A new biosimilar version of the monoclonal antibody trastuzu­mab (Herceptin) is getting close to the finish line in the race to develop biosimilars in oncology. The new antibody, MYL-1401O, demonstrated comparable efficacy and safety compared with trastuzumab as front-line treatment of women with HER2-positive advanced breast cancer, according to 24-week results of the randomized phase III ­HERITAGE study presented at the 2016 ASCO Annual Meeting.¹

Hope S. Rugo, MD

The 24-week objective response rate was 69.6% for MYL-1401O vs 64% for branded trastuzumab. Safety was comparable between the two groups.

“To our knowledge, this is one of the first clinical trials to show equivalency of a biosimilar to the branded cancer drug,” said lead author Hope S. Rugo, MD, Professor of Medicine at the University of California San Francisco Comprehensive Cancer Center.

Expanded Access, Lower Cost?

“Trastuzumab markedly improves survival in women with HER2-positive breast cancer, but many women around the world can’t get this drug due its high cost,” she continued. “The hope is that the introduction of a biosimilar will expand patient access to this effective drug,” she added.

Although it is hoped that the cost of the biosimilar will be substantially lower than that of the branded product, Dr. Rugo said she did not know what the cost of MYL-1401O will be when—and if—it is approved by the U.S. Food and Drug Administration (FDA).

“As researchers, we don’t know how pricing is determined and we don’t have the answer to what the new trastuzumab biosimilar will cost. It is expected that biosimilars will reduce the cost by some amount. This is less of an issue in the United States, where most patients have insurance that covers branded trastuzumab for the standard indication,” she told listeners at a press conference during the ASCO meeting.

Only one oncology biosimilar is FDA-approved thus far: filgrastim-sndz (Zarxio), which is marketed for about 15% less than the reference product (filgrastim [Neupogen]) in the United States. In Europe, the pegfilgrastim (Neulasta) biosimilar costs about 25% less than the reference product.

Study Details

HERITAGE was a randomized, double-blind, phase III trial conducted at 95 sites across Asia, Latin America, and Europe. The study randomly assigned 458 women with metastatic, HER2-positive breast cancer to first-line treatment with a taxane (docetaxel or paclitaxel, left to the institution’s choice) plus MYL-1401O vs a taxane plus trastuzumab for at least eight cycles. Patients with stable disease after eight cycles continued treatment with their assigned drug (MYL-1401O or trastuzumab) until disease progression.

Trastuzumab markedly improves survival in women with HER2-positive breast cancer, but many women around the world can’t get this drug due its high cost. The hope is that the introduction of a biosimilar will expand patient access to this effective drug.

— Hope S. Rugo, MD

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For regulatory approval, the FDA required the primary endpoint to be objective response rate ratio, whereas the European Medicines Agency (EMA) required it to be the difference in objective response rate. At 24 weeks, objective response rate was 69.6% for the biosimilar vs 64% for branded trastuzumab. The difference in objective response rate was 5.5%, which fell within the equivalency range.

Immunogenicity and safety were comparable between treatment arms. The rate of serious adverse events was 38.1% in the biosimilar arm vs 36.2% in the trastuzumab arm. Neutropenia was the most common serious adverse event in both arms (27.5% vs 25.2%, respectively), and no difference in cardiac function measures was observed between the two arms. Both arms had a similar rate of antidrug antibody formation: 2.4% and 2.8%, respectively. There were few cases of pneumonia “attributable to the taxane,” Dr. Rugo said, and the rate was similar in both arms.

“The antibody rate is consistent with published trastuzumab data showing a low immunogenic potential,” she said.

Additional Comments

These results using a proposed biosimilar are incredibly exciting. This has the potential to broaden access to a lifesaving agent. I await further results.

— Don S. Dizon, MD, FACP

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“These results using a proposed biosimilar are incredibly exciting. This has the potential to broaden access to a lifesaving agent. I await further results,” said Don S. Dizon, MD, FACP, Chair of ­ASCO’S Cancer Communications Committee and moderator of the press conference where Dr. Rugo presented these results.

The trastuzumab biosimilar is not yet FDA-approved, but it appears that 24-week results meet the regulatory requirements for a biosimilar: They demonstrate structural and functional similarity to the reference product; similar pharmacokinetics and pharmacodynamics; and confirm similar safety, efficacy, and immunogenicity. ■

Disclosure: Dr. Rugo has received honoraria from Genomic Health; research funding (institutional) from Celsion, Eisai, Genentech, GlaxoSmithKline, Lilly, Macrogenics, Merck, Nektar, Novartis, OBI Pharma, Pfizer, and Plexxikon; and reimbursement for travel, accommodations, and expenses from Mylan, Nektar, Novartis, OBI Pharma, and Roche/Genentech; and is a member of the speakers bureau for Genomic Health. Dr. Dizon reported no potential conflicts of interest.

Reference

1. Rugo HS, Barve A, Waller CF, et al: Heritage: A phase III safety and efficacy trial of the proposed trastuzumab biosimilar MUL-1410O versus Herceptin. 2016 ASCO Annual Meeting. Abstract LBA503. Presented June 6, 2016.