Canada: Update On Biosimilars In Canada – October 2019

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 June 2018.

Biosimilars approved by Health Canada

Thus far in 2019, Health Canada has approved five biosimilars of three innovator products. This brings the total Health Canada approvals to 18 biosimilars of 11 innovator products. Below is a complete list:

1 Calculated based on the IP hold date (May 21, 2015) in Apotex's statement of claim in Court File No. T-934-16.

According to Health Canada's annual report, Health Canada approved 11 biosimilar submissions in the 2018/2019 fiscal year, which runs from April 1, 2018 to March 31, 2019, and seven in the fiscal year prior to that. Six 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 September 13, 2019) identifies the following biosimilar submissions under review along with the month in which each submission was accepted for review:

• adalimumab - Sandoz, November 2018
• filgrastim - Tanvex Biopharm, March 2019
• infliximab - Amgen, May 2019
• pegfilgrastim - Sandoz, May 2019
• rituximab - Pfizer, March 2019.

There are also new drug submissions pending for the following: bevacizumab (1), filgrastim (1), rituximab (1), teriparatide (1) and trastuzumab (5). These are likely biosimilars, but they are not specifically identified as such as they were filed prior to October, 2018.

Health Canada news

On August 27, Health Canada published an updated Biosimilar biological drugs in Canada: Fact Sheet. The Fact Sheet provides an overview of the regulatory framework for biosimilar drugs in Canada, including the approval process at Health Canada, how safety is monitored and how interchangeability and switching are governed at the provincial level.

Earlier in the year, Health Canada announced its Policy Statement on the Naming of Biologic Drugs (see article), which states that "biologic drugs, including biosimilars, will be identified by their unique brand name and non-proprietary (common) name, without the addition of a product-specific suffix" (currently used in the United States). Further, both the brand and non-proprietary names should be used throughout the medication use process to allow biologics that share the same non-proprietary name to be distinguished by their unique brand names.

In terms of approvals, according to Health Canada's Regulatory Decision Summaries (RDS):

• A drug referencing a biologic may be reviewed as a generic pharmaceutical product rather than a biosimilar: For example, Teva has received an approval for TEVA-TERIPARATIDE for which the Canadian Reference Product was Eli Lilly's FORTEO. While FORTEO is a biologic product, TEVA-TERIPARATIDE, produced using solid phase chemical synthesis, was classified as a pharmaceutical drug substance rather than a biologic and therefore was approved using the abbreviated new drug submission (ANDS) pathway (see RDS). See also the TEVA-LIRAGLUTIDE pending ANDS discussed below.
• A biosimilar approved in other countries may not be approved in Canada: While Mylan's SEMGLEE (a biosimilar of LANTUS, insulin glargine) is approved by the European Medicines Agency, BGP Pharma cancelled its submission prior to Health Canada rendering a final decision. According to the RDS, Health Canada had issued a Notice of Deficiency and found that the clinical data was inadequate to address Health Canada's concerns. Additionally, the chemistry and manufacturing data were deficient.

Biosimilar Litigation

Many of the cases reported in our previous update have been discontinued. The following litigation continues:

Filgrastim and pegfilgrastim:

• Amgen has sued BGP Pharma dba Mylan for patent infringement in respect of the pegfilgrastim biosimilar FULPHILA. Amgen had previously sought an order under the pre-amended Patented Medicines (Notice of Compliance) Regulations (PMNOC Regulations) prohibiting the Minister of Health from issuing a Notice of Compliance (NOC) to Mylan, but discontinued the application in light of the Court's dismissal of Amgen's application against Apotex.
• Amgen also has ongoing patent infringement actions against Sandoz pursuant to the amended PMNOC Regulations in respect of Sandoz's proposed filgrastim biosimilar ZARXIO [1503-18] and pegfilgrastim biosimilar ZIEXTENZO [T-902-19]. The trials for both actions are scheduled to be heard together in April 2020, although Amgen has a motion scheduled to adjourn the latter trial.
• Lastly, the trial of Amgen's action against Pfizer under the amended PMNOC Regulations is scheduled for January 2020. Pfizer had unsuccessfully sought to dismiss the action as an abuse of process, and most recently, the Federal Court of Appeal dismissed Pfizer's appeal (see previous articles here and here).

Infliximab:

• As reported previously, Janssen was successful in its patent infringement action against Hospira in respect of Hospira's biosimilar INFLECTRA. The Federal Court of Appeal heard the appeal of this decision, and other related procedural decisions, on October 28 and 29, and reserved its decision. The trial of the remedy phase of the patent infringement action is scheduled to start in January 2020.

There is also litigation relating to Novo Nordisk's biologic VICTOZA (liraglutide) against Teva. Teva had filed an ANDS for its proposed TEVA-LIRAGLUTIDE product based on a comparison to VICTOZA. Novo Nordisk asserted that Teva ought to have filed a new drug submission, as is required for a biologic products, but Novo Nordisk was unsuccessful in its Court application challenging the decision of the Minister of Health to accept the submission for review as an ANDS (reported here). Novo Nordisk has sued Teva for patent infringement pursuant to the amended PMNOC Regulations, and the trial is scheduled for October 2020. Separately, Novo Nordisk has commenced another patent infringement action against Teva with respect to a patent not listed on the Patent Register. This first-of-its-kind action is permitted by section 8.2 of the amended PMNOC Regulations, which allows a first person/patentee to bring an infringement action regarding a patent not listed on the Patent Register once served with a notice of allegation.

