Summer 2021 Edition - Biosimilars: Not the new kid on the block anymore

Biosimilars: Not the new kid on the block anymore

The last time Follow the Script^® brought you the topic of biosimilars was back in the winter 2018 issue when we described the successful pilot of the Green Shield Canada (GSC) Biosimilar Transition Program. Since then, there has been much advancement in the development of both biosimilar and biologic products and the conditions they treat.

But first, let’s review… What’s a biologic drug? Unlike traditional drugs, these products are produced through living cells or microorganisms (like bacteria) and are very complicated to develop and manufacture, making them extremely expensive. However, they provide treatment options for serious or rare illnesses where few, or no, effective treatments were previously available. So then, what’s a biosimilar? A biosimilar is a product highly similar to a specific originator biologic drug that is produced after the patent of the originator expires. Biosimilars can achieve the same positive health outcomes as originator biologics, but at significantly lower costs.

When we initially covered the topic of biosimilars (or subsequent-entry biologics) in 2014, they were relatively new on the scene with only a few available to treat a handful of conditions. Since then the list of biologics, biosimilars, and the conditions they treat has steadily grown; this includes new biologic treatments for common chronic conditions like asthma, eczema, high cholesterol, and migraines. The huge year-over-year growth in sales has resulted in biologic drugs becoming a major factor in growing drug plan costs. As this trend continues – and we see no signs that it will slow – it’s clear that biosimilars are key to keeping costs in line.

What is the difference in cost? Looking at a number of commonly used biologics and the corresponding biosimilars shows that the difference in prices ranges from 17 to 50 per cent. In 2018, Canada could have saved $807.7M had biosimilars been broadly adopted, but instead we saved only $93.9M due to dismal uptake. In other words, we only saved 12.2 per cent of what could have been saved.¹

In a climate of rapidly escalating drug costs for benefit plans, broad biosimilar adoption offers a clear and meaningful opportunity.

Solid evidence for switching to biosimilars

A particularly effective way to increase the use of biosimilars is for patients already being treated by an originator biologic to transition to the corresponding biosimilar product once it’s available.

We examined three systematic reviews that examined the results of a number of clinical trials that studied switching. All three reviews concluded that the available evidence showed that switching from an originator biologic to a biosimilar presented no additional safety risk or diminished efficacy:

• “Based on the currently available switch data of over 170 studies, there are no robust data that indicate that switching from a reference biological to a biosimilar is related to any major efficacy, safety, or immunogenicity issues.”²
  
  
• “Efficacy and safety data generally showed no differences between patients who switched treatments versus those who did not. No differences were seen pre- and post-switch.”³
  
  
• “The great majority of the publications did not report differences in immunogenicity, safety, or efficacy. The nature and intensity of safety signals reported after switching from reference medicines to biosimilars were the same as those already known from continued use of the reference medicines alone.”⁴

With the number of positive clinical studies growing as well as real world experience (including here in Canada – keep reading), switching has gained the support of various medical organizations including the Ontario Rheumatology Association, the Canadian Rheumatology Association, and the Crohn’s and Colitis Foundation in the U.S. As the evidence continues to accumulate, we expect the number of organizations in support of transitioning will continue to grow.

Bottom line: the major advantage in switching to biosimilars is that they result in the same positive health outcomes as originator biologics but at a much lower cost. As well, wider-spread use of biosimilars opens competition in the market so that more will be developed allowing even more access to these types of drugs.

The evolution of GSC’s biosimilar strategy

In April 2016, when biosimilars were fairly new on the scene, GSC launched what was then called the subsequent-entry biologic policy (now the Biosimilar New Start Program), which made biosimilars preferred products in our drug plans for patients newly prescribed the medication. In 2018, we developed the Biosimilar Transition Program in consultation with Arthritis Consumer Experts (a national patient-led organization). This optional program is designed to encourage the safe switching of specific originator biologics to appropriate biosimilar products. With new biosimilars regularly coming to market, we expanded the program to include new drugs in 2019 and again in 2021, and an additional expansion is planned later in 2021.

Since 2018, participation in GSC’s transition program continues to grow and savings for plan sponsors are adding up. An analysis of outcomes for rheumatic conditions revealed that, as of February 2021, 55 per cent of eligible plan members transitioned to a biosimilar while 14 per cent remained on the originator biologic, typically because they had coverage available through another plan. This meant that 69 per cent of these plan members were reimbursed the cost of the biosimilar. Of the remainder, 20 per cent had no further claims and seven per cent had a change in treatment. For this snapshot of plan members, their plans saw an average savings of $8,500 per plan member annually. With the upcoming expansion of the program to include Humira and the gastrointestinal indications for Remicade, these savings are only expected to grow.

