Biosimilars: Too Expensive to Switch?

To switch or not to switch? When it comes to moving patients from biologic drugs to their less expensive biosimilar cousins, managed care plans and pharmacy benefits managers (PBMs) appear to be accelerating the process. CVS recently announced that it will move insulin glargine brands to its formulary exclusion list in 2017 in favor of the biosimilar Basaglar (insulin glargine injection; Eli Lilly). 

This leaves payers and PBMs to consider moving other originator products to exclusion lists as well, in the name of cost savings. Furthermore, Kaiser Health News’ monthly health tracking poll continues to show concern from consumers about rising prescription drug costs, with recent Affordable Care Act insurance premium increases for 2017 exacerbating their concern.

The line of demarcation on the issue appears to have been drawn between physicians, physician groups, and patient advocacy groups on one side, and payers, PBMs, and pharmacists on the other. Both contingents point to trial data to support their respective positions. Much of the data that favors switching comes from Europe, where biosimilars have been prescribed since the middle of the last decade. 

“The European Union has been at this for quite some time,” said Charles Karnack, PharmD, BCNSP, assistant professor of clinical pharmacy at Duquesne University. “They have not seen the problems we thought we were going to face in this country.” 

Switching Shows Promise In Europe

Catherine Cooke, PharmD, research associate professor at the University of Maryland School of Pharmacy, concurred with Dr Karnack. “In European countries where uptake of biosimilars has been good, data is emerging that appears to support short-term safety of switching among the products being studied.”

Examples include results from a Danish trial published in June, and data presented during the recent United European Gastroenterology Week meeting in Vienna.  

The Danish study by Bente Glintborg, MD, PhD, of the Gentofte University Hospital in Hellerup, Denmark, and colleagues, published in Annals of the Rheumatic Diseases involved 96 individuals with rheumatoid arthritis (RA), axial spondyloarthritis (SpA), or psoriatic arthritis (PsA) who had been taking the originator Remicade (infliximab; Janssen) for more than 5 years. Investigators looked at serum and antidrug antibody levels in patients who took the biosimilar for 2 or more months. The researches found that switching did not negatively impact either of the levels. 

Meanwhile, at the Vienna meeting in mid-October, results from NOR-SWITCH—the first randomized controlled trial to look at disease worsening in all indications in patients switched from originator to biosimilar infliximab—were presented. Nearly 500 participants with RA, SpA, PsA, ulcerative colitis, Crohn’s disease, or chronic plaque psoriasis who had been taking the originator for at least 6 months were included. They were randomized to continuation on the originator or switched to the biosimilar at the same dose. Disease worsening occurred in approximately 25% of those who stayed on the originator, vs approximately 30% in those who switched. The difference was in the pre-specified noninferiority margin. 

“Biosimilars… have the potential to save health care systems significant sums of money, and increase patient access to life-changing treatments,” said study co-author Jorgen Jahnsen, MD, PhD, professor of gastroenterology at the University of Oslo in Norway. 

Benefits of Switching Overstated?

Results like these are prompting managed care plans and PBMs to accelerate switching in an effort to hold down the cost of care.  When biosimilars—which are estimated to be anywhere between 10% and 40% less expensive than originators—are shown in trials to be noninferior, switching seems to make sense.  

Not so fast, say some experts, especially if there is no medical reason for switching. They contend that there needs to be an understanding that switching can sometimes lead to problems, which may make biosimilars less cost-effective than they appear at face value. Additionally, there are questions about the study power of some of the European data. Others wonder if results from countries with single-payer systems are directly relevant in the United States. 

Because NOR-SWITCH included patients with different kinds of autoimmune disorders, the patient groups for some of the conditions were small enough to raise questions for some. They wonder if simply seeing no negative implications—especially in the diseases where only 30 (PsA) and 35 (plaque psoriasis) patients were evaluated—can be meaningfully extrapolated for actual clinical practice. 

In addition, an industry expert with knowledge of the biosimilars market—who wished to remain anonymous due to a potential conflict of interest—pointed out that in the NOR-SWITCH study’s Crohn’s disease patient group, the loss of efficacy was 36% for the biosimilar, compared to 21% for the innovator.

Physician and patient advocacy groups have made additional critiques of the NOR-SWITCH study. A whitepaper released in September by the Global Alliance for Patient Access noted that the study demonstrated that switching can occur once; however, it did not show the effects of multiple switches from an originator to a biosimilar and then to another biosimilar. The group also pointed out the effects beyond the time period studied are unknown. 

Norm Smith, president of Viewpoint Consulting, Inc, which surveys managed markets decision-makers for the pharmaceutical industry, questioned the direct relevance in the United States of studies done in single-payer countries. He suggested that people might be more willing to switch in those countries. “You have a patient in Norway who receives free care and is happy about that, versus someone in this country who says, ‘Wait a minute, I’m 75 years old, I don’t know how this injector works, and I really don’t want to change.’” 

Faced with such circumstances, physicians in this country are apprehensive about switching, he said. 

