trial briefing on the case was completed in December and a decision from the court is aw
6、aited anytime now Pfizer and Coherus settled with AbbVie, allowing their Humira biosimilars to be launched in the US in 2023 Six class action lawsuits were filed by unions and municipalities alleging violation by ABBV of antitrust and consumer protection laws by extending Humiras exclusivity with ov
7、erlapping and non-inventive patents and we expect more such suits to follow In a first biosimilar vs biosimilar case, Coherus sued Amgen in the US, alleging that Amgens Humira biosimilar infringes on its three patents regarding formulations of adalimumab and seeks to stop manufacturing the product i
8、n the US for sale in Europe without a license Source: FDA, EMA, Company data and Credit Suisse Analysis Recent Developments 4 Executive Summary Biosimilars Finally Prepared to Make Their Mark The authors of this report wish to acknowledge the contribution made by Selvakumar Nallasamy and Paul Singh,
9、 employees of CRISIL Global Research and Analytics, a business division of CRISIL Limited. CRISIL Limited is a third-party provider of offshore research services to Credit Suisse. 5 Greater Proportion of Branded Prescription Drug Sales Coming from Biologics and Complex Molecules Source: Credit Suiss
10、e PharmaValues Database and Credit Suisse Analysis Global Branded Prescription Drug Sales Estimate by Molecule Type (Sales in $ Bn) $0 $100 $200 $300 $400 $500 $600 $700 $800 $900 20102011201220132014201520162017201820192020202120222023 Small MoleculeBiologics/Complex moleculesVaccinesOthers Note: T
11、hroughout the analyses in this note, complex small molecule drugs (ex: Copaxone, Invega Sustenna) are classified under the biological category An estimated $113Bn of $299Bn (based on 2022 sales) in annual global biological sales is expected to no longer have patent protection by 2023, leaving door w
12、ide open for biosimilar competition Biosimilars Market Opportunity 6 Now in the Middle Innings of a Robust Period of Patent Expiries for Branded Biologic Products Source: Credit Suisse PharmaValues Database and Credit Suisse Analysis Sales During the Year Before Patent Expiry of Biologics Whose Pate
13、nt Expire By 2023 (Year of Patent Expiry in X axis; Prior Year Sales in $ Bn in Y axis) 20102011201220132014201520162017201820192020202120222023 Ex-US$0.8$0.7$5.2$2.0$11.8$13.4$0.6$4.9$12.3$5.0$2.4$3.0$5.0$2.6 US$0.7$0.3$3.5$2.2$2.3$12.7$0.9$10.9$7.5$12.6$2.9$3.1$5.7$17.2 $0 $5 $10 $15 $20 $25 $30 U
14、SEx-US Notable products include Humira (US), Victoza (US) and Benlysta (US) Notable products include Lantus, Enbrel (Ex-US), Neulasta (US), Remicade (Ex- US) and Epogen (US) Notable products include Humira (Ex-US), Remicade (US), Avastin, Herceptin (US) , Novolog, Rituxan (US) and Copaxone (US) No o
15、f patent expiries, US 1 (0) 1 (0) 4 (1) 3 (1) 3 (1) 8 (3) 3 (0) 7 (3) 7 (2) 11 (5) 5 (1) 5 (1) 4 (1) 7 (2) No of patent expiries, ex-US 2 (0) 1 (0) 8 (2) 5 (1) 6 (4) 10 (5) 3 (0) 9 (1) 8 (2) 13 (1) 6 (0) 5 (1) 8 (2) 5 (1) Note: Numbers in the parentheses denote the number of patent expiries of block
16、buster drugs (Sales $1bn) Biosimilars Market Opportunity 7 Roche, AbbVie Have Most Absolute Sales At Risk From Biologic Patent Expiries, While Novo and AbbVie Have Highest Portion of Sales At Risk Source: Credit Suisse PharmaValues Database, Thomson Eikon, First Order Analytics and Credit Suisse Ana
17、lysis $14.6 $12.6 $7.3 $9.1 $3.4 $5.8 $4.1 $2.5$2.4 $0.6 $2.2 $1.0$0.9 $0.7$0.2 $13.0 $6.3 $7.5$3.9 $7.4$2.5 $2.8 $3.1 $1.3 $2.6 $1.0 $2.1$2.1$2.3 $2.3 $0 $4 $8 $12 $16 $20 RocheAbbVie Inc. Novo Nordisk Johnson -29% (YoY) FY2017 (vs 14): -65%; -34% (YoY) FY2018 (vs 14): -75%; -31% (YoY) Remicade (JN
