Managed Care Pharmacists Survey: We’re on Board With Biosimilars, and Maybe Even Switching

Few suspected that payers were doubters of the clinical value of biosimilar agents, and as the first biosimilars were approved (2015-2016) managed care medical and pharmacy executives were somewhat reluctant to embrace them. However, within the past couple of years, managed care pharmacists told me these concerns were dissipating rapidly. (See the recent interview with Steven Avey as an example.)

A new survey on biosimilars released by the Academy of Managed Care Pharmacy (AMCP) confirmed that managed care pharmacists are on-board with biosimilar safety, efficacy, and the potential for switching. Conducted in October 2018, this survey offers solid evidence of the most recent thinking by pharmacy professionals on biosimilar access and promise.

Investigators from the Academy, PRIME Education, and the University of Pennsylvania analyzed the first 300 responses to their broad solicitation of AMCP members and associated professionals. Thirty-eight percent worked within a health plan or insurer setting, 22% in a pharmacy benefit management organization, and 40% in a specialty pharmacy.

The researchers stated, “84% agreed or strongly agreed that FDA-approved biosimilars are safe and effective for patients who switch from a reference biologic.” Although this does not specifically endorse switching to biosimilars from reference products, it does imply that the payers have no problem with the concept. They were still a bit wary of extrapolation of indications, however. A slight majority (54%) agreed or strongly agreed that extrapolation of indications for biosimilars was safe and effective.

The surveyed payers were asked to select the most effective strategies for increasing biosimilar utilization (i.e., overcoming barriers to biosimilar use). The responses rated the following strategies “extremely likely to be effective”:

  1. Clear FDA guidance for substituting reference biologics with lower-cost biosimilars that meet requirements for interchangeability (54%)
  2. Expanded Medicare and Medicaid policies that promote biosimilar use (41%)
  3. Educational programs for prescribers focusing on evidence from studies in which patients switched from reference biologics to biosimilars (39%)
  4. Formulary policies that promote biosimilar use for treatment-naive patients (39%)
  5. Educational programs for prescribers focusing on real-world evidence from postmarketing studies on biosimilars, including European studies (34%)
  6. Reduced cost sharing for patients using biosimilars (34%)
  7. Incentivizing providers by adjusting fee schedules for biosimilars (34%)

It should be noted that of the 16 potential strategies presented, only 2 (see below) did not garner more than 50% of respondents believing that they were at least “likely” to be effective.

In contrast, the strategies least likely to be effective were:

  1. Requiring therapeutic drug monitoring for patients who switch to biosimilars to address concerns about immunogenicity (28%)
  2. Incentivizing providers by using quotas for prescribing biosimilars to treatment-naïve patients (28%)
  3. Educational programs for prescribers focusing on streamlined billing, coding, and reimbursement processes for biosimilars (12%)
  4. Laws that promote greater public transparency on pricing of biosimilars and reference biologics (11%)

This survey does demonstrate that pharmacists’ comfort levels with biosimilars are fairly high. At the time of the study, it is likely that they had significant experience with only filgrastim and infliximab biosimilars (based on launch dates of the other approved agents, including epoetin and pegfilgrastim).

Challenges Extremely Difficult Difficult or Extremely Difficult
Concerns about biosimilar safety and efficacy among prescribers 16% 61%
Pricing and contracting issues 22% 57%
State laws for substitution and interchangeability 17% 53%
Concerns about biosimilar safety and efficacy among patients 13% 49%
Formulary management issues 8% 35%
Concerns about biosimilar safety and effiacy among payers 7% 23%
Data adapted from
https://www.jmcp.org/doi/full/10.18553/jmcp.2019.18412 .

In terms of these pharmacists’ opinions as to the most challenging barriers to biosimilar adoption, they rated as “extremely difficult”: pricing and contracting issues (22%), state substitution and interchangeability laws (17%), and prescriber concerns about efficacy and safety of biosimilars (16%).

When asked what biosimilar manufacturers can do, their responses emphasized pricing: Use contracting “to overcome the current [biologic reference] products’ substantial rebated dollars” and “come to market with more aggressive discounts off [average wholesale price].”

A Blueprint for Successful Infliximab Biosimilar Switching

Payers have not been quick to add biosimilar infliximab to their drug coverage. Yet, biosimilar switching is the objective for most health plans and insurers who are thinking about long-term savings. Even if they do not exclude the reference product Remicade® from coverage, some health plans, like Kaiser, have been moving forward in this effort.

At the Academy of Managed Care Pharmacy’s Nexus 2018 meeting in Orlando this week, two clinical pharmacy specialists from Kaiser Foundation Health Plan of the Northwest described what may be a best practice in converting patients to biosimilar Inflectra®.

RELEVANCE OF BIOSIMILAR SWITCHING AT THE PLAN LEVEL

Kayla Hubrich, PharmD, emphasized the importance of patient education, and patients’ reliance on Google for research. She said, “When patients will turn to Google and type in ‘Should I switch to an infliximab biosimilar?’ the first search result they see is an ad for ‘Finely Tuned,’ a Janssen website.” This, of course, discourages the use of biosimilars.

At Kaiser Foundation Health Plans, coverage decisions are made at a national level for its 12.5 million members and implemented at the regional plan level, according to Lynsey Smith, PharmD. The health plan made Zarxio® its preferred filgrastim product in 2016, and registered 96% of all filgrastim dispensings in self-injected settings, and 100% of all clinical administrations for this biosimilar.

