Author: Urszula Wojtyra
The following provides an overview of the many developments regarding biosimilars in Canada (approvals, pending submissions, regulatory, litigation and market access) that have taken place since our last update in October 2019.
Biosimilars approved by Health Canada
Thus far in 2020, Health Canada has approved seven biosimilars of six innovator products. This brings the total Health Canada approvals to 25 biosimilars of 12 innovator products. Below is a complete list:
|Biosimilar||Manufacturer and year of approval||Review time (from filing to the earlier of approval and IP hold, where available)||Medicinal ingredient||Marketed?|
|1||OMNITROPE||Sandoz, 2009||748 days||somatropin||yes|
|2, 3||REMSIMA/INFLECTRA||Celltrion, Hospira 2014||427 days||infliximab||yes (INFLECTRA)|
|4||BASAGLAR||Eli Lilly, 2015||356 days||insulin glargine||yes|
|5||GRASTOFIL||Apotex, 2015||1039 days1||filgrastim||yes|
|6||BRENZYS||Samsung Bioepis, 2016||358 days||etanercept||yes|
|7||ERELZI||Sandoz, 2017||353 days||etanercept||yes|
|8||ADMELOG||Sanofi-aventis, 2017||351 days||insulin lispro||yes|
|9||RENFLEXIS||Samsung Bioepis, 2017||793 days||infliximab||yes|
|10||HADLIMA, HADLIMA PUSHTOUCH||Samsung Bioepis, 2018||432 days||adalimumab||no|
|11||LAPELGA||Apotex, 2018||349 days||pegfilgrastim||yes|
|12||MVASI||Amgen, 2018||358 days||bevacizumab||yes|
|13||FULPHILA||Mylan, 2018||754 days||pegfilgrastim||yes|
|14||TRUXIMA||Celltrion, 2019||335 days||rituximab||yes|
|15||OGIVRI||BGP Pharma, 2019||356 days||trastuzumab||yes|
|16||ZIRABEV||Pfizer, 2019||336 days||bevacizumab||yes|
|17||TRAZIMERA||Pfizer, 2019||348 days||trastuzumab||yes|
|18||HERZUMA||Celltrion, 2019||324 days||trastuzumab||yes|
|19||OSNUVO||Avir Pharma, January 2020||637 days||teriparatide||no|
|20||KANJINTI||Amgen, February 2020||920 days||trastuzumab||yes|
|21||AVSOLA||Amgen, March 2020||351 days||infliximab||yes|
|22||NIVESTYM||Pfizer, April 2020||345 days||filgrastim||yes|
|23||ZIEXTENZO||Sandoz, April 2020||336 days||pegfilgrastim||yes|
|24||RIXIMYO||Sandoz, April 2020||795 days||rituximab||yes|
|25||RUXIENCE||Pfizer, May 2020||344 days||rituximab||yes|
According to Health Canada’s annual report, Health Canada approved eight biosimilar submissions in the 2019/2020 fiscal year, which runs from April 1, 2019 to March 31, 2020, and 11 in the fiscal year prior to that. Some of these are likely on IP hold.
Biosimilar submissions under review
Since October 2018, Health Canada provides a monthly update of new drug submissions under review (SUR) and identifies the sponsor, the filing date, and the submission class of the submission, including whether it is a biosimilar. The most recent SUR (as of August 19, 2020) identifies the following biosimilar submissions under review, which includes submissions on IP hold, with the number of submissions listed in brackets:
- Adalimumab (4)
- Bevacizumab (1)
- Enoxaparin sodium (3)
- Etanercept (1)
- Filgrastim (1)
- Insulin aspart (1)
- Pegfilgrastim (2)
- Rituximab (1)
- Trastuzumab (1)
There are also new drug submissions pending for the following: bevacizumab (1) and trastuzumab (3). These are likely biosimilars, but they are not specifically identified as such as they were filed prior to October 2018.
Since the last update, there was an increase in the number of biosimilar infringement actions, but most have been discontinued. The following are ongoing:
- Filgrastim and pegfilgrastim:
- In its first decision under the amended PMNOC Regulations, the Federal Court invalidated Amgen’s patent relating to the filgrastim drug NEUPOGEN in an action relating to Pfizer’s biosimilar NIVESTYM (as we reported here). Amgen has appealed. Following the Federal Court’s decision, Pfizer brought the first section 8 action under the amended PMNOC Regulations, claiming damages for delay in the issuance of Pfizer’s notice of compliance. Based on Health Canada’s summary basis of decision, Pfizer’s application was placed on IP hold in February 2019, and the NOC issued April 2020.
- Amgen has three pending pegfilgrastim biosimilar actions under the amended PMNOC Regulations against Pfizer (NYVEPRIA), Purdue Pharma (PELMEG), and Sandoz (ZIEXTENZO). The first action was stayed on consent; the trial for the second action is scheduled for October 2021; and the trial for the last action is scheduled to start in October 2020.
- Amgen has also sued BGP Pharma dba Mylan for patent infringement regarding the pegfilgrastim biosimilar FULPHILA, but this proceeding has been stayed pending appeal. Amgen had previously brought but discontinued an application under the pre-amended PMNOC Regulations in light of the Court’s dismissal of Amgen’s application against Apotex.
