Published in the Pharma Letter
18 October 2016
Earlier this month, initial results from a biosimilar switching study called “NOR-SWITCH” were released at the annual United European Gastroenterology Week meeting in Vienna. Data from switching studies such as these have the potential to impact how biologic medicines are used around the world. It’s important that policymakers do not misinterpret or exaggerate the findings, but instead use the data to develop medically appropriate policies. But what does data from NOR-SWITCH show? What is the study NOT designed to show? And how might the findings affect patients receiving biologic medicines?
Why does switching matter?
Biologic medicines are used to treat many serious illnesses such as cancer, multiple sclerosis, and arthritis. Biosimilars are similar but not identical copies of biologic medicines and, because they are generally available at a lower cost, have the potential to increase the number of patients who can receive life-changing medicines.
During the course of an illness, a physician may choose to transition a patient who has stopped responding to one biologic treatment to another different therapy. This is a medically supervised switch. The alternative is a non-medical switch, where patients who are stable on an existing biologic therapy are forced to switch to a biosimilar alternative, often as a result of healthcare policies meant to reduce costs.
Physicians, understandably, have some concerns about policies that force or encourage non-medical switching. They would also like to have data on the safety of switching.
NOR-SWITCH was designed to generate switching data for one specific biologic, infliximab, used to treat a variety of inflammatory diseases.
What is the NOR-SWITCH Study?
NOR-SWITCH is a randomized, double-blind study designed to evaluate the effects of a single switch from the original biologic (Remicade®) to the biosimilar (Remsima®, called Inflectra® in some regions) across six inflammatory diseases for which infliximab is approved. These include inflammatory bowel diseases like Crohn’s Disease, inflammatory joint diseases such as rheumatoid arthritis, as well as psoriasis.
Enrolling close to 500 patients, the study looked at disease worsening, disease-specific outcomes, safety, immunogenicity, and cost-effectiveness, to see if any of these measures were affected among those patient who switched to the biosimilar.
What is the study designed to show?
Data from NOR-SWITCH provides some important information on the effects of a single switch from the original biologic infliximab to a specific biosimilar infliximab.
It also helps us understand whether or not the switch stimulates any sort of immune response and whether that immune response has neutralized the effects of the infliximab. This was evaluated using serum samples collected from each patient at every visit throughout the course of the study.
What is the study NOT designed to show?
- The study is not designed to evaluate the effects of multiple switches throughout the course of treatment, a likely clinical scenario. For example, a patient starts treatment on biologic A, the medicine used by the hospital at the time to treat that patient’s illness. The hospital later changes the medicine they use to biosimilar A, so the patient is forced to switch. Then, the hospital switches to biosimilar B, and the patient is forced to switch again.
What effect, if any, does this have on the progression of a patient’s disease? This is an important clinical consideration for all those involved in patient care. And it has not yet been evaluated in any clinical study.
2. Similarly, the study does not examine the effects of switching from the original biologic to a different biosimilar within the product class, i.e. to a different infliximab that is not Remsima. This matters because the biologic and each biosimilar within a product class are similar but not identical to each other, and each may have subtle, but potentially medically significant differences.
3. Some might also point out that the study considers the effects of the switch by looking at how the disease worsens across all six diseases studied, rather than isolating the data for each disease state. Does this limit firm conclusions about the effects of the switch, since each illness is very different with regard to duration of response and clinical measures?
What will the results mean for patients?
Beyond offering new data, NOR-SWITCH also generates new questions. How will data from NOR-SWITCH impact health policy around the world? And what will this mean for patients? Will data from this study be used to justify policies that mandate switching of ANY infliximab biosimilar with the original infliximab biologic? Or multiple switches between lots of infliximab biosimilars over the course of a treatment period?
What about policies that apply the findings even more broadly, and generalize the data from NOR-SWITCH to justify wholesale switching between any biologic or biosimilar in a product class in any disease where biosimilars are used?
Studies like NOR-SWITCH are important in adding to the evidence base that can inform policies that govern the appropriate use of biosimilar medicines. It is important, however, that all stakeholders understand what the data do and do not show, and develop policies accordingly.
Governments around the world are under pressure to reduce healthcare spending. While it is tempting to use studies like NOR-SWITCH to provide air cover for polices deemed financially advantageous, good medicine requires that policy decisions reflect the data, and that decisions about switching remain in the hands of the treating physician and his or her patient.
Dr. Rieke Alten is head of the Department of Internal Medicine, Rheumatology, Clinical Immunology, Osteology at Schlosspark-Klinik, University Medicine Berlin, director of the Rheumatology Research Center, and member of the Global Alliance for Patient Access.
Sadie Whittaker, PhD, has over 10 years of experience in the biotech industry, working in the area of biosimilar policy since 2012. She received her PhD in molecular biology at University of Birmingham, UK, and her BSc in Biochemistry from University of Leeds, UK and is a member of the Global Alliance for Patient Access.