Biosimilar Reports - April 2016 Save

Major advances in biosimilars have occurred in the last three months, beginning with the FDA Arthritis Advisory Committee voting 21-3 to approve Celltrion’s Inflectra (CT-P13) and ending with the recent approval of Inflectra (generically referred to as infliximab dyyb).

Biosimilars continue to command a great deal of attention given the promise of significant cost savings and potentially wider use for those in need.

RheumNow will periodically review this subject with “Biosimilar Reports” that provide updates, news, new publications, overview articles and research results impacting to biosimilar development and use. Many of these items were compiled from news sources, journal articles and regulatory documents.

News

1. IMS Institute for Healthcare Informatics has reported that the introduction of biosimilars in the US and Europe's five top markets could result in a $110 billion ($98 billion euros) savings by 2020. http://buff.ly/1qqvX5I
2. While some sources estimate biosimilars could save as much as $250 billion over the next decade, the Congressional Budget Office estimates a 10-year savings of around $25 billion. In contrast, the American Action Forum provided a much lower savings estimate for biosimilars, hypothesizing a figure between $5.1 billion and $37.8 billion on drug expenditures from 2015 through 2024. http://buff.ly/1SNnzo0
3. During a recent Senate hearing, Janet Woodcock, MD and Sen. Christopher S. Murphy (D-Conn.) agreed that while biologic therapies comprise less than 1% of the U.S. health care prescription drug market, these treatments account for 28% of prescription drug spending and that both the frequency of use and costs are likely to increase. During the same hearing, Sen. Elizabeth Warren (D-Mass.) said eight biologic drugs comprise 40% of all Medicare Part B spending, and biosimilars are projected to save $44 billion during the next 10 years.
4. Until last week, there was only one biosimilar approved in the U.S. – Zarxio (a Neupogen biosimilar). In Europe there are over 20 approved biosimilars
5. Express Scripts estimates the U.S. will save $22.7 billion with the approval of biosimilar versions of Neupogen ($5.7 billion) and Remicade ($17 billion) in the first decade they are on the market.  
6. In 2014, worldwide sales of Remicade (infliximab) topped $9.88 billion, with more than $4 billion in U.S. sales.  The biosimilar of Remicade (Remsima, Inflectra) is approved by the European Medicines Agency (EMA) and is used in more than 60 countries. 
7. There are over 700 biosimilar products in preclinical and clinical trials. To date, 30 applications for biosimilar products have been evaluated in the European Union and 22 were approved across six classes. In the United States, the FDA reports that 59 proposed biosimilars for 18 different reference products are enrolled in its Biosimilar Product Development Program. 
8. A “First Take” podcast from Simon King and Matt Dennis after the approval of CT-P13 states the FDA has requested that Celltrion do a single “switch study” as part of their application.  They also surveyed rheumatologists and gastroenterologists following the FDA announcement and asked if switch data would make them more comfortable in changing from Remicade to Inflectra. Only 1/3 of respondents stated that switch data would be helpful. Hence, they suggest that education and experience will be necessary to ease the transition.  http://buff.ly/23wpc4o
9. In February 2016, the British Society of Gastroenterology issued a guidance document about switching patients from infliximab to CT-P13 (Remsima). The BSG concluded that there is sufficient data from observational studies to show that safety and clinical efficacy of CT-P13 are comparable to the originator drug, with similar immunogenicity, and that switching from Remicade to CT-P13 is also safe and effective.  Patients should be switched at the same dose and interval.  Automatic substitution at the pharmacy level without consulting the prescriber was stated to be inappropriate.  http://buff.ly/23wpOad
10. February 2016 Benepali, the first etanercept biosimilar, becomes available for use in the UK. http://buff.ly/1S8uKYd

Journal articles

1. Biosimilars: A Multidisciplinary Perspective.  Khraishi M, et al.  Clin Ther  2016 Mar 14. This is a comprehensive review of the biosimilar development process and their potential utility in clinical practice. Specifically, experts discuss clinical developments in the introduction of biosimilars across the disciplines of gastroenterology, nephrology, oncology, and rheumatology, and from a payer perspective, and also highlight a common need for ongoing pharmacovigilance, robust head-to-head clinical studies, and real-world data to establish the long-term risk-benefit profile of biosimilars. http://buff.ly/1TSFezn
2. Development of biosimilars.  Al-Sabbagh A, et al.  Semin Arthritis Rheum. 2016; 45 (5 Suppl):S11-8.  An overview of biosimilar manufacturing and development, including a review of regulatory guidelines and requirements. http://buff.ly/1VmUtSd
3. Clinical and regulatory perspectives on biosimilar therapies and intended copies of biologics in rheumatology. Mysler E, et al. This review covers the differences between biosimilars and intended copies, especially with regard to the differences in formulation, dosages, efficacy, or safety.  Rheumatol Int. 2016 Feb 27. http://buff.ly/22vUKBw
4. European Experience of Infliximab Biosimilars for the Treatment of Inflammatory Bowel Disease. Lakatos P, et al.  Biosimilar Q & A with Dr. Peter Lakatos (Head of Gastroenterology/Hepatology Unit and Endoscopy at Semmelweis University, in Budapest, Hungary). Questions about cost, reimbursement, acceptance and potential disadvantages. http://buff.ly/1N9HS2f
5. Biosimilar reading list.  http://buff.ly/1SNr79R