A key feature of GSC’s Biosimilar Transition Program is case management support to ensure a positive plan member experience and to combat the possible “nocebo” effect – where a negative perception of therapy causes the treatment to have a poorer outcome than expected. So as part of our program, plan members are assigned a nurse case manager who provides them and their physician with educational and transitioning support.

In a recently published Canadian study,⁵ researchers examined patient perspectives both pre- and post-switch and found that patient support was a key factor in whether the switch was a success. Despite having knowledge about biosimilars and the upcoming policy change, there was still “apprehension and anxiety” among patients. But open communication, early notification, and adequate support, resulted in better patient satisfaction and maintenance of disease control post-switch. The study’s authors also concluded that “proper and effective communication strategies from health care providers to patients regarding the switch is integral to the success of their changeover and disease management.”

The provincial transition programs…

Since GSC’s program was introduced in 2018, a number of provincial transitioning programs have been launched. British Columbia was the first to launch a program with the Biosimilars Initiative in 2019 followed by Alberta in July 2020 and New Brunswick in April 2021. On May 18, 2021, the Government of Quebec announced its intention to implement a biosimilar switching policy and have provided some additional details since that announcement (visit https://www.quebec.ca/en/health/health-system-and-services/biosimilar-drugs). In addition to these four programs, Ontario approved a policy in February 2020 which wasn’t implemented due to the COVID-19 pandemic. But even without a program in Ontario as yet, the prevalence of transitioning programs across Canada is strong and growing.

GSC’s Biosimilar Transition Program – available in all provinces/territories (excluding Quebec at the time of publication)

• Transitioning is an optional program that plan sponsors can choose to implement
  
  
• Focus is on claimants where GSC is the primary payor
  
  
• GSC allows 90 days for transitioning
  
  
• After the 90 days, plan members can continue taking the originator biologic but the claim is paid at the cost of the corresponding biosimilar
  
  
• Nurse case management is offered to support plan members and their prescribers

How does the GSC Biosimilar Transition Program work in provinces with biosimilar initiatives – British Columbia, Alberta, New Brunswick?

• Transitioning is standard and is only applicable to claimants coordinating with government-sponsored drug plans
  
  
• Plan members need to transition by the deadline specified by the respective province
  
  
• No option for plan members to continue on the originator biologic (exception review process in place on case-by-case basis)
  
  
• GSC’s nurse case management isn’t offered; plan members and their prescribers are supported by the provincial biosimilar initiative

A strategy to handle biologics and biosimilars is needed now more than ever…

While the current list of drugs impacted by biosimilar transitioning programs is not a lengthy one, data from 2018 shows that six of the top ten biologic drugs by sales in Canada have a biosimilar available.⁸ Based on drug pipeline information, the remaining four can also expect to face biosimilar competition in the next three years. Adoption of biosimilar transitioning policies for this short but impactful list of biologic drugs presents a tremendous opportunity for drug plan sustainability, especially considering the growing number of new and costly biologic drugs entering the market and their expansion into the treatment of common chronic diseases. Now is the time to put a strategy in place and start taking advantage of the opportunity for savings.

Need more information?

Contact your account team for information on how GSC’s Biosimilar Transition Program can work for you. They can provide an eligibility analysis and the estimated cost savings based on your plan design and experience. They can also provide up-to-date information about the originator biologics and conditions included in the program. And be sure to listen to episode 31 of our podcast – “And now for something completely indifferent” – for more information on this topic!

Keep in mind – the sooner you implement the program, the sooner you start to reap the savings.

Sources

¹ Biologics in Canada. Part 2: Biosimilar Savings, 2018, Government of Canada website. Retrieved June 29, 2021: https://www.canada.ca/en/patented-medicine-prices-review/services/reports-studies/biologics-part2-biosimilar-savings2018.html.

² “The efficacy, safety, and immunogenicity of switching between reference biopharmaceuticals and biosimilars: A systematic review” (2020 study), Liese Barbier, Hans C. Ebbers, Paul Declerck, Steven Simoens, Arnold G. Vulto, Isabelle Huys; Clinical Pharmacology & Therapeutics. Retrieved June 22, 2021: https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.1836.

