Tug of War: Biosimilars And Biologics Have Yet to Settle into Harmonious Coexistence
January 21, 2021
More than two decades after etanercept and infliximab launched the new era of biologic medicine, biologics are riding a seemingly endless wave.
They continue to expand their therapeutic reach, leaving prescribers with new polysyllabic names to learn every year, and dominate drug-spend in Canada. Between 2018 and 2019, expenditures for specialty medications (largely biologics) grew by 13.9%, compared to just 6.1% growth for non-specialty drugs,13 and the trend shows no signs of abating.
Since Canada approved the first biosimilar in 2009, these not-quite-generic drugs have offered a way to ease the cost crunch without compromising quality of care. That’s the theory, anyway. More than a decade in, biosimilar uptake remains dramatically lower in Canada than in many other OECD countries.14 Sales of Remicade, the originator infliximab brand and highest-earning biologic in Canada, continue to grow at an annual rate of about 2%,15 even though the drug now has four biosimilar versions. Whether deep-rooted prescribing habits, unclear coverage policies, or lack of prescribing incentives are to blame, the hesitation around biosimilars represents a missed opportunity.
None of this has prevented biosimilar development from forging ahead. All told, Health Canada has approved 31 biosimilars to date and has another 10 under review.1 Rituximab, a popular biologic developed in 2000, has seen three biosimilar versions enter the market in 2019 and 2020.1 Biosimilar action has also ramped up for bevacizumab, with the first biosimilar version appearing in 2018, the next one in 2019, and a further two in the approval queue.1
In the community setting, biologics and biosimilars for chronic conditions are fighting to claim their turf, while biosimilars for oncology have been tumbling into the hospital arena, creating unexpected decision points for public policymakers and hospital administrators. This feverish activity presents an opportunity to balance the market and inject savings into the system, while continuing to welcome innovator molecules that raise the treatment bar for patients. Here are some trends to watch for in this rapidly unfolding saga.
What's changing in the community setting
The big switch
Despite strong evidence that biosimilars perform as well as originators, Canadian physicians have been slow to embrace them. Canadian law generally requires physicians to place their patients’ best interests above cost containment,16 which could prompt more cautious physicians to keep stable patients on the originator molecule with the reasoning that what works doesn’t need fixing. By the same token, traditional listing policies may not have the muscle to change prescribing practices.15 Patients, for their part, may succumb to the well-known nocebo effect, whereby negative expectations of biosimilars dampen their clinical effect.17
That said, British Columbia’s Biosimilars Initiative is showing us what does work: mandatory switching policies. Launched in 2019, the program first focused on the blockbusters Enbrel, Remicade and Lantus, requiring patients using these drugs for specific indications to switch to their biosimilar equivalents over phased periods. To date, the initiative has led 78% of patients to make the switch,18 resulting in $97M savings19 that the province has reinvested in covering the drugs Jardiance and Taltz.20 The program has now turned its attention to switching patients on Rituxan to a biosimilar counterpart, a move that is expected to save the province at least 30% in treatment costs.18
Alberta is enacting a similar switching policy for several biologics, though the pandemic delayed its original rollout date, which is now set for January 15, 2021.21 Manitoba is taking a slightly different approach, with a tiered reimbursement policy that gives preference to cost-effective biologics and biosimilars and places restrictions on switching.22
Will Ontario and Quebec, the country’s most populous provinces, follow suit? The time appears ripe for a move: In Quebec, despite lowest-price policies, the originator biologic Remicade accounted for 91% of infliximab prescriptions,23 speaking to the need for more decisive action. An INESSS report has made a strong case for the safety of biosimilar switches, an effort that should reassure skittish prescribers.24
The stage is also set in Ontario, where only 16.7% of etanercept and infliximab users were treated with a biosimilar in the second quarter of 2019.25 The province did give the go-ahead to a switching policy in February 2020,26 though it has yet to announce a launch date or any details about the policy. Implementation cannot come soon enough: in the absence of a switch, an estimated 65% of patients on etanercept and infliximab will still be receiving the originator product by Q2-2022.27
The momentum is also building among private payers, though the uneven playing field may slow the pendulum’s arc.3 In late 2019, Pacific Blue Cross, British Columbia’s largest provider of extended health benefits, aligned its biologic coverage criteria with the province’s switching initiative. All but 1% of plan sponsors have opted into the new framework, to dramatic effect: between January and May 2020, biosimilars accounted for 68% of total infliximab claims, compared to just 23% over the same period in 2019.28 The change in etanercept biosimilar claims was still more pronounced—from 15% to 93%.28 Best of all, the transition allowed plan sponsors and members to avoid $22M in drug costs.28 Several other private payers have put similar programs in place, while others are following Green Shields Canada’s early lead with preferential listings for biosimilars.15
Molecule to watch: Adalimumab
The original adalimumab product, Humira, has proven itself a versatile molecule with an ever-expanding list of indications. With annual sales of $930M and 8.5% year-over-year growth, Humira generates more revenue in Canada than any other drug except Remicade.4 Not surprisingly, this standout performance has made adalimumab a prime target of biosimilar development. As it happens, several new adalimumab biosimilars are poised to enter the market in 2021—at more or less the same time.