Market Access

In September 2018, the pan-Canadian Pharmaceutical Alliance (pCPA) issued the Biologics Policy Directions & pCPA Negotiations, which outlines pCPA's policy as it applies to negotiations for reimbursement of biologics, including biosimilars. The policy includes a statement that offers for biologics that restrict or exclude biosimilars will not be considered and that switching of patients from a reference biologic to a biosimilar may be implemented. The pCPA also partnered with Cancer Care Ontario to create a pan-Canadian Oncology Biosimilars Initiative (pCOBI), which aims to ensure appropriate implementation and cost-effective use of therapeutic oncology biosimilars across Canada. The Initiative has released a Proceedings Report of a Summit it held in 2018, as well as a pan-Canadian Oncology Biosimilars Initiative Action Plan.

The Canadian Agency for Drugs and Technologies in Health (CADTH) released an Environmental Scan on International Policies on the Appropriate Use of Biosimilar Drugs. Our article here provides an overview of the Environmental Scan's analysis, grouped under the categories of (a) interchangeability, switching and substitution; (b) supply side policies (relating to drug pricing, procurement and pharmacy reimbursement and practices); and (c) prescribing incentives.

There has been a move to improve the efficiency of funding consideration of biosimilars. CADTH announced that as of June 1, 2019, it will no longer review biosimilars through the Common Drug Review (CDR) or the pan-Canadian Oncology Drug Review (pCODR). Subsequent to CADTH's announcement, the pCPA provided an update advising that absence of CADTH review will not impact when pCPA negotiations may be initiated. As such, a biosimilar sponsor may contact the pCPA up to six months prior to obtaining an NOC from Health Canada to start the negotiation process. The Ontario Ministry of Health issued a policy directive that announced that new approved biosimilars will not require a routine review by the Ministry's expert drug advisory committees.

At the provincial level, different provinces have instituted different policies for biosimilars to achieve cost savings:

• British Columbia PharmaCare instituted the Biosimilars Initiative for Patients to switch patients from using certain reference biologics to biosimilars for certain indications.
• While the Quebec Minister of Health and Social Services sought to halt coverage of REMICADE, with certain exceptions, the Quebec Court of Appeal found the Minister's decision to delist REMICADE invalid and Quebec reinstated the listing (see our article here).
• In Ontario, the Ministry of Health reimburses infliximab biosimilars (RENFLEXIS, INFLECTRA) and etanercept biosimilars (BRENZYS, ERELZI) as Limited Use products for many of the indications of the reference biologics. The reference biologics (REMICADE and ENBREL, respectively) are reimbursed under the Exceptional Access Program (with the exception of ENBREL for severe plaque psoriasis, which is funded as a Limited Use product). Similarly, the filgrastim biosimilar GRASTOFIL is funded as a General Benefit, whereas NEUPOGEN is only funded as a Limited Use product. With some exceptions, the Ministry will not consider any new requests for the reference biologics for treatment-naïve patients or for patients who do not respond to biosimilars. However, the Ministry will generally not require switching of patients who have existing Exceptional Access Program approval for the reference biologics.

The Patented Medicine Prices Review Board (PMPRB) released the 5th Edition of CompassRx, the Annual Public Drug Plan Expenditure Report for 2017/18. The Report concluded that the total savings offered by biosimilars were limited, with the three biosimilars marketed by that timepoint "making a small but growing difference in overall drug costs." In a closer look at the disease-modifying antirheumatic drugs (DMARDs) market, the report found that once INFLECTRA, a biosimilar of REMICADE (infliximab), was introduced, the number of new patients using infliximab dropped from 23% to 12%, with half of those using INFLECTRA. However, other biologics grew their market share and occupied the share held by infliximab in previous years.

Competition Bureau

In terms of marketing practices, in February 2019, the Competition Bureau issued a statement providing guidance on some competition issues relevant to biologics and biosimilars. The statement outlined the various factors that may lead to fewer manufacturers developing biosimilar products (increased risk of failure, higher costs of manufacture and prolonged time for development and regulatory approval) and factors that may lead to lesser penetration in markets (lack of consensus about switching and the role of infusion clinics).

The Bureau advised that it will continue to monitor the biologic and biosimilar markets to ensure that companies do not engage in conduct that is having or is likely to have the effect of substantially lessening or preventing competition. In particular, the statement pointed to a likelihood of public and private payers implementing switching policies, noting that the Bureau will monitor reference biologic manufacturers' conduct in response. Conduct that could be anti-competitive may include spreading of false or misleading information about the safety and efficacy of biosimilars or entering into agreements with payers that have restrictions on reimbursement of biosimilars.

Conclusion

The past year has brought a number of developments relating to biosimilars. We anticipate that the next year will be as eventful. We will continue to monitor and report on future developments.

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.