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Pink Sheet – Biosimilar Prescribing Decisions May Depend Upon Disease State

Pink Sheet – Biosimilar Prescribing Decisions May Depend Upon Disease State

Executive Summary

Express Scripts’ Eichholz says clinicians may be less inclined to use a biosimilar in ‘life or death’ oncology indications compared to inflammatory diseases.


Clinical decisions on whether to prescribe a novel biologic or a biosimilar may be driven, in part, by the condition and stage of disease, representatives from the pharmacy benefit, patient and clinician communities say.


“In terms of interchangeability, substitutability, similarity, it could very well depend upon the disease state,” said Jeff Eichholz, senior director of drug trend solutions at Express Scripts Holding Co., at an Oct. 18 meeting on the future of the US biosimilars market, co-sponsored by Friends of Cancer Research and the Duke-Robert J Margolis Center for Health Policy.


In discussing how biosimilars will be viewed and used in the clinical setting, Eichholz drew a distinction between oncology and inflammatory conditions. Physicians might be more inclined to use a biosimilar for inflammatory conditions than in oncology, “where you are literally talking life or death,” he said.


Although the US market has seen only one biosimilar to date – Sandoz Inc.’s Zarxio (filgrastim-sndz), a biosimilar to Amgen Inc.’s Neupogen (filgrastim) – three others have been licensed by FDA. One of these, Celltrion Inc.’s Inflectra (infliximab-dyyb), which references Janssen Biotech Inc.’s Remicade (infliximab), will be launched in late November by Pfizer Inc. (Also see “How Risky Is Pfizer’s Launch Of Its Remicade Biosimilar?” – Pink Sheet, 18 Oct, 2016.)

Should Interchangeability Be Required In Oncology?

As more products move through the approval process and reach the cusp of commercialization, there is growing anxiety in the patient and clinician communities about how biosimilars will be incorporated into treatment paradigms.


Much attention has been focused on the importance of, and uncertainty about, physician confidence in the emerging class of products. In addition, patient advocates have been highly vocal in expressing concerns about the potential for non-medical switching, whereby individuals are moved from novel biologics to new biosimilars due to financially driven coverage decisions. (Also see “Biosimilar Non-Medical Switching: Advocacy Groups, FDA Advisors Push For Action” – Pink Sheet, 14 Jul, 2016.)


For example, patient advocates often point to the decisions by CVS Health Corp. and UnitedHealthCare to include Zarxio but not Neupogen on their standard formularies for 2017. (Also see “Rise Of The Biosimilar Formulary: CVS Excludes Lantus, Neupogen For 2017” – Pink Sheet, 2 Aug, 2016.) (Also see “UnitedHealthcare Prefers Basaglar Biosimilar At Lantus’ Expense” – Scrip, 22 Sep, 2016.)


In terms of biosimilar prescribing and clinical decision-making, Eichholz’s distinction between cancer and inflammatory diseases found support from Andrea Ferris, president and chairman of the lung cancer advocacy group LUNGevity.

“I think that maybe oncology or a disease like cancer needs to have more stringent requirements.” – LUNGevity’s Andrea Ferris

“Is it different for oncology versus other longer term diseases? I think that maybe oncology or a disease like cancer needs to have more stringent requirements,” Ferris said.


Under the Biologics Price Competition and Innovation Act (BPCIA), a, biosimilar must be demonstrated to be highly similar to the reference product with no clinically meaningful differences. Ferris, however, suggested this standard may not be enough in an oncology setting, and that there should be a requirement for interchangeability.


BPCIA defines an interchangeable biosimilar as one that can be expected to produce the same clinical result as the reference product in any given patient and that, for a product administered more than once, the risk in terms of safety or diminished efficacy of alternating or switching between the biosimilar and the reference product is not greater than the risk of using the reference product alone.


FDA has yet to issue guidance on interchangeability. Although FDA’s commitment under the Biosimilar User Fee Act II agreement with industry calls for the guidance to be released by Dec. 31, 2017, agency officials continue to hope that such guidance will issue this year. (Also see “Biosimilar Guidance Development Timelines Criticized By Docs And Patients” – Pink Sheet, 20 Oct, 2016.)


“Maybe we do have to have a requirement for interchangeability because if you’re in a community setting, you’re not going to look at whether its biosimilar or interchangeable, you’re just going to assume that it’s interchangeable, and it might have dire consequences for the patient,” Ferris said. “Perhaps in disease states like that where it’s a more intense or high-risk situation, we might need different levels of standards for biosimilar approval or reimbursement.”

Inflammatory Diseases Also Life-Threatening

Not surprisingly, the distinction between biosimilar prescribing for cancer and inflammatory diseases drew some pushback.


Speaking from the audience, Kathleen Arntsen, president and CEO of the Lupus and Allied Diseases Association, said she has multiple autoimmune conditions, takes over 40 drugs a day and has almost died twice due to medication changes.


“Even though I have inflammatory disease, those diseases are life-threatening, too” she said. “It’s just as important to our population that we be not switched, or have clinical considerations taken into account and not have our treatments changed based on cost.”

“To date we have not received the clinical guidance to impact a patient who is currently on therapy, even though going forward new starts and new diagnoses may be shifted to a particular product.” – Express Scripts’ Jeff Eichholz

Responding to Arntsen’s comments, Eichholz noted there are different considerations with regard to management strategies for new patients versus those currently on treatment.


“I can tell you right now, sitting here looking at the biosimilar products, as an organization to date we have not received the clinical guidance to impact a patient who is currently on therapy, even though going forward new starts and new diagnoses may be shifted to a particular product,” Eichholz said. “That is a difference that I think is a detail of a difference but often gets lost in the general overarching conversation.”

Disease Stage Also A Factor

Richard Schilsky, senior vice president and chief medical officer of the American Society of Clinical Oncology, predicted that whether a patient is started on a biosimilar or switched to one will depend a lot on the current state of the disease.


For “newly diagnosed cancer patients who get a biological drug as part of their therapy, it’s a different decision to make in terms of which drug you start the therapy with, versus someone who’s had their cancer under control for a year or more perhaps with a brand name product, and then you might want to switch to the biosimilar,” Schilsky said.”


In addition, there are “complicated issues in cancer in the interplay between management decisions and biology,” Schilsky said, describing how tumors develop resistance to therapeutic agents.

He questioned whether it would be possible to assess a biosimilar’s effectiveness in clinical practice.

“It will be very difficult to determine subtle differences in the efficacy” between the biosimilar and reference product. – ASCO’s Richard Schilsky

“I think the differences in safety profile are likely to be small, they may be primarily in the realm of immunogenicity, but I don’t think it will be difficult to sort out safety events,” Schilsky said.


“What I’m much more concerned about is that it will be very difficult to determine subtle differences in the efficacy,” he said. “In every population of cancer patients, there are some treatments that just don’t work, even though the drug globally is clearly a safe and effective drug. So if you start substituting biosimilars, and they don’t seem to be working in your patient, what are you supposed to conclude? Is that because there’s a problem with the drug? … Is that because the tumor has some intrinsic resistance to that whole class of drugs that even the originator drug wouldn’t have worked in that patient?”


“Sorting that out over the long term I think is going to be extremely challenging for us,” Schilsky said.…