Amid all the bluster and rhetoric surrounding the Patient Protection and Affordable Care Act of 2010, surprisingly little has been said about its stipulations to bring a certain type of generic drugs — known as “biosimilars” to the market faster and to make them more affordable.
Unless you are part of the biotech industry, chances are you don’t know that until February of this year, there was little regulatory guidance to assist in the development and approval of biosimilars. And chances are equally good that you have no idea what biosimilars are.
Biosimilars are, essentially, generic drugs. The difference is that the drugs companies are looking to replicate are not the over-the-counter sort. Medicines such as, say, ibuprofen, are considered chemical drugs. They are easily replicable and relatively simple to make.
The new FDA guidelines surrounding biosimilars refer to drugs with extremely complex protein-based formulations that are aimed at debilitating conditions. Drugs such as the anti-arthritic Humira and the lymphoma-fighting Rituxan. These headliners are known as “innovator drugs,” and they make major label manufacturers billions of dollars a year. And their patents are about to run out.
Expiring patents open the door for imitator drugs. The question is: How similar does a drug need to be for the innovator to be classified as a biosimilar? Michiel Ultee, the chief scientific officer at Laureate Biopharmaceutical Services at 201 College Road East, will address the issue of biosimilars and biobetters at the BioNJ Manufacturing Summit on Thursday, November 29, at 7:30 a.m. at the Hilton East Brunswick. Cost: $85. Visit www.bionj.org.
The question of how similar a drug must be to be considered a biosimilar is important because its action has to be similar enough to the innovator drug’s to be recognized as a viable alternative. To be called a biobetter, Ultee says, a new drug must be an improvement over an innovator. And that is its own ballgame.
Analyze this. When drug makers manufacture a new biologic for a major illness like cancer, they do so using a complex protein structure that involves combinations of the 20 amino acids and protein clusters of various sizes. The combinations, Ultee says, are plentiful.
These complex structures become very specific blueprints that are patented. In the 1970s, when Ultee first started working in immunology, protein drugs were serum-based. That is, the drugs were extracts from donor samples. By the 1990s technology had made it safer and easier to build drugs without serum extraction. It also made it easier for drug makers to patent their constructions.
But as original patented innovator drugs like Humira, Rituxan, and Remicade (which treats arthritis and Crohn’s disease) come off their patents, generics manufacturers are hoping to replicate these formulas. Patented or not, formulas are still protected insofar as you can’t simply make the exact compound. The trick, Ultee says, is to identify what makes a drug work without copying it too completely.
Heavy-duty analysis is important, Ultee says. Generics makers will have to subject innovator drugs to deep analysis, comparing and contrasting the innovators with their own versions. On top of that, the FDA’s new rules require clinical and laboratory studies to prove a drug maker’s versions of innovators are similar enough.
To make a biosimilar, Ultee says, requires looking at the fine structures of innovator drugs, testing multiple lots, and measuring the variances in the structures and results. Generics makers, after all, don’t have access to the innovator’s blueprints, so their efforts will always be of the drawing-board kind, he says.
This is better. But what happens when an imitator is very different from an innovator? Well, in short, it’s a whole different drug. Or, if it manages to isolate the thing that makes the innovator drug effective and then improves upon that aspect, it becomes a biobetter.
Ultee offers an example. Say part of an innovator drug binds to a cancer cell. A generics firm studies the drug, isolates that bond, and then finds a way to make the bond 10 times stronger. This could lead to a new treatment of the cancer — the more effective and stronger bond could mean lower-dosage pills or fewer doses.
There is, of course, an arms race. Major labels are, not surprisingly, aware that smaller labels are nipping at their heels as well as they are aware that innovation is the lifeblood of the life sciences. So major labels are working on second and third-generation drugs that could render the first-generation drugs obsolete.
The new frontier. Because the FDA’s guidelines on biosimilars only came out a few months ago, it is new territory for the bioscience industry, Ultee says. Based on what he knows and has seen in the industry since the mid-1970s, Ultee expects to see some distinct advantages for patients in need of major disease treatment. For one thing, he sees more availability and lower cost –– perhaps 50 percent.
He also sees more innovation from the big pharma manufacturers. Back in the 1990s, few were concerned with what would happen when the patents wore off, but with competition looking to get in on the action, even a small piece of the market can mean millions of dollars in lost revenue for major labels.
On the other side, Ultee foresees a lot of time and energy expended on the trial-and-error approach to making biosimilars. He also expects that a lot of attempted generics will not be similar enough and will, as a result, be unmarketable as alternatives. This, of course, would only serve to keep drug makers toiling away and keep alternatives off the market that much longer.
Ultee’s experience in the life sciences dates back to the early 1970s, when he first worked with antibodies at Dartmouth.
He graduated from Dartmouth with a bachelor’s in chemistry in 1973 before attending Northwestern for a master’s and Ph.D. in biochemistry. He then did postdoctoral work in immunology at New York University from 1980 to 1983.
Ultee was the director of manufacturing and technical operations at Cytogen Corporation, which developed antibodies and eventually became Laureate. He became Laureate’s chief scientific officer in 2010.
Ultee’s head for science, however, predates his college and professional life by decades. Born in the Netherlands, Ultee calls himself a third-generation scientist. His father and grandfather were both chemists in the Netherlands and his mother taught the subject. When Ultee was two, shortly following World War II, his father was transferred to the U.S. by DuPont.
As a boy, Ultee did what any budding chemist would do — he turned his basement into a laboratory for his experiments. Did he succeed in making anything? “Some good fireworks,” he says. “I ended up in the hospital for various explosions, but nothing serious.”
These days Ultee is not involved in many exploding labs, but he still loves chemistry and is deeply interested in where the new terrain of biosimilars and biobetters will go. “We’d been trying to figure out what the FDA wanted,” he says. “This is a little-known area. But we’ll see.”