A Year Of Challenge For Teva And Copaxone

By Wayne Koberstein, Executive Editor, Life Science Leader
Follow Me On Twitter @WayneKoberstein

Almost since he joined Teva as CEO in 2012, Jeremy Levin has been under analyst and shareholder pressure on a number of fronts. A brief flare-up over company “secrecy” about his compensation faded after Teva revealed the details. But patent expirations looming for key products, primarily Copaxone (glatiramer acetate), have fueled concerns about whether the company’s development pipeline holds sufficient potential to replace the almost quarter of Teva’s revenue the product delivers. In the following excerpt from my recent interview with Levin, as in public statements, he barely hints at the company’s continuing search for an original product of Copaxone’s earning potential, offering no details; instead he emphasizes Teva’s promise to introduce at least 10 “new therapeutic entities” (NTEs) — existing drugs reengineered to enhance patient treatment and compliance — per year. (He outlines the details of that strategy in Life Science Leader October cover feature, “Teva Explores the Common Ground of Follow-On and Innovative Pharma.”) In the following, Levin answers some specific questions about Copaxone and the company’s pipeline. He also reveals much about how the company will defend the product from follow-ons, in addition to patent suits, with arguments based on its novel chemical structure and manufacturing process.

BECAUSE COPAXONE IS A COPOLYMER WHICH HAS A SEQUENCE THAT VARIES RANDOMLY (MAKING IT HARD TO CHARACTERIZE), IS IT PROTECTED FROM GENERIC COMPETITION?
LEVIN: Copaxone is extremely difficult to develop and manufacture and, as such, it is impossible for competitors to have fully characterized such a complex drug, even with the most sophisticated technology. Copaxone is so complex that no one, including the numerous experts Teva has consulted with, can fully characterize the drug or identify the active ingredient responsible for its efficacy.

Teva is able to produce Copaxone by exactly replicating its complicated manufacturing process, which has been supported by several clinical trials, to ensure every batch is identical, without variability. This process is proprietary and, therefore, competitors could not have produced a purported generic version that can be considered the same as Copaxone. Additionally, many patients tell us they would prefer to rely on the efficacy and safety of their current Copaxone therapy by converting to the 40 mg/ 1mL formulation, given three times weekly, which is currently pending approval in the U.S.

A COMPANY STATEMENT ARGUES THAT ANY GENERIC VERSION OF COPAXONE SHOULD GO THROUGH FULL CLINICAL TRIALS BECAUSE OF POSSIBLE IMMUNOGENIC EFFECTS AND INABILITY TO CHARACTERIZE THE RANDOM COPOLYMER CHAIN MOLECULE. ISN’T THIS THE SAME ARGUMENT ORIGINATOR BIOTECH COMPANIES USE AGAINST BIOSIMILARS OR, FOR THAT MATTER, PHARMA COMPANIES USE AGAINST MANY GENERICS?
With Copaxone, even minor changes to the composition of the treatment could have significant and unpredictable effects on the complex immunological mechanisms of the drug, raising major safety and efficacy concerns for patients. This is a very similar argument that is seen with biologics and it is this complexity that has led the FDA to consider clinical and immunogenic trials for biosimilars when chemistry is insufficient in characterizing the molecule. Knowing these products are highly immunogenic and that MS is a serious disease where one relapse can have lifelong effects, it is our position that patients will be at risk if these purported generic versions of Copaxone are not adequately tested via full scale, placebo controlled clinical trials with validated endpoints, such as relapse rate.

TECHNICAL POINT: IF THE COPOLYMER CHAIN IN COPAXONE IS RANDOM, WHAT IS THE STANDARD TO WHICH TEVA’S MANUFACTURED COMPOUND IS COMPARED, IN WHAT WAY IS ITS CONSISTENCY ENSURED, AND HOW ARE THE RESULTS OF TEVA’S PROCESS ANY MORE PREDICTABLE THAN THOSE OF MOMENTA’S METHOD?
As the originator of Copaxone, we have perfected the development process for this medicine by exactly replicating its complicated manufacturing process, which has been supported by several clinical trials, to ensure every batch is identical, without variability. This process is proprietary and, therefore, competitors could not have produced a purported generic version that can be considered the same as Copaxone. As such, it is our position that full scale, placebo controlled clinical trials should be required to ensure the safety and efficacy of any follow-on.

IT SEEMS THE ORIGINS OF COPAXONE WERE UNIQUE, INVOLVING AN EXCLUSIVE RELATIONSHIP WITH THE WEIZMANN INSTITUTE BEGINNING AT THE PRE-DISCOVERY STAGE. IS THERE ANYTHING NOWADAYS THAT COULD PRODUCE ANOTHER PRODUCT TO REPLACE COPAXONE AS A REVENUE OR PROFIT GENERATOR FOR THE COMPANY?
Teva will continue to focus on bringing innovative solutions to the market that provide value for patients and generate value for our shareholders. Copaxone will continue to be a viable alternative for people managing MS through the introduction of Copaxone 40 mg/1mL, given three times a week.

So there you have it — Teva’s strategy for dealing with a critical patent loss. There is some irony in a generics maker using a classic anti-generics argument to protect its blockbuster product. Sometimes, apparently, the common ground of originator and generics companies is common self-interest. Yet that alone is another sign of industry change, and it is a real situation that only adds momentum to the rapidly melding, formerly separate worlds of originator and follow-on pharma.

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