Costs of Switching Studied

Experts noted that there is also data that suggests that switching for any reason—including a non-medical one—can end up being costlier than not switching. A retrospective claims analysis involving more than 2800 individuals with psoriasis compared a group of patients who switched targeted immunomodulators within the first year of initiating treatment with a contingent of nonswitchers. Medication costs for switchers averaged ~$30,000, 15% higher than they were for nonswitchers. Outpatient costs were nearly $2700 for switchers, about double the cost for nonswitchers; and physician costs were $345 for switchers, about 50% higher than those incurred by nonswitchers. 

Another retrospective pharmacy claims analysis involving more than 6600 individuals with RA compared people who switched from an immunomodulator to a different disease-modifying antirheumatic drug within 90 days with those who refilled their immunomodulator prescription with the same medication within 90 days.  As a group, switchers incurred an average of 0.32 emergency department (ED) visits per patient, vs an average of 0.20 visits per patient for nonswitchers. They also averaged  approximately 22 outpatient visits, vs approximately 17 for non-switchers. Switchers also had more RA-related outpatient visits and rheumatologist visits. 

Some have noted that added copays and payer costs for office visits, drug titrating costs, ED visits, hospitalizations, and lost worker productivity for employers should all be considered when factoring the value of nonmedical switching. Others acknowledged the issue, but advocate taking a closer look first. 

Barney Spivack, MD, national medical director of Medicare case and condition management at OptumHealth, said that patient questions about switches involving equivalent medications “may be able to be answered by the prescriber or pharmacist telephonically.” Still, he added that, “switching to a biosimilar brings… potential concern for loss of a maintained therapeutic effect. It is understandable that questions from patients will need to be carefully addressed to ensure adherence.” 

Mr Smith pointed out that some costs are difficult to attribute to a single reason. “Can you pin hospitalizations on simply switching from one drug to another? It may not be because of the drug itself, but because [a physician doesn’t] know how to make the switch,” which could be avoided with adequate education and training. 

Others said that some analyses might be overreaching. “Lost productivity time would never be brought up by employers,” explained Gary Owens, MD, president of Gary Owens Associates. “Less than 1% of members use biologics, so any lost productivity to that small segment would be immaterial.”

Reluctant to Change What Already Works

Mr Smith said he believes physicians as a group are reluctant to make changes. “The first rule of medicine is if it ain’t broke, don’t fix it,” he noted, paraphrasing the Hippocratic oath. Mr Smith cited two recent examples he’s seen in his own research. One involves the anticoagulants Xarelto (rivaroxaban; Janssen) and Eliquis (apixaban; Bristol-Myers Squibb/Pfizer). 

“Xarelto was first marketed as a safer and just-as-effective alternative to warfarin, but that turned out to be wrong,” Mr Smith said. “These anticoagulants are not only safer but more effective than warfarin. Yet when you look at market share of anticoagulants, 50% of people are still taking warfarin.” 

Mr Smith also pointed to the heart failure drug Entresto (sacubitril/valsartan; Novartis), which has been shown to reduce hospitalizations and ED visits compared to using a diuretic/ACE inhibitor/ ß-blocker combination. Yet physicians are reluctant to switch. “When we asked cardiologists why this was so, they said they did not want to interfere with something that is already working.” 

Physician groups, such as the American Academy of Dermatology, the American College of Rheumatology (ACR), and others are backing up their members on the issue of biosimilar switching. ACR notes in a position statement that there should be “safeguards that prevent payers from forcing patients who are responding adequately to their current biologic therapy from switching to a biosimilar.”

Absolute Exclusion Not Likely

Mr Smith said it is important to keep in mind that placing medications on formulary exclusion lists is an overall policy decision, but it does not necessarily mean absolute exclusion for every patient. 

“Some companies, like Blue Shield of California, are hesitant to make radical changes in a patient’s therapy,” he said. “I think you will see more grandfathering as the exclusions come out. These will be ‘one-off’ decisions based on the individual care setting.”

Dr Spivack said he agrees that grandfathering provisions will help manage transition to biosimilars. “More often it’s new starts that are [given] a new product.” 

Dr Owens noted that he sees grandfathering as a safe approach, “but it will go by the wayside if biosimilars prove to be equivalent products.” Until then, he said he thinks that payers will incentivize patients with lower out-of-pocket costs to voluntarily switch.

Mr Smith added that he believes that over time the originator drugs will be priced competitively with biosimilars—but only to a point. 

“When discounting gets above 25%, I think companies with originator products will not follow the biosimilar companies into a pricing spiral,” he said. 

Dr Karnack, a pharmacist, took the issue from the theoretical to the practical. “For the majority of patients, I don’t think [switching] is going to be a problem.” Yet, he said he understands that certain patients are not candidates for switching. “So if I am filling a prescription for a patient with Crohn’s disease and the physician wants to use an [originator product], I am going to ask for clinical documentation proving why a [nonmedical] switch is [ill-advised]. Too often I see opinions that are not backed up by clinical evidence.” 

Dr Cooke agreed, but noted that even the European countries where biosimilars have been used for years lack long-term evidence. “We need data on how well these products can be interchanged within individual patients. The unique challenges that products such as monoclonal antibodies present increase concern over safety events such as immunogenicity. Additional data will provide guidance [so that] patients, clinicians, and payers can determine the comparative value of biosimilars.”