Biosimilars are the new hot topic in the biopharma world, and as more of them become available globally, physicians, payers and patients alike are keen to understand the safety of switching between these copycat drugs and their original biologic medicines.
The highly-anticipated NOR-SWITCH study was released last month at the annual United European Gastroenterology Week meeting in Vienna, and was billed by many industry players and a number of physicians as the definitive answer to the question of switching between biologics and biosimilars - claiming it should put paid to any concerns among physicians or patients.
Undoubtedly this widely-reported trial - commissioned by the Norwegian Government - now has the potential to influence policies that govern biological medicines and impact how biologic medicines are used around the world. Governments, regions and hospitals globally are under pressure to reduce healthcare spending and maximise treatment for patients on tighter-than-ever budgets.
But the Global Alliance for Patient Access (GAfPA) - a network of physicians and patient advocates that campaigns for patient access to appropriate clinical care and approved therapies - believes it is important that policymakers do not misinterpret or exaggerate the findings of the NOR-SWITCH trial. In fact, it is GAfPA's strong belief that the study's results should not be used by policymakers as a basis to permit wholesale switching of all patients in every instance. More importantly, as a patient-led organisation, we believe it is imperative that any switching that takes place should involve physician participation and informed patient consent - arguably the key tenets in any treatment decision.
So what is the background to the NOR-SWITCH study? What does the data from NOR-SWITCH actually show? More crucially, what is the study NOT designed to show - and finally, how might the findings affect patients receiving biologic medicines?
GAfPA has closely considered the strengths and limitations of the NOR-SWITCH study in our white paper, NOR-SWITCH: What will Norway's infliximab switching study tell us about the safety of switching patients from one biologic medicine to a biosimilar? The paper, published in September and available in English, French, German and Spanish, stems from discussion among an international group of physicians and researchers who met in London in June with NOR-SWITCH investigators to discuss the switching study and its potential impact. The group included leading clinicians from the fields of rheumatology, gastroenterology and dermatology.
What is the NOR-SWITCH Study?
NOR-SWITCH is a randomised, 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 and 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 patients who switched to the biosimilar. Patients were enrolled from 40 sites across Norway and monitored for 52 weeks. The patient populations for each indication were: 155 Crohn's disease, 93 ulcerative colitis, 78 rheumatoid arthritis, 91 spondyloarthritis, 30 psoriatic arthritis and 35 plaque psoriasis.
NOR-SWITCH is designed to evaluate the effects of a switch from the original biologic to a 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 neutralised the effects of the infliximab. This was evaluated using serum samples collected from each patient at every visit throughout the course of the study. Some have argued that the data would be more meaningful if it had been powered to show disease-worsening within each disease area.
What is the study NOT designed to show?
1. 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 it uses 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, ie 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? Biosimilars are inherently different from their reference product and in addition they are approved according to different standards. Accordingly, there needs to be extra caution exercised when extrapolating between conditions.
4. The study does not show the effects of switching in different diseases treated with other biologics and biosimilars not studied in NOR-SWITCH.
5. Finally, while switching a stable patient from a biologic medicine to a biosimilar for non-medical reasons may bring cost savings in the short term, we know from our own research that this may disrupt a patient's course of care and result in higher costs in the long term.
What does all this mean for patients?
Over the past year GAfPA has held a number of workshops across Europe with patient advocacy groups on the subject of biologics and biosimilars - notably in Barcelona in February 2016 with over 60 patients with immunological conditions, as well as a meeting of Nordic patient advocates in Copenhagen in October. At every turn, patients have overwhelmingly raised their concerns with us about the impact of patients, who have fought hard to become stable on a treatment, switching to a biosimilar. Other key concerns raised at our meetings have been the lack of information given by physicians intent on switching patients, the lack of adequate tracking and tracing of biologic and biosimilar medicines in the case of adverse events, and critically, how physicians go about ensuring there is meaningful and informed patient consent when deciding to switch a patient.
GAfPA firmly believes that 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 does and does not show, and develop policies accordingly. 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. More importantly, we will continue to support our view that decisions about switching should always remain in the hands of treating physicians and their patients.