³ “Switching Between Reference Biologics and Biosimilars for the Treatment of Rheumatology, Gastroenterology, and Dermatology Inflammatory Conditions: Considerations for the Clinician” (2017), Robert Moots, Valderilio Azevedo, Javier L Coindreau, Thomas Dörner, Ehab Mahgoub, Eduardo Mysler, Morton Scheinberg, Lisa Marshall. Retrieved June 22, 2021: https://pubmed.ncbi.nlm.nih.gov/28623625/.

⁴ “Switching Reference Medicines to Biosimilars: A Systematic Literature Review of Clinical Outcomes” (2018), Hillel P Cohen, Andrew Blauvelt, Robert M Rifkin, Silvio Danese, Sameer B Gokhale, Gillian Woollett. Retrieved June 22, 2021: https://pubmed.ncbi.nlm.nih.gov/29500555/.

⁵ “Patient perspectives on the British Columbia Biosimilars Initiative: a qualitative descriptive study” (2021), Caitlin Chew,·Magda Aguiar, Nick Bansback, Michael R. Law, Mark Harrison, Rheumatology International. Retrieved June 23, 2021: https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC8102664&blobtype=pdf.

⁶ Biosimilars Initiative for Pharmacies, Government of British Columbia website. Retrieved June 22, 2021: https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/pharmacare/pharmacies/biosimilars-initiative-pharmacies.

⁷ “Webinar coverage: Switching to biosimilars can generate savings, say early adopters,” (April 7, 2021) Suzanne Lepage, Benefits Canada. Retrieved April 8, 2021: https://www.benefitscanada.com/benefits/health-benefits/webinar-coverage-switching-to-biosimilars-can-generate-savings-say-early-adopters/.

⁸ Biologics in Canada. Part 1: Market Trends, 2018, Table 2.1, Government of Canada website. Retrieved June 26, 2021: https://www.canada.ca/en/patented-medicine-prices-review/services/reports-studies/biologics-part1-market-trends.html.

Behind the counter

A controversial new drug for Alzheimer’s disease

A new treatment for Alzheimer’s disease was recently approved by the U.S. Food and Drug Administration (FDA) bringing hope to many patients. We talked to Ned Pojskic, GSC’s vice president, pharmacy benefits management, about the drug and the controversy.

FOLLOW THE SCRIPT: Ned, tell us about this new Alzheimer’s drug and why it’s a hot topic in the U.S.

Ned: This one is interesting. We’ve known about it for at least a year as it was going through clinical trials. The drug is called Aduhelm and the pharma company is Biogen. But first, the backstory is important on this. Alzheimer’s disease is a very common condition particularly among the elderly in Canada with over 70,000 individuals diagnosed each year. The cause of the disease is not known though it does have an association with age in that people over 65 are at-risk and the risk increases even more so at age 85 and older. The other thing is that the drug pipeline for Alzheimer’s is like a graveyard of failed attempts. There have been dozens and dozens of agents that have been tested through clinical trials over the years, all of which have failed to produce any meaningful effect on disease progression.

FTS: This is like a medical mystery in some ways.

Ned: In some ways, yes. The fundamental underlying principles of Alzheimer’s disease have now been revealed, and it has to do largely with the buildup of what’s called amyloid plaque. This slows the nerve impulses in the brain. You lose memories; you lose the ability to do the common daily tasks you were normally able do.

FTS: So they knew that amyloid plaque is the problem, but they couldn’t figure out what to do about it. Now this drug will reduce the plaque?

Ned: Basically. What it comes back to is a more fundamental problem of drug development, which is that you may know the general underlying causes of the disease, but if you get rid of some of those – in this case the amyloid plaque – does that mean you automatically change the course of disease? That’s the fundamental question for this particular drug.

FTS: OK, so that’s the challenge and that’s the disease state. Tell us about the drug and the FDA.

Ned: We have this drug – Aduhelm – that cleared some clinical trials. These broad clinical trials did not produce particularly exciting results, but Biogen observed some positive signals in the build up of plaque, though there were conflicting results in the two main clinical trials. The FDA approved the drug on the basis that potential benefits outweighed the risks, but it was a big controversy. The advisory group for the FDA that was tasked to review the data recommended to not approve Aduhelm, but the FDA went ahead and approved it anyway. Then three scientists resigned from the committee.

FTS: How often does that happen that the FDA would overrule an advisory committee?

Ned: It can happen; the FDA isn’t beholden to the recommendations of the advisory committees. That’s why they are “advisory.” Most commonly this sort of thing happens when it’s what’s called a breakthrough drug. There’s no other treatment so the regulator is willing to tolerate a lot more uncertainty and sometimes more safety signals. This often happens for cancer drugs, for example.

