PAAB Workshop. Advertising Jurisdiction Lead & Key Trend Advertising of Biosimilars. November 15, 2017

Transcription

1 PAAB Workshop Advertising Jurisdiction Lead & Key Trend Advertising of Biosimilars November 15, 2017 Alain Musende, PhD Manager, Therapeutic Effectiveness & Policy Bureau Health Canada

2 Purpose: To discuss: Jurisdiction lead associated with certain health products-related messages A key recent trend: advertising of biosimilars 2

3 Introduction Health Canada s Role National regulatory authority for health product advertising Sets the parameters under which health products are marketed in Canada (e.g. Product Monograph) Puts in place regulations to effectively regulate marketed health products Provides guidance documents for the interpretation of the regulations 3

4 Introduction (continued): Section 9(1) Food and Drugs Act Health Canada s commitment: Information in a health product advertisement should not be false, misleading or deceptive All promotional health product messages, irrespective of the media in which they appear, should comply with the legislative and regulatory advertising provisions and relevant Health Canada guidance documents on advertising 4

5 Context Dynamic interaction Health Canada Applicable Federal Statutes: -F&DA and R Guidance Documents -CDSA and NCR PAAB Code Health Product Association Codes Advertising P AAB Industry Healthcare Professionals/General Public APA: Advertising Preclearance Agency CDSA: Controlled Drugs and Substances Act F&DA and R: Food & Drugs Act and Regulations NCR: Narcotic Control Regulations 5

6 Why Regulate Health Product Advertising? To protect the health and safety of Canadians Mandated by law

7 Jurisdiction Lead Advertising is audience-based To Consumers To Healthcare Professionals 7

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9 Jurisdiction Lead (continued) PAAB provides formal review and preclearance service on all types of advertisements directed to healthcare professionals (HCPs), including: Branded pieces originally directed to the general public which are subsequently distributed to healthcare professionals and which are not to be re-distributed to patients1. Service-Oriented Vehicles to be used and distributed by HCPs (charts, brochures, diagrams, models, etc.) to encourage meaningful dialogue and to educate patients about a particular disease / condition and the optimal use of the product that has been prescribed (section of the PAAB Code). 1Disease information materials which make no mention of treatment by name, class, or category AND are not linked to health product advertising in any way, are exempt from PAAB preclearance. 9

10 Jurisdiction Lead (continued) PAAB also provides advisory opinions on pieces directed to the general public, including: Pieces distributed through healthcare professionals to consumers for whom a drug has not been prescribed. Pieces left in a waiting room of a physician s office. 10

11 Jurisdiction Lead (continued) Health Canada s Intervention: Intervenes when: PAAB is unable to obtain willful compliance Advertising contravenes regulatory requirements and poses a significant risk to health Advertising relates to incidents of illegal promotion (e.g., prescription drug advertising to the general public beyond name, price, and quantity, advertising of unauthorized products, off-label promotion, etc.) 11

12 Key Advertising Trend: Advertising of Biosimilars In this workshop, Health Canada will be discussing real examples of advertising complaints it has received: In the spirit of providing the audience with a meaningful educational content As requested by some members of industry, to prevent others from making similar mistakes 12

13 Advertising of Biosimilars (continued) The following criteria would apply: The selected complaints are all subject to a key consideration e.g. part of an advertising trend and the discussion of which could benefit other industry members Health Canada has already discussed the issue with the party involved The complaints have already appeared on Health Canada s table of advertising complaints ( 13

14 Advertising of Biosimilars (continued) Health Canada s position on biosimilars: patients and healthcare professionals can have the same confidence in the quality, safety and efficacy of a biosimilar as the reference biologic drug A biosimilar and the reference biologic drug are similar and there are no clinically meaningful differences in safety and efficacy between them The decision to switch a patient being treated with a reference biologic drug to a biosimilar should be made by the treating physician in consultation with the patient and taking into account available clinical evidence and any policy of the relevant jurisdiction. 14

