Lyman Reassures on Biosimilar Quality

Many things may discourage patients and doctors from using biosimilars, but they don’t dissuade Gary Lyman, MD, MPH, senior lead for Health Care Quality and Policy at the Hutchinson Institute for Cancer Outcomes Research.

In an interview, Lyman talked about some of the most common concerns and why they don’t trouble him about using biosimilars in cancer care.

“Drift” is one of the biggies. It can happen in the manufacturing of batch after batch of a biologic drug—biosimilar or originator product. It’s a subtle change in the makeup of the drug that occurs because these drugs are made from living organisms and are impossible to replicate with exact precision. Even batches of originator drugs are slightly different from earlier batches.

But biologics can be kept within predefined margins of quality. “While careful monitoring of the multiple attributes considered critical to a biologic is necessary, I am perfectly comfortable with using biosimilars in cancer treatment,” he said.

However, significant drift leading to a potential change in safety or efficacy could happen as easily to an originator product as a biosimilar, and in fact, this was observed in a recent phase 3 study, Lyman said.

Investigators sought to assess the cardiac safety and efficacy of trastuzumab originator and biosimilar products in patients with HER2-positive early stage breast cancer. They observed what they called a downward drift in immune system activity, or antibody-dependent cell-mediated cytotoxicity, for the originator version of trastuzumab, which led to superior event-free survival in the biosimilar arm of the study.

For this reason, “continuous monitoring of manufacturing and pharmacologic vigilance after approval are essential for both biosimilars and the originators,” Lyman said.

When it comes to conducting the pharmacokinetic (PK) and pharmacodynamic (PD) assessments needed to verify that biosimilar candidate drugs are equivalent to biologic originators, technology today “is far superior to what was utilized a couple of decades ago,” Lyman said.

The quality of these assessments are why it’s possible to project from PK/PD studies that biosimilars are highly similar to originator drugs and that clinical trials will yield equivalent outcomes and therefore may not be necessary.

Still, clinicians have shown hesitancy to put biosimilars to the test. These agents have been accepted more widely for use as supportive care agents than oncology drugs, Lyman said.

“Clearly, clinicians are more anxious about cancer treatment biosimilars than supportive care agents due to the potential impact on cancer outcomes and survival. This is understandable,” he said.

Lingering Obstacles to Uptake

There are other issues associated with the pace of uptake. Biologics are expensive, and biosimilars may not be offered at a very significant discount, Lyman said.

A decade ago, it was anticipated that biosimilars would enter the market at discounts to originators of 30% to 40%, but such hefty initial discounts did not materialize. Actual discounts to originators were in the range of 10% to 20%.

The billions of dollars of predicted savings may be years away, but earnings reports for biosimilar companies do show steady improvement in market share for this class of agents. International (non—United States) revenues for Humira (adalimumab) were $863 million, down 19.9%, in the second quarter of this year, owing to biosimilar competition.

Not Enough Competition

The danger is that having such limited competition in the biosimilar space may mean biosimilar manufacturers won’t be incentivized to offer deep discounts.

“In the United States, manufacturers of the initially marketed biosimilars may be more motivated to share in the very lucrative market of exorbitantly priced biologic therapies rather than compete directly by lowering prices significantly,” Lyman said.

“We do have some early evidence that the price associated with supportive care biosimilars has begun to decrease with multiple biosimilar competitors. Many of us hope that the prices of costly biologic agents for cancer treatment will also begin to decrease,” he added.

This may happen only slowly because of the way the US health care market is structured. “Lower prices are likely to improve access to these important agents and meaningfully reduce the financial burden or toxicity that patients with cancer experience on a daily basis.

“Although we remain hopeful that this will be the case, many believe that it will take more fundamental or structural change in health care financing in the United States for a real reduction in the enormous financial burden that patients with cancer and other serious illnesses face in the United States,” Lyman said.

A recent review published in the Journal of Clinical Oncology noted that biosimilars are causing a decrease in health care costs for biologics around the world while arguing that structural changes are needed to help the process along.