- Infliximab: In the patent infringement action between Janssen and Hospira relating to the biosimilar INFLECTRA, the Federal Court of Appeal released its decision on January 30, 2020, remitting for reconsideration to the trial judge certain issues relating to the validity of Janssen’s patent (see our article here). Janssen has applied to the Supreme Court of Canada for leave to appeal. The reconsideration will be heard for two days starting September 8, 2020.
On December 10, 2019, Canada, the United States and Mexico signed the Protocol of Amendment to the Agreement between the United States of America, the United Mexican States and Canada (commonly referred to as the USMCA) (see our article here). While the original USMCA, signed in 2018, required a Party to provide a data protection term for biologics of at least ten years from the date of first marketing approval, the final USMCA does not include this requirement. Current Canadian data protection law provides an eight-year data protection term (with a possible six-month paediatric extension) for both biologics and small molecule drugs.
In January 2020, the Canadian Agency for Drugs and Technologies in Health (CADTH) released a report titled Utilization of Innovator Biologics and Biosimilars for Chronic Inflammatory Diseases in Canada: A Provincial Perspective. The report is from a collaboration with researchers at the Ontario Drug Policy Research Network (ODPRN), which also released a similar report: Current and Prospective Utilization of Innovator Biologics and Biosimilars in Ontario. The reports examine utilization trends of innovator biologics and biosimilar versions of infliximab and etanercept, as well as the innovator biologic adalimumab, in rheumatic conditions and inflammatory bowel disease in Ontario. The takeaway messages from the ODPRN report were: biosimilar users accounted for a small proportion of overall biologic users, even among biologics with a currently available biosimilar; the data suggested that traditional formulary-based policies may not have a significant impact on biosimilar uptake; and the effect of policies on the uptake of biosimilars may differ by patient indication.
In 2019, the pan-Canadian Pharmaceutical Alliance (pCPA) engaged CADTH to conduct a stakeholder consultation on implementation and expanded use of biosimilars in Canada (Pan-Canadian Biosimilars Consultation Process 2019 website here). The presentations from the in-person session are available here, and include presentations from Health Canada and the Patented Medicine Prices Review Board (PMPRB). Two reports flowing from the consultation process are available: National Consultation on the Use and Implementation of Biosimilars: Online Consultation Summary Report and National Consultation on the Use and Implementation of Biosimilars: In-Person Consultation Summary Report. According to the pCPA website, the final report from the consultation was released in February 2020 to the pCPA and its member jurisdictions, but a copy was not available on the pCPA website or the Consultation Process website.
CADTH is preparing another report (see “Harmonization of Public Coverage Policies for Biologic Drugs in the Treatment of Rheumatoid Arthritis”) which aims to identify common criteria and to propose these to jurisdictions to align access to biologic drugs across all publicly funded drug plans in Canada for patients with rheumatoid arthritis. The report is expected to be completed in December 2020.
Provincial reimbursement update:
As reported in our last update, in Ontario, the reimbursement criteria for biosimilars for infliximab, etanercept and filgrastim are less restrictive for most indications as compared to the reference biologic. Similarly, rituximab biosimilars TRUXIMA, RUXIENCE and RIXIMYO are listed as Limited Use products, whereas the reference biologic RITUXAN is reimbursed under the Exceptional Access Program. Similar to other biosimilars, the Ministry has advised that it will not consider any new requests for the reference biologic RITUXAN for treatment-naïve patients or for patients who do not respond to biosimilars.
In 2019, the British Columbia PharmaCare instituted the Biosimilars Initiative for Patients to switch patients from certain reference biologics to biosimilars for certain indications. The second phase was completed on March 5, 2020. The BC Cancer agency has an Oncology Biosimilars Utilization Policy, pursuant to which patients starting a new treatment will only be funded for the listed biosimilars, which include bevacizumab, trastuzumab and rituximab biosimilars.
In December 2019, Alberta also instituted a Biosimilar Initiative pursuant to which patients were required to be switched from the reference biologic to a biosimilar for certain indications by July 1, 2020, extended to January 15, 2021 due to COVID-19. Additionally, a tiered framework will apply requiring cost-effective biologic agents to be used first for individuals starting a biologic or changing their biologic drug.
As part of the National Prescription Drug Utilization Information System (NPDUIS) initiative, the PMPRB released a two-part report, Biologics in Canada, 2018. Part 1: Market Trends, 2018 examines the Canadian market for biologics, with a comparison to international trends in sales, pricing and biosimilar uptake. Part 2: Biosimilar Savings, 2018 uses trends in Canada and internationally to examine cost savings that could be realized through increasing the uptake and/or lowering the prices of biosimilars in Canada.
Under the PMPRB’s revised draft Guidelines (reported here) to operationalize the amended Patented Medicines Regulations (which will be in force January 1, 2021), all new patented biosimilars will fall within “Category II” such that the price should be the lower of the list price and the Median International Price of the PMPRB11. However, an investigation into the pricing of patented biosimilars will only be initiated if a complaint is filed, even if the patented biosimilar otherwise meets the criteria for an investigation.
Should you have any questions, please do not hesitate to contact a member of the Life Sciences Regulatory & Compliance group.
1. Calculated based on the IP hold date (May 21, 2015) in Apotex’s statement of claim in Court File No. T-934-16.
The preceding is intended as a timely update on Canadian intellectual property and technology law. The content is informational only and does not constitute legal or professional advice. To obtain such advice, please communicate with our offices directly.