15 Advertising Complaint #1: BRENZYS BRENZYS: Indication: Treatment of moderately to severely active rheumatoid arthritis in adults. Treatment is effective in reducing the signs and symptoms of RA, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function. BRENZYS can be initiated in combination with methotrexate (MTX) in adult patients or used alone. Reducing signs and symptoms of active ankylosing spondylitis. Market Authorization Holder: Merck Canada Inc. 15

16 BRENZYS: Advertisement media: Press Release on the CNW Group Web site Interview published in the Biotechnology Focus magazine 16

17 Monday, September 12, 2016 September 12, 2016 New Biosimilar can Offer an Effective and Lower Cost Treatment Option for Canadians Living with Rheumatoid Arthritis and Ankylosing Spondylitis KIRKLAND, QC, Sept. 12, 2016 /CNW/ - Merck (NYSE: MRK), known as MSD outside Canada and the United States, announced today that BRENZYS (etanercept) received approval in Canada for the treatment of adult patients with moderate to severe rheumatoid arthritis and ankylosing spondylitis. BRENZYS is a biosimilar to the originator biologic Enbrel * and the first subcutaneous anti-tumour necrosis factor (anti-tnf) biosimilar medicine available in Canada. "The approval of BRENZYS, biosimilar to etanercept, will allow cost savings for patients who require a biologic in the treatment of diseases such as rheumatoid arthritis and ankylosing spondylitis," said Dr. Janet Pope, Division Head in Rheumatology at St. Joseph's Health Centre, London. "The data demonstrated that BRENZYS had comparable efficacy and safety to the originator biologic Enbrel. Given that 4 of the top 5 selling drugs in Canada are biologics that can be used for the treatment of rheumatic diseases, the potential for biosimilars to reduce the cost of treating rheumatic diseases in Canada is significant. The Growth of Biologics in Canada One of Canada's fastest-growing segments in pharmaceutical spending, biologics showed a growth rate for the 12 months ending May 2016 of 9.7%,1 compared to the total market growth rate of 6.3%. The Impact of Biosimilars on the Healthcare System The cost of biologics affects provincial and private health plans. In the European Union and in Canada, biosimilars currently available are priced lower than their respective originator products, suggesting that their broader adoption would lead to cost savings. The recent decision of the majority of Canadian provinces to provide preferential listing for an anti-tnf biosimilar for patients starting a new biologic treatment regimen is a good step towards greater savings. However, most private drug programs in Canada have yet to follow the lead of their public counterparts in giving preference to biosimilars. An opportunity exists for more group benefit providers and plan sponsors to mandate the greater use of biosimilars and benefit from cost savings while maintaining the overall quality of employee plans. "More private drug programs in Canada should embrace biosimilar use in preferential listings as their public counterparts have already done with an anti-tnf biosimilar," said Bruno Mäder, Head of the Merck Biosimilars Business Unit in Canada. "Moreover, as real-world evidence accumulates, strong consideration should also be given to the potential transitioning of treatment-experienced patients receiving the originator biologic to the biosimilar, in order to create additional savings for the system. 17