18、J/MRK) 15 Enbrel is Slowly Conceding to Biosimilars in the EU, While The Court Decision is Awaited To Decide Timing of First US Biosimilar Enbrel is experiencing gradual erosion in the EU as reported by PFE PFE lost almost half of Enbrel sales in the two years since launch of first biosimilar Benepa
19、li in Jan 2016 and are expecting 15% sales decline per year due to biosimilar competition PFE has taken mandatory price cut in some of the European countries after the launch of Enbrel biosimilars and believe that their net price is competitive Novartis has the first Enbrel biosimilar approved in th
20、e US, but are fighting AMGN in Court to clear the patent hurdle and subsequently launch their biosimilar AMGN asserts validity of two key patents expiring in 2028 and 2029 Novartis has agreed not to launch their biosimilar and the timeline of which is not disclosed Post-trial briefing on the case wa
21、s completed in December and a decision from the court is awaited now Source: Evaluate Pharma, BLOOMBERG PROFESSIONALTM service, Company data and Credit Suisse Estimates -24%(YoY) FY2018 (vs 15): -46%; -18%(YoY) 17 Limited Development of Biosimilar Versions of Stelara Potential Positive for JNJ, But
22、Impact Likely Still to Be Felt From Biosimilar Anti-TNFs Based on our review, we believe there are no Stelara biosimilars in mid-to-late stages of development There are five biosimilars in pre-clinical development that could emerge as potential competitors after Stelaras patent expires in Sept 2023
23、in the US and Jan 2024 in the EU ABBVs settlements to delay Humira biosimilars in the US until 2023 also benefits Stelara, as it delays indirect competition. Starting in 2023, we would expect that the entry of biosimilar versions of ABBVs Humira will impact the immunology space as a whole, and also
24、negatively pressure Stelara sales in the US (even without direct biosimilar Stelara competition) Source: Evaluate Pharma, First Order Analytics, Company data and Credit Suisse Estimates 2018: -47%) One approved in the US (2019 LoE) by Celltrion and we expect launch in 1H19 CS forecast global sales w
25、ill reduce by 65% from its peak by 2023 to $2.6bn The Roche defense: Subcutaneous (SC): The SC formulation is priced at a premium to the IV formulation but it saves time US: CSE 4Q19 HER2+ targeting therapy sales (Sales in $mn) Herceptin WW Sales Estimates (Sales in $Bn) CompanyProductUSEUJapan Cell
26、trion/Teva/Purdue/ Nippon Kayaku HerzumaApprovedMarketedMarketed Mylan/BioconOgivriApprovedApprovedPhase III PfizerTrazimeraApprovedApprovedApproved Allergan/Amgen/Daiichi/SynthonKanjintiFiledMarketedMarketed Merck/Biogen/SamsungOntruzantApprovedMarketed Prestige BioPharmaHervelousPhase IIIPhase III
27、 MabionMabionHER2Phase III 21 Avastin the Last of the Three Key Roche Franchises to Face Biosimilars Sources: Evaluate Pharma, BLOOMBERG PROFESSIONALTM service, Company data and Credit Suisse Estimates US: CSe c.July 2019 Avastin (Roche) CompanyProductUSEUJapan Allergan/Amgen/DaiichiMvasiApprovedApp
28、rovedPhase III AstraZeneca/FUJIFILM/KyowaFKB-238Phase IIIPhase IIIPhase III PfizerZirabevFiledApprovedPhase III Mylan/BioconKrabevaPhase IIIPhase IIIPhase III OutlookONS-1045Phase IIIPhase III CelltrionCT-P16Phase III BoehringerBI 695502Phase III Insud PharmaBevaxPre-clinicalPhase III Biogen/Samsung
29、SB8Phase III 22 $4.3 $3.6 $3.0 $2.6 $2.3 $0 $1 $2 $3 $4 $5 20182019202020212022 Neulasta Faces Its First Biosimilar Competitor While AMGN Tries to Limit Erosion With its On-Body Injector Device Mylan launched the first Neulasta biosimilar in the US in 3Q18 followed by the second one from Coherus in
