Biosimilars are coming to rheumatology. The Food and Drug Administration approved its first biosimilar earlier this year. And while rheumatologists are not likely to use Zarxio (filgrastim-sndz), similar to the original filgrastim, some of the most often-prescribed biologics in rheumatology could see biosimilar competition as early as next year.
“Infliximab, etanercept, adalimumab, and rituximab all have biosimilars in testing,” said Joseph E. Huffstutter, MD, of Arthritis Associates in Chattanooga, Tenn. “Legal wrangling may affect approval dates, but all of these products have the potential for coming off patent in the near future.”
Dr. Huffstutter will offer a preview of the ever-changing regulatory journey for biosimilars during a clinical symposium examining The Role of Biosimilars in Rheumatology Treatment from 4:30 – 6:00 pm today. Jonathan Kay, MD, Professor of Medicine, University of Massachusetts Medical School, will join Dr. Huffstutter as co-presenter.
Two dozen biosimilars have been approved worldwide, Dr. Huffstutter said, and at least 275 others are in development.
Unlike generics, which are chemical copies of approved drugs, biosimilars are not copies of approved biologics. Instead, biosimilars are similar to originator biologic agents with similar physical structures and similar therapeutic activity. Because they are similar to, and not identical to, originator agents, biosimilars must demonstrate both safety and efficacy in clinical trials prior to approval.
“We can use protein sequencing to ensure that the sequence of amino acids is identical, but there are tertiary and quaternary structures in a protein sequence that can be critical in terms of its effects and immunogenicity,” Dr. Huffstutter said. “When it comes to biosimilars, it is not just how well they work, but also how well they will be tolerated. Therein lie many of the issues.”
Methotrexate is methotrexate and carries a set of known clinical and adverse effects regardless of the manufacturer. That ability to manufacture a precise molecule and test for impurities is one of the advantages of small molecule agents.
Biologics are grown in biologic systems. Differences in cell cultures, growth media and growing conditions, the specific genetic manipulations used to insert the gene or genes needed to express the target protein, purification, and other manufacturing processes can all change the end product in clinically important ways. That potential for variation is an important reason regulators require clinical trials for biosimilars.
It’s relatively straightforward to demonstrate similar efficacy, Dr. Huffstutter said, and far more difficult to demonstrate similar safety profiles. He predicted that the FDA would require risk evaluation, mitigation, and safety (REMS) strategies for biologics as the agency now requires for many new drug approvals.
Adverse event monitoring raises other issues. Because biosimilars are different agents, prescribers need to know whether a patient is getting the innovator drug or a biosimilar and, if there are multiple biosimilars, which one.
“One of my concerns is that a patient may receive one biosimilar with one fill and another biosimilar for another fill,” he said. “If there is a problem, how does the prescriber know which agent is responsible? Some adverse events can take weeks to months to develop, time for the patient to have received multiple doses of multiple biosimilars.”
At the same time, powerful financial pressures drive approval and acceptance of biosimilars. Biosimilars typically cost around 60 percent of the originator biologic. That lower price expands the availability of biologic agents to patients who cannot afford innovator prices. Lower pricing could eventually factor into lower insurance premiums as a result of lower spending on biologic agents overall.
“The bottom line is that we all want what is best for our patients,” Dr. Huffstutter said. “Part of me is saying patients are doing well on current medicines and let’s not fix what isn’t broken. At the same time, I want to be a good steward. I don’t want to spend resources for an expensive product when a cheaper one may suffice. We know the journey to biosimilars has begun, we just don’t know what the destination will be like when we arrive.”