18 Monday, September 12, 2016 September 12, 2016 About BRENZYS BRENZYS was approved in Canada on August 31, 2016 for the treatment of moderately to severely active rheumatoid arthritis (RA) in adults. Treatment is effective in reducing the signs and symptoms of RA, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function. BRENZYS can be initiated in combination with methotrexate (MTX) in adult patients or used alone. BRENZYS is also indicated for reducing signs and symptoms of active ankylosing spondylitis.5 BRENZYS is not indicated for use in children less than 18 years of age. Therefore, it should not be used for children less than 18 years of age. The recommended dose of BRENZYS for adult patients with rheumatoid arthritis, or ankylosing spondylitis is 50 mg per week.7 BRENZYS is provided as a single-use, pre-filled syringe or a single-use, pre-filled, auto-injector (both are latex-free). The auto-injector is button-free and is designed for ease-of-use for patients. For more information about BRENZYS, including details on the adverse drug reactions, please consult the product monograph. Clinical Data Highlights The approval of BRENZYS in Canada was supported by Samsung Bioepis' rigorous analytical, structural and functional testing, as well as a Phase I pharmacokinetics study and a Phase III clinical study comparing BRENZYS to the originator medicine, Enbrel. The phase III clinical study was a 52-week, double-blind, multicenter study that randomized 596 patients with moderate to severe rheumatoid arthritis despite methotrexate therapy.9 Analysis of the primary endpoint showed that BRENZYS had equivalent efficacy to Enbrel, as shown by an ACR response at week 24 of 78.1% in the BRENZYS arm vs. 80.5% in the Enbrel arm.10 The safety profile of BRENZYS was comparable to that of Enbrel throughout the study.11 The adverse drug reaction profiles reported in the clinical trials that compared BRENZYS to Enbrel did not show meaningful clinical differences. No new adverse reactions were reported.12 In the above mentioned phase III study, fewer injection site reactions for BRENZYS + methotrexate vs. Enbrel + methotrexate were reported: Injection site reactions in 11 patients (3.7%) vs. 51 patients (17.2% for Enbrel + MTX) (Most injection site reactions occurred early (between week 2 and week 8) and were mild in severity). At the EULAR 2016 congress, data was presented on the long-term safety and efficacy of BRENZYS in patients with rheumatoid arthritis in comparison between continuing BRENZYS and switching from Enbrel reference biologic to BRENZYS. Preliminary results on efficacy, safety and immunogenicity revealed no treatment-emergent safety or immunogenicity issues when transitioning patients from the originator product, Enbrel to the biosimilar product, BRENZYS. 18

19 Biotechnology Focus Magazine 19

20 Considerations: Merck s Messages Section 2 of the Food & Drugs Act Health Canada policy The Distinction Between Advertising and Other Activities 16

21 Section 2 of the Food & Drugs Act (continued) Section 2 Food and Drugs Act: Advertisement includes any representation by any means whatever for the purpose of promoting directly or indirectly the sale or disposal of any food, drug, cosmetic or device. Note: Health Canada uses the policy The Distinction Between Advertising and Other Activities to distinguish promotional campaigns from information. 21

22 The Distinction Between Advertising and Other Activities (continued) Brenzys Press Release Key Considerations: It is common practice for a pharmaceutical manufacturer to release information on new developments in research and at the time of launch of a new drug or a new indication for use of a previously authorized product. However, to remain non-promotional: The announcement should be limited to the name of the drug and its authorized or proposed therapeutic use No statement should be made regarding the degree of safety or efficacy expected No undue emphasis should be placed on the drug being a breakthrough 22

23 The Distinction Between Advertising and Other Activities (continued) The press release focused on Brenzys and included selected positive clinical data highlights with respect to the efficacy and safety of the product. No comparison should be drawn with other treatments The press release drew comparisons with other treatment options, which contributed to presenting Brenzys in a favorable light. There should be no attempt to influence the pick-up, placement or emphasis given in subsequent publication or broadcast The September 12, 2016 Brenzys press release was made available on the CNW Group Web site (newswire.ca) up until March The purpose of a press release is to provide new information. Press releases that are posted indefinitely no longer qualify as a news piece. 23

24 The Distinction Between Advertising and Other Activities (continued) Biotechnology Focus Interview Key Considerations: Who are the primary and secondary audiences? Intended audience (primary): professionals in the life science sector. Targeted audience (secondary): general public (unlimited in scope since it was made available on Biotechnology Focus Web site) What influence does a drug manufacturer have on the message content? Merck was given the opportunity to comment, revise and edit the content prior to publication in order to ensure consistency with the responses provided during the interview. 24

25 The Distinction Between Advertising and Other Activities (continued) What is the content of the message? The responses provided by the interviewee mainly focused on Brenzys, its efficacy and safety profile compared to the originator biologic, and its specific unique features The content of the interview mostly presented Brenzys in a more favorable light and contributed to leaving the impression that biosimilars, and mainly Brenzys, have only positive aspects, features and characteristics 25

