Momenta Pharmaceuticals, Inc. (MNTA)

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Momenta Pharmaceuticals: How To Unlock The "Black Box" Of Biosimilars
By Anna Rose Welch, Editor, Biosimilar Development November 24, 2015

Excerpts:

Wheeler acknowledges there will be more products landing on the market and more defined guidelines from the FDA in 2016, he says “I don’t see any big revolutions out there next year, but I do see further evolution and refinement of the pathway.”

Wheeler says,“The reality of the situation is, once biosimilars get into the marketplace, they’re going to be used because the payer strength and the pressures on cost are so high in the U.S.”

Momenta, which was one of 30 companies borne from a lab at MIT, was built to challenge the notion that complex drugs (including biologics) were a “black box” filled with inexplicable structures and incomprehensible variabilities. “We could develop the tools to understand everything that is in these biologics. There’s no mystery at all if you have the right lens to look at it,” says Wheeler.

This is why the company has been concerned with making the appropriate technology investments that will enable it to design biosimilars that boast “fingerprint-like” similarity, and, in turn, make the development process more efficient. In order to ensure that the FDA’s pathway will be accepting of the company’s technology, Wheeler says the company is aggressively preparing for the upcoming Biosimilar User Fee Act (BsUFA) negotiations. These negotiations will be key to determining whether the company will be able to “use the technology and science that we have to abbreviate the necessary trials and efficiently obtain extrapolation and interchangeability,” Wheeler says.

On the scientific front, Wheeler says the biggest challenge is determining how to choose and manipulate the cell lines. In the small molecule realm, the manufacturer is faced with controlling four or five variables, including time, temperature, pressure, concentration of reactions, and potentially catalysts. However, when working with cells, there can be anywhere from 100 to 300 variables impacting the formation of the necessary protein. To be able to gain more control over these variables, Wheeler describes how, “We started mapping out the entire genetic machinery that mammalian cells use to assemble proteins in order to understand how to select the cells that have the right machinery to bring the attributes we want in the product. This process also enables us to have much more control over manufacturing, which is necessary to make products that are much, much closer to the brand than you would typically get using a more traditional biologic development process.”
Figuring out how to overcome these challenges is a point of pride for Momenta. In fact, Wheeler argues that the investments and process design for a biosimilar are much more difficult than creating a new drug. He says, “We put significant investments into understanding the genetics of the cells and then trying to design a process to actually control manufacturing more carefully than we would in developing a novel drug, because it’s harder to make a duplicate than it is to make an original.” While establishing the same gene structure/protein backbone is the ultimate goal, there are still a number of different and complicated factors a biosimilar developer needs to maintain control over. These factors include glycosylation, crosslinking, polymorphism, and contaminants (in particular, host cell proteins and truncated molecules), among others. To do all this, Wheeler says, “Requires a combination of advanced analytics and a highly developed process control.”

While a biosimilar is an imitation of a reference product, it’s still important to acknowledge that the process of creating one requires just as much innovative science as an original molecule — and it’s clear that this is exactly how Momenta views the process. As Wheeler says, “We have prided ourselves on being innovative on the science that we’re bringing to the FDA on every product we’ve done so far, and we expect to continue that in biosimilars.”

http://www.biosimilardevelopment.com/doc/momenta-pharmaceuticals-how-to-unlock-the-black-box-of-biosimilars-0001