FTS: So ultimately Aduhelm has been judged to be safe enough that the FDA feels it’s not making things worse by letting people take it.

Ned: Well, that’s the other part of the controversy as it’s not innocuous. There’s a proportion of people in which Aduhelm causes some cerebral edema – that’s brain swelling – and in some cases, it causes microbleeds. This is an intravenous drug given every four weeks – it’s a serious regimen. And although it’s designed for early-stage Alzheimer’s, it’s very likely going to end up being used on a lot of other people. The pressure is going to be on from anyone and everyone desperate to try something where no other treatment exists.

FTS: Are the side-effects for Aduhelm happening more often than the side-effects we see for the COVID-19 vaccines, for instance?

Ned: Oh yes, absolutely. Up to 40 per cent of patients taking Aduhelm could suffer side-effects, so that’s a really significant safety signal. And then there’s uncertainty of whether it works. And now you have this issue which is more around the eligible population. Generally, agencies like the FDA and Health Canada tend to approve drugs for very broad indications; they don’t discriminate on the basis of the patients that were actually studied. They say “approved for Alzheimer’s.” We’ve seen that for other drugs. Then GSC, as a payor, struggles because we say how can we approve a drug when we don’t know whether it works for this patient? But then we and our plan sponsors get pressure to pay for it. So it’s a real problem of how regulatory agencies approve drugs more generally.

FTS: So this thing’s coming to Canada, and it’s going to be interesting for us. Is Health Canada more likely to see what you and other experts are saying – that this doesn’t make a lot of sense or is Aduhelm just going to get approved here too?

Ned: I’d say the latter. I do not see Health Canada coming in and saying we’re not approving this. Health Canada, like the FDA, has a bit of a track record lately of approving a lot of drugs with limited data through this breakthrough type of designation.

FTS: We should be pointing out that Aduhelm is a very expensive drug, right?

Ned: Yes, the United States pricing is $50K a year per patient. Canadian pricing is not known yet but it’s unlikely to be vastly different. And a lot of people are going to be taking it – in the U.S. the estimate is that up to one million Americans could access this drug.

FTS: What are some of the suggestions for health agencies and payors?

Ned: One thing that exists here, and certainly there’s importance in this body, is the Canadian Drug Agency, which combines Health Canada with CADTH [Canadian Agency for Drugs and Technologies in Health] with the pCPA [pan-Canadian Pharmaceutical Alliance]. That’s important because now you have the people evaluating drugs from a cost-effectiveness perspective sitting alongside people who approve them from clinical and safety perspectives, so presumably you might have a little bit more rigour into those approval decisions than you would with each agency acting independently.

FTS: With these experts coming together shouldn’t the logical result be not approving this drug?

Ned: Or, at the very least, requiring Biogen to further study the drug since the efficacy data is questionable. Health Canada has a mechanism called Notice of Compliance with Conditions (NOCc) at it’s disposal. The conditions can say something like Biogen can market the drug for now but has to study it further it for “X years” and report back.

FTS: To go back to the costs – what are some of the ways that we can at least mitigate the impact of this on overall health care budgets while still providing some level of access.

Ned: Now, I don’t know where our internal clinical review of this drug will land – the submissions have not been provided to us yet – but what may end up happening is some kind of managed access approach. Remember how we handled the hepatitis C drugs, where we first gave access to the sickest people, then over time we moved the boundary downwards to a broader population. Same thing with the COVID-19 vaccines. We allowed the elderly first and then opened access up to other groups.

FTS: Is that the only leverage payors will have? To step in and say it’s only for this population according to the research studies?

Ned: That’s one way. Another option is to procure Aduhelm nationally – like the way the COVID-19 vaccines were purchased by the federal government. They could set national targets on expenditures. They say to a company like Biogen, “we get it, we want to facilitate access, how about you get a $500 million dollars next year for whatever we need.” So we don’t see exploding costs due to utilization; everybody has access but there’s an absolute threshold on spending.

FTS: Thanks for filling us in on this drug, Ned. I’m sure we’ll be hearing a lot more about it.

Late-breaking news: Just before our editorial deadline, the FDA issued an update to its approval of Aduhelm that narrows its intended use. The FDA now recommends that the drug be limited to those with early symptoms of Alheimer’s or mild cognitive impairment. This will significantly reduce the number of patients eligible for the drug from six million to 1.5 million Americans. While the new recommendation doesn’t prevent Aduhelm from being prescribed to those with more advanced symptoms, Medicare and private insurers will likely restrict coverage to those with mild symptoms.