26 Health Canada s Assessment Outcome: Merck Canada s: Press Release entitled New Biosimilar can Offer an Effective and Lower Cost Treatment Option for Canadians Living with Rheumatoid Arthritis and Ankylosing Spondylitis Interview entitled Merck scores its first biosimilar victory with Enbrel knockoff Brenzys Constitute advertising in accordance with: The Food & Drugs Act The Health Canada policy The Distinction Between Advertising and Other Activities 26

27 Applicable Contraventions Section C of the Food and Drug Regulations This provision restricts prescription drug advertising to the general public to the mention of the brand name, proper name, common name, and the price and quantity of the drug. The press release and the interview referred directly to the therapeutic indication of the product in a branded context and promote the availability of the prescription drug. 27

28 Section 9(1) of the Food and Drugs Act The press release and the interview provided clinical data highlights that were selected by the sponsor The press release and interview included preliminary results from ongoing studies in a promotional context and this may be deemed misleading The press release and interview seemed to suggest that Brenzys was bioequivalent to the originator biologic This is misleading as authorization of a biosimilar is not a declaration of bioequivalence to the reference biologic drug 28

29 Section 3 of the Food and Drugs Act The press release and interview promoted a health product for the treatment of rheumatoid arthritis, a Schedule A disease, to the general public. In this context, the press release was deemed to contravene section 3(1) of the Food and Drugs Act, which prohibits advertising of drugs for the prevention, treatment, or cure of any of the serious diseases listed in Schedule A to the Act, which includes rheumatoid arthritis. 29

30 Advertising Complaint #2: Neupogen Neupogen : Indication: Cancer Patients Receiving Myelosuppressive Chemotherapy NEUPOGEN (filgrastim) is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies (see Patients with Acute Myeloid Leukemia) receiving myelosuppressive anti-neoplastic drugs. NEUPOGEN is indicated in adult and pediatric patients with cancer receiving myelosuppressive chemotherapy. Market Authorization Holder: Amgen Canada Inc. 30

31 Neupogen : Advertisement media: The Globe & Mail: September 11 13, until October 11,

32 The Globe & Mail: September 11 13,

33 The Globe & Mail: September 11 13,

34 September 12, September 12, 2017 Attention Ontario Chemotherapy Patients Receiving Neupogen Ontario government has delisted Neupogen, a critical drug for chemotherapy treatment As of the end of August, the Ontario government will no longer cover Neupogen (filgrastim) for prophylaxis of febrile neutropenia for patients receiving chemotherapy with curative intent. This means that patients who are losing coverage for Neupogen under the Ontario Public Drug Programs will be forced to switch mid- treatment to a filgrastim biosimilar, Grastofil. The impact to a patient in switching from Neupogen to Grastofil mid-treatment has not been well-studied and patients may respond differently. In addition, for patients already dealing with a cancer diagnosis, the burden of various therapies and side effects from treatment, forcing a switch in therapy could impact their mindset, emotions and the success of their overall treatment. Further, Health Canada recommends that switching patients from an originator biologic medication (in this case, Neupogen ) to a biosimilar should be a clinical decision made by the treating physician in full consultation with the patient. Because filgrastim is a critical drug in oncology treatment, we believe it is important that patients and clinicians continue to have choice as to which filgrastim medication they receive. The Ontario government s decision to delist Neupogen no longer gives physicians and patients that choice. For this reason, Amgen Canada has made it a priority to work with the Ontario government to preserve physician and patient choice and secure multiple sources for drug supply. In the meantime, Amgen Canada has made the decision to make Neupogen available to Ontario patients who are currently in mid-treatment with Neupogen, right up until the end of their treatment. This will be at no cost to the patient and will provide patients the opportunity to avoid a treatment switch that could potentially put their current treatment plan in jeopardy. We will continue to place priority on working with the Ontario government to do what is best for patients, particularly given the severity of these concerns. In the meantime, if you or your patients currently use Neupogen, please contact the Victory Patient Support Program at , or online at Sincerely, Francesco Di Marco General Manager, Amgen Canada 34

35 Considerations: Amgen s Message Section 2 of the Food & Drugs Act Health Canada policy The Distinction Between Advertising and Other Activities 16