Overviews & Reviews

Critical Points to Consider about Biosimilars.  Amy Rhodes; The Rheumatology Network 3/16/16. Amy Rhodes reviews the clinical expanse of biosimilars world-wide, the regulatory issues, clinical trial designs, challenges to clinical practice and cost savings. http://buff.ly/1VmT3aD

Regulatory

1.  FDA issues new guidance document on Biosimilars. Citation source: http://buff.ly/263HBEo
   • This proposed draft guidance the FDA provides more details about how biosimilars will be regulated; specifically, how product labels and medication guides should be worded to include (or exclude) certain information present on the originator (reference) product label. A comment period is open for the next 60 days. The FDA has not yet issued guidance on the issue of “interchangeability,” but promises to deliver this sometime in 2016.  Interchangeability is defined as the ability of the biosimilar to produce “the same clinical results as the reference product in any given patient and that switching between the two is safe.”  Hence, the full financial benefits to be achieved with biosimilars will not be fully realized until interchangeability is established and working.
   • Some of the main takeaways include that the label should indicate if the biosimilar has not been approved for the same uses as the reference product.  Another issue states the label should refer to the nonproprietary name designated by the FDA for the reference product when sharing information about clinical studies or data that came from studies using the reference product.
   • New terminology was also reviewed and covered naming - the proprietary (branded) name; proper name, and core name. A fictional originator product given the nonproprietary (generic) name of “replicamab” and branded (trade) of “Junexant,” can be followed by a biosimilar with a new branded name of “Nexsymeo.” Junexant will have a proper name of “replicamab-hjxf,” and Nexsymeo will have a proper name of “replicamab-cznm.” Both have the core name of replicamab; the four-letter extension is a way to distinguish the original from the biosimilar. Other biosimilars of the same originator will have different 4 letter extensions. The four-letter extension is intentionally noninformational. http://buff.ly/263p6jy
2. Samsung Bioepis SB2 biosimilar of Remicade (Flixabi) has received a positive opinion from Europe’s EMA Committee for Medicinal Products for Human Use (CHMP) for use of SB2 in RA, Crohn’s, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. http://buff.ly/1Vs5qTh
3. Pfizer buys Hospira for $17 billion.
4. In Korea, Samsung Bioepis has launched its second biosimilar called Renflexis, a biosimilar of Remicade, at a 5% discount compared to Remicade. Samsung Bioepis (established in 2012) has previously launched a biosimilar of etanercept called Brenzys or Benepali. These have also been sold in Norway and the U.K.  http://buff.ly/1SNpysv
5. Novartis’ generic division, Sandoz, has acquired the rights for the development and commercialization of a biosimilar version of Remicade (infliximab) from Pfizer, Inc.   http://buff.ly/1S8vn3Y
6. Humira Spotlight.  Abbvie does $24 billion a year in annualized sales, with $14 billion coming from Humira (adalimumab) alone.  Read more: http://www.fool.com/investing/general/2016/01/30/abbvie-there-aint-no-st... AbbVie intends to vigorously defend the intellectual property of Humira according to Abbvie CEO Richard Gonzalez. While the composition patent for Humira was due to expire in December 2016, and in Europe in October 2018, but AbbVie intends to file new patents to extend the patent protection to somewhere between 2019 and 2022.  What will happen to the growth of adalimumab with the introduction of Humira biosimilars?  Humira leads the TNF inhibitors in worldwide sales. Wall Street analysts have projected that 2016 revenues could reach $15.7 billion. This annual growth rate of 11.8% is lower than that previously seen for Humira sales. 
7. Samsung Bioepis is suing Abbvie over Humira patent in the UK. http://buff.ly/1ScNg3H
8. Janssen is suing Celltrion over its infliximab biosimilar.  http://buff.ly/263FSPx
9. Sandoz has petitioned the US Supreme Court to review biosimilar launch rules that require a biosimilar manufacturer to give 180 days to the brand-name biologic manufactures before selling the biosimilar.  http://buff.ly/1Wu8RrJ

Clinical Trials

1. A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study.  Yoo DH, et al. Arthritis Research & Therapy 2016; 18:82  http://buff.ly/1ScKgnY
2. Switch data reported switching from Celltrion’s Remsima to Remicade in IBD patients. Data from the European Crohn’s and Colitis Organisation (ECCO) 2016 meeting. http://buff.ly/1SDH6ab