Copaxone through the years
After a group of scientists—Michael Sela, Ruth Arnon, and Dvora Teitelbaum—at the Weizmann Institute of Science in Rehovot,
Israel, discovered copolymer 1, which would become Copaxone, they shopped it around to several large pharmaceutical companies.
All of them declined; no innovative brand drug discovered and developed in Israel had ever been approved by FDA. Copaxone
would become the first.
At the time, Teva produced generic medications exclusively, but Sela, from the original discovery team, was friends with Teva's
founder and CEO, Eli Hurvitz. Sela and his wife Sara invited Hurvitz and his wife Dalia over to dinner. Sela arranged for
a slide projector and screen, and the two couples reviewed data from the previous 17 years of copolymer 1 development. Intrigued,
Hurvitz negotiated Teva's rights to the product with the Weizmann Institute, according to Teva.
Copaxone launched in the US in 1997 (and across Europe in 2001) but wasn't terribly convenient for patients. It was a frozen
lyophilized product that required reconstitution before a traditional injection. The initial peak sales forecast was $250
million, according to Derkacz. In 2000, the Autoject device was introduced, making it much easier for patients to use. The
same year, Copaxone jumped past Bayer's Betaseron to become the second most frequently used MS therapy. In 2002, prefilled
syringes were brought to market, which again made administration easier for patients. By 2008, after Biogen Idec's Tysabri
had been pulled from and then put back onto the market, Copaxone had become the market leader by prescription volume and demand.
When Novartis's Gilenya (2010), and then Biogen's Tecfidera (2013) hit the market, it was supposed to be curtains for Copaxone.
"The reality is while they've gotten some traction, things haven't really changed a lot for Copaxone," says Derkacz. "We've
been able to maintain prescription volumes for the most part, though 2013. And it really set the stage nicely for the launch
Generics coming this month?
In January, a Teva-sponsored study published in PLOS ONE aimed to show a difference between Copaxone and a "purported generic"
in development. In a release on the study, co-author Michael Hayden, president of global R&D and chief scientific officer
for Teva, said the "data from this paper shows the possible significant ramifications of changes in physiochemical properties
between Copaxone and a purported generic." He went on to say the study "suggests a distinct potential difference in the impact
of a purported generic on the immune system of patients, with possible implications on efficacy and safety in relapse-remitting
MS patients. Teva believes the only way to truly understand the impact of these differences is by conducting a full battery
of clinical studies."
The active ingredient in Copaxone is a mixture of polypeptides containing a huge number of active amino acid sequences which
can't be "accurately characterized using state of the art analytical techniques," says Hassler. "The only way to demonstrate
efficacy, safety, and no differences in immunogenicity, is through well-controlled, comparative clinical trials."
It's unclear whether FDA will be sympathetic to this view. Craig Wheeler, CEO of Momenta, one of the lead developers of generic
Copaxone, certainly is not. He says Teva is trying to "throw wrenches" into the FDA review process. Wheeler says he wouldn't
give Teva his product for research, and doubts Mylan would have either, meaning the generic drug evaluated by Teva must have
come from somewhere outside the US.
As for gene expression and the contents of the Teva study, Wheeler says "it's nice to put a big color graph in front of investors,
but it doesn't really hold a lot of scientific water." Why not? "If you look at gene expression and how it works, it can vary
animal to animal, it can vary by time of day, it can vary temporally," says Wheeler. "If you applied statistics to the data
they've shown, you would have a hard time showing that there's any statistical significance in what they're saying."
Teva agrees to disagree, but the possibility of a generic 20mg Copaxone approval is one the company is nevertheless prepared
for, says Hassler. "We'll continue to build brand loyalty, and at the end of this I believe most physicians and patients as
well as many payers will opt for a clinically proven therapy."