A New Class of Medicines: Biosimilars Are Coming
You’re probably familiar with generic medicines, which are less expensive copies of brand-name medicines. For headache relief, you can buy a brand-name product such as Tylenol or its generic, acetaminophen. There are even generics for some breast cancer medicines: if you have hormone receptor-positive disease, for example, you might take a generic instead of a brand-name aromatase inhibitor.
But some medicines can’t be copied exactly, so generic versions can’t be made. Scientists are working to change that. Biosimilars are copies of biologics, medicines made from living cells rather than chemicals. These cells might come from an animal, plant, bacteria or other microbe. In breast cancer, one of the best-known biologics is trastuzumab (Herceptin), which is an antibody originally produced in mouse cells and used to treat HER2-positive breast cancer. This antibody targets the protein HER2 on the surface of breast cancer cells, stopping it from spurring on cancer growth.
Biosimilars are hard to make: Living cells are more complex than chemicals to recreate, and they can’t be copied exactly as chemicals can. It’s happening, though — and, like generics, biosimilars are intended to be less expensive than brand-name biologics. New biosimilars for breast cancer treatment should start rolling out in 2019, giving people with certain types of breast cancer more options and helping them save on costs.
What Are Biosimilars?
Think about your favorite brand of bottled drink, such as soda or iced tea. It tastes reliably the same every time since the formula doesn’t change. It’s different when you’re ordering a glass of wine, such as cabernet or chardonnay. You know basically what that type of wine will taste like, but there will be some variation each time. The winery’s growing conditions, location, and process can all affect the final result.
This is one way to understand the difference between generics and biosimilars. A generic medicine uses the same active ingredients and chemical structure as the brand-name version. But manufacturers cannot copy a biologic medicine exactly because the living cells they use constantly change. That’s why the copies are called biosimilars: They’re similar enough to the original medicine to work equally well.
“Copying a biologic is more difficult because of the way they are made, using living material,” says Alison Stopeck, MD, a medical oncologist and breast cancer specialist at Stony Brook Medicine in New York. “Even with an original brand-name biologic, like Herceptin, there can be very small differences from batch to batch. I don’t think people always realize that.”
The U.S. Food and Drug Administration requires a biosimilar to go through a rigorous testing process before it can be re-searched in humans. Then it has to be compared to the original biologic in people. The studies must show that the biosimilar gives a similar result in treating the condition, with similar safety and side effects.
Biosimilars in Breast Cancer
- Trastuzumab-dkst (Ogivri), biosimilar of trastuzumab (Herceptin), approved in December 2017 to treat HER2-positive breast cancer but not yet available to the public
- Filgrastim-sndz (Zarxio), biosimilar of filgrastim (Neupogen)
- Pegfilgrastim-jmdb (Fulphila), biosimilar of pegfilgrastim (Neulasta)
Each biosimilar’s trade name includes the name of the original medicine (such as “filgrastim”), along with a four-letter code unique to each manufacturer (“sndz” in “filgrastim-sndz,” above). This way, as more versions of the same medicine come into use, it will be easier to identify which version of the medicine is being used.
How Do I Get A Biosimilar?
Despite FDA approval for some biosimilars, their use in breast cancer care has been slow-growing.
How quickly trastuzumab-dkst will come into use remains to be seen. Genentech, maker of Herceptin, holds a patent that doesn’t expire in the U.S. until 2019. Patents allow companies to be the sole maker of a product for a set amount of time. Researchers are testing other biosimilars of trastuzumab in the meantime, such as CT-P6 and SB3.
Whether you’ll be treated with a biosimilar will probably depend on what health insurance companies decide, says Douglas Yee, MD, breast cancer specialist and director of the Masonic Cancer Center, University of Minnesota. Like generics, biosimilars will likely cost less than the brand-name medications, which should make them appealing to insurers.
“In clinical practice we typically use what insurance companies will cover,” Dr. Yee says. But he doesn’t see that as a bad thing, and he wouldn’t hesitate to recommend a biosimilar. “As far as I can tell, [the FDA has] done a good job of making sure the composition is similar enough that it does not have any impact on outcomes.”
The approval of trastuzumab-dkst was based on 2017 results from the HERITAGE clinical trial. Researchers randomly assigned nearly 460 people with HER2-positive breast cancer to receive either trastuzumab or trastuzumab-dkst along with taxane-based chemotherapy for 24 weeks. The findings showed that the original medicine and the biosimilar had similar effectiveness against the cancer and similar rates of common side effects. In June 2018, the researchers shared 24 more weeks of encouraging results.
If you are already receiving trastuzumab for HER2-positive breast cancer, it’s unlikely your doctor will switch you to trastuzumab-dkst or other Herceptin biosimilars when they become available. This is because the FDA has not said these medicines are “interchangeable” with trastuzumab, a rating it typically gives to generics, according to Jenna Carmichael, PharmD, a clinical pharmacist at Geisinger Cancer Institute in Wilkes-Barre, Pennsylvania.
“Our thinking is that if someone is [already] on treatment with a brand-name biologic such as Herceptin and they’re re-sponding, we’d keep them on it. But with new patients, there might be a discussion about whether they take the original medicine or the biosimilar,” says Dr. Carmichael.
How Biosimilars Could Change Treatment
Unlike most new medicines, biosimilars aren’t likely to change outcomes. But that’s OK: their goal isn’t to make treatment better, but to drive down the high cost of biologics. One year of Herceptin has a price tag of about $75,000. The cost is a huge burden for people who either don’t have insurance or have a plan that doesn’t cover the entire cost.
“Biosimilar manufacturers benefit from the work that another company has already done. That is how you get cost savings to the patient. But biosimilars are still pretty expensive to make, so we’ll see what the savings actually are,” says Dr. Carmichael.
“What biosimilars do have working in their favor is that a lot of them are already being used in Europe, safely and with good success,” she adds.
In Europe, where healthcare costs are mostly paid through governments, efforts to develop biosimilars started in 2006. Prices are running about 25 to 50 percent lower than the original biologics. In the U.S., biosimilar development didn’t get a push until 2009, after the Biologics Price Competition and Innovation Act passed as part of the Affordable Care Act. It created an approval pathway process for biosimilars. Eleven biosimilars have been approved in the U.S. for conditions such as cancer, arthritis and gastrointestinal diseases — with more expected as patents on biologics expire.
“I am a big believer in biosimilars,” says Dr. Stopeck. “Hopefully they will help decrease the cost of these enormously ex-pensive medications. And worldwide, this should allow more people in other countries the opportunity to receive these life-saving therapies.” She suspects that some patients with the resources to do so might insist on paying extra to receive the original medicine, but “I’d go with the more cost-effective drug if it has the same result.”
Genentech holds patents on two other HER2-targeting therapies that work with trastuzumab: ado-trastuzumab emtansine (Kadcyla), a combination medicine of Herceptin chemically linked to chemotherapy, and pertuzumab (Perjeta), a medicine used in combination with Herceptin and chemotherapy. These patents will keep biosimilars from being used in ado-trastuzumab emtansine and with pertuzumab for the time being. Also, there isn’t enough research yet to know whether a biosimilar could be substituted for trastuzumab in these therapies.
“These aren’t medications you walk into a drugstore and purchase. You would get them in a hospital or treatment center,” Dr. Yee adds — which makes it easier to ask what exactly you’re getting and why. If it’s a biosimilar, you can talk with your treatment team about what that means for you.