Biosimilar switching
Source: Kaiser Foundation Health Plan

Obtaining that level of use means that not only treatment-naive patients were using Inflectra, but also those using Remicade in the past. Dr. Smith outlined the key steps in this conversion, starting with the providers. “For new starts,” said Dr. Smith, “the tactic was just to have the doctor choose the biosimilar” using tools incorporated into the electronic health record that encouraged them to order the preferred product. Concerning those patients needing to be converted from the reference product, Kaiser asked the prescriber to sign a ‘Therapeutic Equivalency Protocol’ agreement, which authorized the plan to make the switch. The biosimilar switching agreement was voluntary, and virtually all the rheumatologists, dermatologists, and gastroenterologists signed. “One GI out of 20 declined to authorize the switch in patients already receiving Remicade,” she said.

Kaiser emphasized patient notification and education. A letter, signed in their doctor’s name, was sent to each patient at least 2 weeks before the conversion date, explained Dr. Smith. Clinical Pharmacy Services was enlisted to answer patients’ questions via phone and E-mail. Patients were also given informational handouts about the biosimilar switching program at their infusion center.

“During this process, the clinical pharmacists received 30 to 40 calls,” she said. “The patients’ main concerns were whether the product was going to work as well as their old drug and whether they would receive the same copay assistance as before.” Active patient outreach was not conducted after the switch was instituted. Any patients reporting issues or concerns were triaged through Clinical Pharmacy Services.

Dr. Hubrich added that infusion center pharmacists reviewed all patients scheduled for infusions one week ahead of their appointment. The infusion center confirmed that the provider signed a TEP document, that patients were sent the notification letter, and that the infliximab order changed to Inflectra. Kaiser also developed a nurses’ protocol for the biosimilar switch and worked to educate practice staff about the program.

 

INFLIXIMAB SWITCHING PROGRAM RESULTS

The conversation program began on May 1, 2017, with dermatologists and rheumatologists, focusing on patients who were getting their first infliximab treatment. Dr. Hubrich stated that notification letters were sent to 158 patients. Three weeks later, current patients began to be switched from Remicade to Inflectra. The GI conversion began on May 11, 2017 with treatment-naïve patients, and letters were sent to 188 adult patients (as Inflectra did not have the pediatric ulcerative colitis indication). Active therapeutic switching began in September. “The one GI who declined to sign the TEP agreement joined in 2018,” said Dr. Hubrich. This is likely because of the experience of this doctor’s peers.

A total of 22 patients (6.4%) across specialties reported adverse events, with nine being changed back to reference product (2.6%), five changed to a different medication class, four resulted in a dosage increase, one patient decided to discontinue therapy, and three continuing biosimilar infliximab treatment without any change. They did find that 12.8% of patients experienced some “nocebo” effects, despite the fact that “no statistically significant changes in effectiveness and safety were observed after a medican of four infusions in 9 months of study.”

Dr. Smith asserted that communication was critical to the success of the program, with patients and providers. The provider’s agreement to sign the TEP document was a necessary step, and was accepted by all Kaiser’s specialist providers.

It must be emphasized that Kaiser has a different magnitude of leverage over its physicians than a network plan like Aetna or CIGNA. Yet a biosimilar switching program like this could be a blueprint for other integrated health plans to move forward if they desire to move patients quickly and efficiently to biosimilar therapy.

More Clinical Study Evidence That Biosimilar Switching Carries a Low Risk

A literature review published this past weekend in Drugs reaffirms what most parties interested in biosimilars suspect—that switching from a reference product to biosimilar is not a significant clinical concern. Biosimilar switching was not generally associated with poorer outcomes.

The study evaluated the results of 90 clinical studies comprising more than 14,000 patients with 14 diseases or conditions. The authors from Novartis (and its Sandoz subsidiary), the Oregon Medical Research Center, Rocky Mountain Cancer Centers, IBD Center of Humanitas Clinical and Research Hospital (Milan), and Avalere Health stated that “the great majority of the publications did not report differences in immunogenicity, safety, or efficacy [as a result of biosimilar switching]. 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.” In addition, they reported, “Three large multiple switch studies with different biosimilars did not show differences in efficacy or safety after multiple switches between reference medicine and biosimilar.”

In this evaluation, the biosimilars tested included those for infliximab, epoetin, filgrastim, growth hormone (which has not been considered a biosimilar in the Ubiosimilar switchingS), etanercept, and adalimumab. Infliximab was the subject of the majority of the clinical studies.

Of the 90 studies, two were outliers, suggesting potential safety issues associated with biosimilar switching. One was described as a 2016 retrospective study of a claims database from Turkey, which found a much higher discontinuation rate with the infliximab biosimilar compared with originator product in patients with rheumatoid arthritis.

The authors correctly note that the vast majority of the studies reviewed involved a single biosimilar switch, and that multiple switches may result in additional safety signals. However, they also point out that “patients have already been exposed to de facto multiple switches for many originator biologics when product quality attributes changed after one or more manufacturing process modifications were introduced.”

The question arises as to whether multiple switch studies are truly necessary outside of the requirement to prove interchangeability between a biosimilar and a reference product. There is a practical reason for doing so—the possibility (actually, the likelihood) of a patient enrolling in a new health plan one year, which covers the biosimilar but not the reference product. If the patient’s health plan changes once again one or two years later, that person may well be required to switch back to the reference product or yet another biosimilar.

This will heighten the importance of collecting real-world evidence and accumulating more experience outside of the clinical trial environment in terms of switching. Efforts such as those at the Biologics and Biosimilars Collective Intelligence Consortium should fill this gap over the next several years.