36 Section 2 of the Food & Drugs Act (continued) Section 2 Food and Drugs Act: Advertisement includes any representation by any means whatever for the purpose of promoting directly or indirectly the sale or disposal of any food, drug, cosmetic or device. Note: Health Canada uses the policy The Distinction Between Advertising and Other Activities to distinguish promotional campaigns from information. 36

37 Section 2 of the Food & Drugs Act (continued) Section 2 Food and Drugs Act: sell includes offer for sale, expose for sale, have in possession for sale and distribute, whether or not the distribution is made for consideration. 37

38 Section 2 of the Food & Drugs Act (continued) Key Consideration: Amgen Canada has made the decision to make Neupogen available to Ontario patients who are currently in mid-treatment with Neupogen, right up until the end of their treatment. This will be at no cost to the patient and will provide patients the opportunity to avoid a treatment switch that could potentially put their current treatment plan in jeopardy Promoting the distribution of Neupogen 38

39 The Distinction Between Advertising and Other Activities (continued) Key Considerations: Who are the primary and secondary audiences? Intended audience (primary): Ontario chemotherapy patients receiving Neupogen Targeted audience (secondary): general public (unlimited in scope) Who sponsors the message and how? The message was sponsored by Amgen With what frequency is the message delivered? The message was delivered repeatedly (3 successive days in the Globe & Mail and continuously on Amgen s Web site) What is the content of the message? The message was focussed on Amgen s product in a context attempting to put Neupogen in a better light compared to the competitor s product Grastofil 39

40 Health Canada s Assessment Outcome: Amgen Canada s message entitled Attention Ontario Chemotherapy Patients Receiving Neupogen constitutes advertising in accordance with: The Food & Drugs Act The Health Canada policy The Distinction Between Advertising and Other Activities 40

41 Applicable Contraventions Section C of the Food and Drug Regulations This provision restricts prescription drug advertising to the general public to the mention of the brand name, proper name, common name, and the price and quantity of the drug. The ad and letter refer directly to the therapeutic indication of the product in a branded context and promote the availability of the prescription drug. 41

42 Applicable Contraventions Section 9(1) of the Food and Drugs Act Although it is factual that Neupogen is no longer on the Ontario Public Drug Programs list, the message is conveyed within an alarmist context, which may contribute to create unnecessary concerns, confusion and anxiety amongst Neupogen patients Supported by statements such as: The impact to a patient in switching from Neupogen to Grastofil mid-treatment has not been well-studied and patients may respond differently Forcing a switch in therapy could impact their mindset, emotions and the success of their overall treatment 42

43 Applicable Contraventions Section 3 of the Food and Drugs Act Since Amgen s ad indicates that Neupogen is a drug taken during chemotherapy treatment and that cancer patients have relied on it for years, it is considered part of the treatment regimen against cancer In this context, the ad and letter are deemed to contravene section 3(1) of the Food and Drugs Act, which prohibits advertising of drugs for the prevention, treatment, or cure of any of the serious diseases listed in Schedule A to the Act, which includes cancer 43

44 Conclusion: A biosimilar and its reference biologic drug can be shown to be similar, but not identical. Accordingly, claiming or insinuating, in advertising, that a biosimilar is: Identical to its reference biologic Is false & misleading Different from its reference biologic Switching from the reference biologic may be dangerous and/or compromise the treatment outcome Is false & misleading 44

45 Conclusion (continued) Health Canada is committed to protecting the health and safety of Canadians by: Maintaining regulatory standards for the advertising of health products Taking regulatory actions when non-compliance is identified Health Canada recommends that industry uses the voluntary but valuable preclearance service offered by PAAB Health Canada values the collaborative work with the PAAB and industry to accomplish this goal 45

46 Contact Alain Musende, PhD Manager, Therapeutic Effectiveness & Policy Bureau Marketed Health Products Directorate Health Products and Food Branch Tel.: (613) Facsimile: (613) Regulatory Advertising Section Tel.: (613) Facsimile: (613) Web site Health Canada s Regulatory Requirements for Advertising: 46

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