While the molecule’s future looks rosy, the story of infliximab biosimilars—a story of missed savings opportunities for both public and private payers—could easily repeat itself with adalimumab. As the onslaught of adalimumab biosimilars draws near, stakeholders have the opportunity to do better. The community pharmacy and patient support programs (PSPs), in particular, are poised for meaningful change.
New roles for the community pharmacy
As this new wave of biosimilars approaches, the industry is quietly shifting gears. For a paradigm-disrupting development, we need look no further than the community pharmacy, where 73% of Canadians now access their biologic medications.15 And unlike infliximab, adalimumab comes in a prefilled syringe (PFS) formulation, which could mean more dispensing of biosimilar versions at community pharmacies.
While specialty pharmacies are here to stay and will continue to provide key services, Karine Matteau, head of biopharmaceuticals at Sandoz, sees an opportunity to “elevate the role of the pharmacist in the transition of thousands of patients to biosimilars.”15 This enhanced role could include nutritional counselling, side-effect management, and injection training certification.15 The day may even come when pharmacists have the authority to switch patients from one biosimilar to another—called biosimilar interchangeability—without involving a physician.
At the same time, it is easy to imagine the complications, at both the prescriber and pharmacy level, that the glut of adalimumab biosimilars could bring about. With so many biosimilars to choose from, doctors may settle into variable prescribing practices. Also, subtle differences in the ease of self-injecting the medication, like the size, shape or pressure of the injector, may swing patient preferences in unanticipated directions, which could feed back into prescription patterns. All this could make it challenging for community pharmacies to estimate demand and manage inventory, and for biologic manufacturers to size up their market opportunity.
PSPs in flux
A big part of biologics’ success depends on PSPs. Beyond handling such administrative tasks as reimbursement navigation, effective PSPs help promote treatment adherence and persistence, making them just as vital to biosimilars as to originator biologics. In fact, there is a PSP mandate for every biosimilar—and it’s not just a question of ticking a box. “As manufacturers of biosimilars, we are required by payers and provinces to prove we have a PSP that is equivalent to the originator,” Matteau explains.15
These high standards undoubtedly benefit patients. At the same time, the profusion of new market entrants could lead to a confusing quantity of PSPs. As a case in point, a single rheumatology website lists 21 PSPs, each with its own enrolment form29—and that’s not even counting the adalimumab biosimilars in line for approval. As Matteau points out, “if there are, say, seven PSPs for a pharmacist and physician to understand, how is that sustainable?”15
A suite of PSP solutions
Manufacturers and PSP vendors alike have been grappling with the challenge of maintaining a strong patient focus while keeping costs under control. Here’s what’s been happening and what we can anticipate with PSPs for biologics:- Variable range: Some PSPs have adopted a pared-down approach, focusing on the most essential services, while others are looking to differentiate through added value.
- Feedback loop: Forward-thinking PSPs are connecting more proactively with patients through simple tools such as surveys, using the feedback to improve their services.
- High tech: With Covid-19 having accelerated the need for contactless transactions, some PSP providers are ramping up the tech factor with such features as all-digital prior authorization.30
- New models – an area to watch: PSPs that cover a whole drug class or therapeutic area,31 proposed by some stakeholders as a way to create synergies and contain costs for all stakeholders, have yet to come to fruition.
Hospital Scene
Meanwhile, biosimilars used in oncology treatment have been making inroads into hospital settings. In one of the most undercelebrated biosimilar success stories, biosimilars for filgrastim—a drug that counteracts the low neutrophil count resulting from some oncology therapies—have to date captured more than 85% of the filgrastim market.6
More recently, the proliferation of biosimilar versions of oncology blockbusters rituximab, trastuzumab and bevacizumab has highlighted the need for guidance on introducing such medications to the hospital setting. To this end, a group called the pan-Canadian Oncology Biosimilars Initiative has been working to expedite and harmonize the uptake of oncology biosimilars.32 If Cancer Care Ontario (CCO) data is any indication, these efforts are paying off. As an example, treatments with bevacizumab biosimilars have climbed from zero to about 750 between August 2019 and August 2020, surpassing the figures for the reference biologic along the way.33 In BC, patients already taking the bevacizumab reference drug can continue to do so, though they also have the option of switching to the biosimilar version in consultation with their doctors.34
Handling multiples
How are multiple biosimilar entrants handled in the oncology space? The short answer: It depends. “It depends on the province, it depends on the jurisdiction, and different places have made different decisions,” says Helen Anderson of BC Cancer. Here are some of the factors at play:2
- Decision points: Some provinces make a top-down decision on which biosimilars to use, while others leave it to individual hospitals to make the decision.
- Short list: In Ontario, each hospital can select the biosimilars they want—as long as they’re funded by CCO. The government does not guarantee a market share to any new entrants.
