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Biosimilar Reports - February 2018

Biosimilars command a great deal of research, development and attention given the promise of significant cost savings and potentially wider use for those in need.  The global biosimilar market is expected to reach $36 billion USD by 2022. 

RheumNow’s Biosimilar Reports is an ongoing series dedicated to advances, discussions and developments in biosimilar agents intended for use by rheumatologists.  

RheumNow provides review this subject with updates, news, new publications, overview articles, clinical trial results, regulatory and legal issues impacting to biosimilar development and use. Many of these items were compiled from news sources, journal articles and regulatory documents and are cited and linked within each section.  

Clinical Trials & Journal Articles

DANBIO Non-Medical Switch Study: Glintborg et al reported the results of the DANBIO non-medical switch from originator infliximab to biosimilar CT-P13 in 802 inflammatory arthritis arthritis patients with RA, PsA, AxSpA who were previously treated with reference infliximab (INX) for 6.8 years and found that non-medical switch to CT-P13 had no greater flare rates or withdrawals than those on INX. 132 patients withdrew (lack of effect 54% or adverse events 28%). Patients with previous INX treatment duration >5 years had longer CT-P13 retention.

SB4 Measures Up.  Emery and colleagues have reported the results of a phase 3 trial wherein 596 moderate to severe RA patients (despite MTX treatment) received either etanercept (ETN) or the etanercept biosimilar, SB4. At 52 weeks comparable efficacy was observed for SB4 (80.8%) and ETN (81.5%).  Similarly, similar radiographic progression was also observed after 12 months (mTSS 0.45 for SB4 and 0.74 for ETN). While safety signals were equivalent, the incidence of anti-drug antibody 1% with SB4 and 13.2% in the ETN group, yet these differences yielded no clinical consequences.

Time Changes Biosimilar Attitudes.  The infliximab biosimilar CT-P13 (Remsima, Inflectra) was approved by the European Medicine Agency (EMA) in 2013 for the same indications as the reference drug, including pediatric inflammatory bowel disease (IBD) as the approval was based on extrapolation, and no clinical trials in pediatric IBD, there was significant concern about its adoption and use among pediatric gastroenterologists. The current report chronicles its adoption over a 4 year period during which postmarketing studies and real-life experience has led to the acceptance of CT-P13 as an Infliximab biosimilar. Curr Opin Pediatr. 2017

Drug Monitoring with Biosimilar Switching. An open label study of patients switching from Remicade (INF) to infliximab biosimilar (INB) collected serial blood samples before the switch and serially over the next 12 months. They analyzed drug trough levels, antibodies-to-infliximab, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and disease activity scores. 27 patients with a variety of rheumatic diseases had been on INF for 143 (58–161) months. Anti-drug antibodies were seen in 3 patients, and 7 patients (26%) discontinued the therapy for subjective reasons. Otherwise no difference were seen between INF and INB for  infliximab levels, CRP levels, and disease activity scores.

Overviews & Reviews

Obstacles to the Adoption of Biosimilars. JAMA article on biosimilar adoption revealed that biosimilars accounted for 22% of all new US drug approvals from 2010-2015 and comprising 28% of overall prescription drug revenue in 2015. The Biologics Price Competition and Innovation Act (part of the Affordable Care Act) paved the way for biosimilar development so as to facilitate competition and cost savings marketed once the reference biologic goes off patent. It is estimated that biologics earning nearly $100 billion in worldwide sales are due to go off patent by 2020. While small molecule oral generics account for 88% of current prescriptions and have yielded $1.5 trillion savings over 10 years, the authors believe there are several obstacles to biologic adoption and savings, including: 1) there is no automatic pathway for biosimilar substitution and interchangeability; 2) physicians and patients are adverse to switching from a currently effective biologic to a biosimilar that will yield cost savings; and 3) rebate agreements between pharmaceutical companies, pharmacy benefit managers and insurers incentivizes the continued use of more expensive originator biosimilars. Such rebates may be as much as 50% of the drug cost. If the biosimilar maker steeply discounts their drug, the originator company may withdraw their rebate and the cost of the biosimilar may be more expensive to the PBM/insurer and ultimately the patient. Lastly, for the cost savings of biosimilars to be fully realized the prevalent biologic rebate system would need to be abolished to exclusive use of the cheaper biosimilar.