30、Jan 2019 and AMGN expects more competition before the end of 2019 Coherus highlighted that the Neulasta treatment is episodic nature with high patient turnover. This is an advantage for the Neulasta biosimilars that they can make new patients to start with biosimilars and capture a greater market wh
31、ile other biosimilars that target treatment of ongoing nature are struggling to convert the existing patients In an effort to protect Neulasta sales from biosimilar competition, AMGN launched Neulasta Onpro kit, an on-body injector device Launched in the US in Aug 2015 and as of 4Q18 accounts for mo
32、re than 60% of the total Neulasta units sold in the US Approved in the EU in 2Q18 and already launched in some of the European countries as the company expects to convert Neulasta patients in the new markets to the new Onpro kit We believe patents on the device could extend out to 2030+. Biosimilar
33、manufactures looking to launch a biosimilar Neulasta may need to navigate around patents on the device/end up offering a product that is administered in a less attractive manner Source: Evaluate Pharma, BLOOMBERG PROFESSIONALTM service, Company data and Credit Suisse Estimates Were committed to adva
34、ncing policies that help make that more efficient” “Biosimilars not only present opportunities for significant cost savings, they can dramatically expand patient access to therapies” “Millions of American patients stand to benefit from increased utilization of lower-cost, high quality biosimilar pro
35、ducts” “FDA is invested in making sure the new biosimilar pathway works, and that we can help facilitate a robust market for these products” “We must do more to ensure current pipeline of biosimilar products reaches patients as safely and efficiently as possible, and that the full potential of biosi
36、milar products to improve patient health is realized once products meet the FDAs high standards for approval” “FDA will do its part by laying out an efficient path for showing how biosimilar products can demonstrate interchangeability” His speech to The Brookings Institution was on maintaining balan
37、ce between innovation and competition “ot;ws from io import StringIO def reraise(tp, value, tb=None): if value._traArticles Published online May 22, 2020 https:/doi.org/10.1016/S0140-6736(20)31208-3 1 Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vacci
38、ne: a dose-escalation, open-label, non-randomised, first-in-human trial Feng-Cai Zhu*, Yu-Hua Li*, Xu-Hua Guan, Li-Hua Hou, Wen-Juan Wang, Jing-Xin Li, Shi-Po Wu, Bu-Sen Wang, Zhao Wang, Lei Wang, Si-Yue Jia, Hu-Dachuan Jiang, Ling Wang, Tao Jiang, Yi Hu, Jin-Bo Gou, Sha-Bei Xu, Jun-Jie Xu, Xue-Wen
39、Wang, Wei Wang, Wei Chen Summary Background A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syn
40、drome coronavirus 2 (SARS-CoV-2) strain. Methods We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5
41、 10, 1 10, and 15 10 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses indu
42、ced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. Findings Between March 16 and March 27, 202
43、0, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 363 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse
44、reaction within the first 7 days after the vaccination was reported in 30 (83%) par ticipants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (5
45、4%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 46%), fatigue (47 44%), headache (42 39%), and muscle pain (18 17%. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted wi
46、thin 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. Interpretation The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adu
