Herceptin (chemical name: trastuzumab) is a monoclonal antibody, a targeted therapy medicine used to treat HER2-positive breast cancers. Herceptin is what’s called a “biologic” drug. This means that it is made from living organisms, in this case a protein from a mouse cell. A monoclonal antibody is a type of protein made in the lab that can bind to substances in the body, including cancer cells. Each monoclonal antibody is made so that it binds only to one substance. Herceptin binds to the HER2 receptor proteins in cancer cells.
Because they are made from living organisms, biologic drugs are much more complex to make than conventional drugs that are made from a mixture of chemicals. The chemical structure of conventional drugs can be easily identified and duplicated, which is why there are so many generic drugs on the market.
A biosimilar is a new type of biologic drug. A biosimilar is almost identical to a biologic drug that is already approved by the U.S. Food and Drug Administration (FDA) (or similar organizations in other countries). It can help to think of a biosimilar as a generic version of a biologic drug, though that comparison isn’t completely accurate.
The makers of biosimilars don’t have access to the original cell lines used to make the biologic drug. They also don’t have access to the exact purification process or other manufacturing steps used by the makers of the biologic drug.
Biologic drugs can be very sensitive to changes in the manufacturing process. If one small step is done differently, the biosimilar may have very different effects than the original biologic drug.
So, the FDA requires the makers of biosimilars to show that a biosimilar drug is “highly similar” to the original biologic drug and is equally safe and effective before the agency will approve the biosimilar.
A study suggests that a drug that is a biosimilar to Herceptin, called MYL-1401O, is as effective and as safe as Herceptin.
The research was published online on Dec. 1, 2016 by the Journal of the American Medical Association. Read the abstract of “Effect of a Proposed Trastuzumab Biosimilar Compared With Trastuzumab on Overall Response Rate in Patients With ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Randomized Clinical Trial.”
The results, which were also presented at the American Society of Clinical Oncology Annual Meeting on June 3, 2016, are the first to show that a biosimilar to an approved biologic drug has the same effects on cancer as the original drug, according to Hope Rugo, M.D., professor of medicine at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center and lead author of the study. Dr. Rugo also is a member of the Breastcancer.org Professional Advisory Board.
In the study, 458 women diagnosed with metastatic, HER2-positive breast cancer were randomly assigned to receive one of two treatments:
- Herceptin with either Taxol (chemical name: paclitaxel) or Taxotere (chemical name: docetaxel) (228 women)
- MYL-1401O with either Taxol or Taxotere (230 women)
The women received a minimum of eight cycles of treatment.
None of the women had been treated with chemotherapy or Herceptin for metastatic disease, and 44% of the women had breast cancer that also was hormone-receptor-positive.
Metastatic breast cancer is cancer that has spread away from the breast area to another part of the body, such as the liver or bones.
Neither the doctors nor the women knew which medicine the women were getting.
After 24 weeks, the researchers looked to see how the cancers were responding to the treatment.
Overall response rates were:
- 69.6% for MYL-1401O
- 64% for Herceptin
After 48 weeks, there was no difference in either progression-free survival or overall survival between the biosimilar and Herceptin:
- progression-free survival rates were 44% for MYL-1401O and 45% for Herceptin
- overall survival rates were 89% for MYL-1401O and 85% for Herceptin
Progression-free survival is how long a person lives without the cancer growing. Overall survival is how long a person lives whether or not the cancer grows.
The risk of side effects also was similar for the two medicines:
- 57.5% of women getting MYL-1401O and 53.3% of women getting Herceptin had low white blood counts
- 23.1% of women getting MYL-1401O and 24.8% of women getting Herceptin had peripheral neuropathy
- 20.6% of women getting MYL-1401O and 20.7% of women getting Herceptin had diarrhea
The experimental biosimilar MYL-1401O has not been approved by the FDA yet, though Mylan, the company that makes MYL-1401O, filed a biologics license application with the FDA in November 2016.
Dr. Rugo said in an interview that if the new biosimilar is approved by the FDA, it could allow more access to treatment for women diagnosed with HER2-positive breast cancer.
“Lack of access is not a major issue in the United States,” she said, “because most patients have insurance that covers trastuzumab. I’ve not seen a situation where it wasn’t covered for a standard indication.”
Still, in other countries, cost can mean that some women don’t receive the treatment.
“It is expected that having biosimilars will reduce costs -- by some amount -- for these agents around the world,” Dr. Rugo said. Still, it is unclear how much less expensive biosimilars will be.
These results seem promising, but it’s not clear when or if MYL-1401O will be approved for use in the United States.
In an editorial that was published with the research, Howard Bauchner, M.D., editor in chief of the Journal of the American Medical Association, wrote that one of the sponsors of this study, Mylan, "has recently attracted attention because of the pricing, promotion, and involvement in the health policies of schools regarding one of its products, injectable epinephrine (EpiPen). There has been substantial criticism of the company by patients, physicians, and politicians about the recent price increase and the subsequent introduction of a generic epinephrine product by the same company.
"The proposed trastuzumab biosimilar will need to be priced at a level at which patients who otherwise would not have access to expensive therapies such as trastuzumab could receive needed therapy. In announcing their FDA submission for the proposed trastuzumab biosimilar, the sponsors of the trial by Rugo et al have expressed their 'shared commitment to increasing access to these critical medicines worldwide' and indicated that 'this advancement in the U.S. will enable us to enhance access to this affordable therapy to larger patient pools.' Ultimately, to fulfill these pledges the manufacturers must ensure that the pricing of this biosimilar product is responsible and fair and provides access to this important therapy at an affordable price."
While MYL-1401O is the first biosimilar cancer drug to be reported on, biosimilar drugs are being developed by a number of different companies. It’s likely that there will more studies in the future. So stay tuned to Breastcancer.org for the latest information on biosimilar drugs for breast cancer and what that might mean for you.
Editor's Note: On Dec. 1, 2017, the U.S. Food and Drug Administration approved Ogivri (chemical name: trastuzumab-dkst), a biosimilar for Herceptin, to treat people with HER2-positive breast cancer or HER2-positive metastatic stomach cancer. Ogivri was previously known as MYL-1401O. This article was updated on Sept. 27, 2019, to clarify information about biosimilars.