Why is Biosimilar Uptake Slow?  Researchers at Trinity Partners have compiled report based on interviews with medical directors at 10 top U.S. payers and have surmised there are 3 major obstacles to biosimilar uptake in the U.S – 1) Pricing agreements are complex, 2) doctors and patients remain dubious of the new alternatives and 3) makers of the original branded meds have put up a tough fight, both in court and in the promotional (advertising) sphere

Worldwide Guidelines and Regulations for Biosimilar Uptake in Psoriasis.  A multiauthored, multinational review discusses current biosimilar regulatory guidelines and variance of biosimilar uptake in clinical practice in several countries. It appears that biological therapy treatment decisions may become more physician independent. The International Psoriasis Council recommends that dermatologists should take an active role in the development of biosimilar prescribing policies with their respective healthcare settings and government agencies. Br J Dermatol. 2017 

EU Biosimilar Uptake Affected by Country Policies.  An article in PLOS One details some of the initiatives and regulations affecting biosimilars in the E.U. The article notes that specially physicians need to be informed on the entry and use of biosimilars in order to create trust. The paper provides recommendations on how the E.U. can develop a more stable market for biosimilars.

Practice & Physician Attitudes

ACR and AF Presidential Plea.  Dr. David Daikh (ACR president) and Ann Palmer (Arthritis Foundation President) have published a perspective article imploring change in the funding of arthritis research. They note that the CDC estimates that arthritis now represents a $300 billion annual burden to our economy (doubled over the past 15 years) and that 2/3 people living with arthritis are under 65, including roughly 300,000 U.S. children.  In their article they call for Congress to use existing funds to establish a $20 million dedicated arthritis research program at the Dept. of Defense to accelerate prevention strategies and treatment breakthroughs – for the servicemen and women whose bodies ultimately suffer from their selfless service.

Regulatory & Pharma

Senate Approves Azar for HHS Head. US Senate has voted to approve Mr. Alex Azar as Secretary of the U.S. Department of Health and Human Services (HHS). Azar was previously the President of Ely Lilly & Co.'s U.S. operations and before that served as HHS general counsel and deputy Secretary under President George W. Bush.  Azar is on record to tackle the rising costs of prescription drugs. insider knowledge "of how insurance, manufacturers, pharmacy and government programs work together” and will support policies to ensure robust market competition for both generic and brand-name drugs and to "create a viable and robust biosimilar market also, to compete against branded companies in that high-cost biologic space." 

FDA 2018 Roadmap.  Commissioner Scott Gottlieb announced his 2018 FDA policy roadmap that addressed the opioid crisis, leveraging innovation, drug competition to improve healthcare, educating consumers to make more informed choices about nutrition, and efforts to strengthening risk management. He also discussed the new “Biosimilar Innovation Plan” that will create better incentives for the development, approval and adoption of biosimilar drugs. The agency also plans to issue final guidance on how drug makers can communicate information to payers about products that could promote value-based contracting.

Rituximab Biosimilars. In January 2018 Pfizer announced the results of its REFLECTIONS rituximab biosimilar trial wherein its biosimilar (PF-05280586) was tested against MabThera (rituximab in the EU) and met its primary endpoint, the overall response rate (ORR) as first-line treatment of CD20-positive, low tumor burden, follicular lymphoma. Numerous other rituximab biosimilars are in development, including Amgen (ABP 798), Celltrion and Teva (approved in EU and filed with FDA in July 2017), Sandoz (approved in EU, filed with FDA September 2017). In response to IV rituximab going off patent, Roche has developed subcutaneous rituximab (Rituxan; MabThera).

Drug Approvals. There were 49 of the 2017 announcements involving the approval of a drug, expansion of a drug label or approval of a biosimilar, compared to 32 such announcements in 2016. There were 5 biosimilar approvals in 2017 – Renflexis (Infliximab-abda), Cyltezo (Adalimumab-adbm), Mvasi (Bevacizumab-awwb), Ogivri (trastuzumab-dkst) , and Ixifi (infliximab-qbtx).  Possibly the big standout in 2017 was the approval of the first 3 gene therapies.


The author has received compensation as an advisor or consultant on this subject

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