- Fine points: Without consistent and transparent guidelines, decisions on which biosimilar is listed at the hospital may depend on such fine points as reconstitution time, level of foaming in the vial—or even size of the exterior packaging.
- Therapeutic inertia: In practice, hospitals often find it most convenient to stick with the first biosimilar they selected, posing a challenge to new market entrants.
In short: biosimilars have made great strides but have a lot further to go. BC’s Biosimilars Initiative, boasting thousands of successfully and safely treated patients, has forged a path that other jurisdictions can follow. Payers such as Blue Cross and Green Shield have demonstrated that biosimilar-first policies can work in the private sphere as well.
On the downside, uptake of biosimilars for major molecules continues to sputter, despite the requisite stakeholder consultations and body of reassuring data. Every day that goes by without biosimilar policies place represents millions of dollars in lost savings.
The opportunity to rein in biologic drug-spend and reinvest the savings into innovation and improved patient care lies within our grasp. What exactly are we waiting for?
References:
20Sense research. January 2021.
IQVIA report: 2019 top-50 products by total ethical purchases.
Specialty Pharma virtual summit, Session 5: the future of biosimilars in Canada. https://www.youtube.com/watch?v=bb43_JfBztA&feature=youtu.be
IQVIA report: Leading biologics by drugstore & hospital sales, 12 months ending June 2020.
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Pan-Canadian Oncology Biosimilars Summit. March 2019. https://www.cancercareontario.ca/sites/ccocancercare/files/assets/PanCanadianBiosimilarsSummitProceedingsReport_0.pdf
The Future of Biosimilars in Canada. Specialty Pharma Virtual Summit, September 2020. https://www.youtube.com/watch?v=bb43_JfBztA&feature=youtu.be
Murdoch B, Caulfield T. The Law and Ethics of Switching from Biologic to Biosimilar in Canada. JCAG 2020; 3:228.
Inserro A. Nocebo effect can hamper biosimilar acceptance, review says. AJMC. The Center for Biosimilars. Dec. 6, 2019. https://www.centerforbiosimilars.com/view/nocebo-effect-can-hamper-biosimilar-acceptance-review-says
Biosimilars initiative for pharmacies. British Columbia. https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/pharmacare/pharmacies/biosimilars-initiative-pharmacies
Hagen T. British Columbia Moves Into Third Phase of Mandatory Switching. AJMC. The Center for Biosimilars. August 25, 2020. https://www.centerforbiosimilars.com/view/british-columbia-moves-into-third-phase-of-mandatory-switching
B.C. expands use of biosimilars to offer coverage for more treatment options. BC Gov News, May 27, 2019. https://news.gov.bc.ca/releases/2019HLTH0080-001072
Notice – tiered biologics reimbursement policy. Effective August 15, 2018. Manitoba. https://www.gov.mb.ca/health/pharmacare/profdocs/notice_tiered_biologics.pdf
Provincial and territorial biologic policies. GI society. June 2020. https://badgut.org/information-centre/a-z-digestive-topics/provincial-biologics-policies/
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Safety of switching biologics and their interchangeability. INESSS. https://www.inesss.qc.ca/fileadmin/doc/INESSS/Rapports/Medicaments/CoupDoeil_switching_biologics_EN.pdf
Current and prospective utilization of innovator biologics and biosimilars in Ontario. ODPRN. January 2020. https://odprn.ca/wp-content/uploads/2020/01/Utilization-of-Innovator-Biologics-and-Biosimilars-in-Ontario.pdf
Ontario becomes third Canadian province to switch patients to biosimilars. GaBI Online. June 3, 2020. https://www.gabionline.net/Biosimilars/General/Ontario-becomes-third-Canadian-province-to-switch-patients-to-biosimilars
Utilization of Innovator Biologics and Biosimilars for Chronic Inflammatory Diseases in Canada: A Provincial Perspective. CADTH. January 2020. https://www.cadth.ca/sites/default/files/ou-tr/ho0007-biosimilars-utilization-final.pdf
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Patient support program enrolment forms. RheumInfo. https://rheuminfo.com/physician-tools/patient-support-program-enrolment-forms/#Truxima
Introducing Canada’s only electronic prior authorization. Telus Health. https://plus.telushealth.co/page/healthbenefits/epa/
The 20Sense Report, issue #11, January 23, 2020. https://www.20sense.ca/issue-11/2020/1/23/one-psp-challenge-four-big-ideas
Pan-Canadian Oncology Biosimilars Initiative Action Plan. March 2019. https://www.cancercareontario.ca/sites/ccocancercare/files/assets/PanCanadianOncologyBiosimilarsActionPlan_0.pdf
Reducing Uncertainty and Driving the Uptake of Biosimilars. Panel Discussion. 2020 CADTH Symposium.
Information and resources on biosimilar drugs for health care professionals. BC Cancer. http://www.bccancer.bc.ca/health-professionals/clinical-resources/biosimilar-drugs
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