Tag: extrapolation

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].”

Would Biosimilar Approvals With Limited Indications Alter the IP Discussion?

Over the next couple of weeks, I’ll be issuing a series of posts to further analyze some of the Food and Drug Administration’s (FDA’s) new Biosimilars Action Plan.

The Biosimilars Action Plan contains several important components. One of the more interesting items FDA Commissioner Scott Gottlieb mentioned in his remarks at the Brookings Institution webinar on Wednesday, July 18, involved modifying the intellectual property (IP) discussion with biosimilar approval for limited indications.

Originator drug makers have erected a so-called patent maze or patent wall over time to protect their IP and thus their marketing exclusivity as far into the future as possible. Patents can be filed for product composition, manufacturing techniques, new formulations, delivery systems, and indications. Often, the biologic products facing potential biosimilar competition have several indications. Adalimumab, for instance, is approved for use in nine unique conditions (I’ve included Crohn’s disease and pediatric Crohn’s as one disease state).

Dr. Gottlieb said that the FDA will be “updating guidance to provide additional clarity on how biosimilar manufacturers can carve out indications from their labels where a branded drug maker might still maintain some IP.” He continued, “And we’re going to describe how these indications can be efficiently added into a biosimilar label once that IP on the branded alternative has lapsed.”

This component was not spelled out in the Biosimilars Action Plan. Limited indications may indeed be an avenue to work with originator manufacturers to help reduce patent litigation that is barring patient access to biosimilars. One would assume that it would take some level of negotiation with the manufacturer of the originator. However, biosimilars with limited indications may be a hornets’ nest for reference manufacturers like AbbVie.

This gets back to the entire issue of extrapolation. From the outset, patients and providers recoiled at the notion of approving a biosimilar product for use in a disease state in which no clinical studies were done. The FDA has been pretty liberal in granting extrapolation to several or all indications for the 11 approved biosimilars. If FDA explored this option as a mechanism for getting biosimilars to the market sooner, it would be sending a new message. That is, the biosimilar drug may be expected to yield similar outcomes compared with the reference drug based on the totality of the evidence, but we’re unwilling for other reasons to give it our approval for those other indications.

Biosimilar Indications Laws or regulations do not exit to prevent doctors from prescribing a biosimilar for a nonapproved indication. Furthermore, health plans and insurers have consistently reported in our own market research that they would not discourage use of a biosimilar for other indications for which only the originator biologic was approved. This assumes the biosimilar is sufficiently less expensive than the originator. As a result, drug makers like AbbVie may be very wary of the limited-indication approach to improve biosimilar access.

Still, some way must be found to break the logjam of litigation on IP. This is a specific target of Commissioner Gottlieb’s. He may take even more creative approaches.

 

 

 

 

 

 

Restating the Record on Biosimilar Safety and Efficacy

At this point in time, it may be a bit more difficult to find professionals who are convinced that approved biosimilars are not as safe and effective as the originator agents. The call of those manufacturers defending their long-time marketshare is being drowned out by (1) informational sites published by major pharmaceutical manufacturers and marketers, and (2) the facts presented by the governmental agency with the most experience approving and regulating biosimilars—the European Medicines Agency (EMA).

Several manufacturers have excellent resource sites on how biosimilars are manufactured and how they differ from the originator products. These include “minor” players such as Amgen, Merck, Pfizer, among others. Their sites are pretty informative, and do not seem to be developed strictly as a marketing platform for their biosimilar products. As a group of resources, they are contributing to a public educational effort to ease potential concerns with biosimilars.

The immunogenicity and extrapolation issues are historically the greatest points of sensitivity to patients and providers. The EMA issued a report in May 2017 that summarized its findings over 10 years of biosimilar surveillance—there is no evidence of safety problems or efficacy problems with approved biosimilar products since the first licensed product. “Extrapolation is not a new concept but a well-established scientific principle used routinely when biological medicines with several approved indications undergo major changes to their manufacturing process (e.g. to introduce a new formulation). In most of these cases, clinical trials are not repeated for all indications and changes are approved based on quality and in vitro comparability studies,” states the report. Moreover, “Over the last 10 years, the EU monitoring system for safety concerns has not identified any relevant difference in the nature, severity or frequency of adverse effects between biosimilars and their reference medicines.”

Although this is absolutely true for the first-generation of biosimilars, the monoclonal antibody biosimilars have been licensed by the EMA more recently, with the first being infliximab in 2013 and the last being rituximab and etanercept in June 2017. Over time, utilization and evidence will accumulate to support their safety and effectiveness in real-world practice and across multiple indications. Yet, the potential for immunogenicity, which several switching studies have shown is low, will eventually fade as a concern.

The “Eprex Incident” of 1998 remains the sole alarm bell for a true product safety problem related to the manufacture of a biosimilar-type of product (predating by several years the introduction of biosimilars and biosimilar approval regulations, even in Europe).

Obviously, the past does not predict the future. That is one reason why organized surveillance efforts are needed both in the EU and in the US to capture any safety signals. However, it does seem that products making it through the regulatory approval systems are delivering the promised results.