The introduction of subsequent entry biologics (SEBs) is very different from the approval of a new generic medication.
By Mike Boivin BSc.Phm.
Their entry in the Canadian market will create some challenges and opportunities for every pharmacist in the country. Pharmacists need to be aware of the differences between SEBs and innovator biologics to be able to address questions and concerns from patients and prescribers alike.
Biologics are substances made from a living organism and produced through a highly complex manufacturing process. “We can’t think of these medications as just like any other medication filled in the pharmacy,” explains pharmacist Dan Martinusen from the Royal Jubilee Hospital in Victoria, British Columbia. “When most medications reach the end of their patent, the introduction of a generic is a relatively straightforward process. With SEBs, Health Canada does not view these drugs as ‘generic’ biologics and does not consider them interchangeable with the innovator product.”
An SEB’s approval in Canada does not go through the standard bioequivalence studies of generic products. The SEB manufacturer must perform safety and efficacy equivalence studies comparing the product to the innovator biologic. Since the trials are typically conducted in only a portion of the patient groups indicated for the innovator biologic, Health Canada may not approve the SEB for the same indications as the originator product.
“I think that many pharmacists don’t realize the potential challenges which SEBs create,” Martinusen notes. “Since these products are not interchangeable, we cannot just swap a patient on one product to the other. It is difficult to make the case to take a patient who is stabilized and doing well with the innovator product and switch them to another agent, where at this point we are not sure if it will have the identical efficacy and safety.”
SEB infliximab was recently approved for use in Canada. Like the innovator product, it is indicated for the management of rheumatoid arthritis, ankylosing spondylitis, plaque psoriasis and psoriatic arthritis, not for inflammatory bowel disease or Crohn’s disease like the innovator.
“This is one challenge for pharmacists: For some of these SEBs we will need to know the specific indication for the patient, which is different from typical generic medications which are substitutable for all the indications of the original medication,” says Martinusen.
SEBs are coming
He provides pharmacists with some suggestions to prepare for the potential introduction of multiple SEBs in the coming years:
1. “The substitution policy from brand to generic products does not apply. You can’t go from the innovator to the SEB or the reverse. Pharmacists will not only need to know what the patient was using but will need to ensure they are not switched inadvertently.” For pharmacy, this could mean the need to carry both the innovator and the SEB to satisfy the entire patient population.
2. The percent savings for SEBs are normally significantly less than with traditional generic products. “With the SEB manufacturer having to perform significant studies for approval of their product, the cost of entry is more expensive, and this is seen in the final cost of the medication.” Instead of being 75-82% less than the innovator product as seen with typical generic medication, SEBs are currently around 30% less costly than the originator. Given the expense of biologics, however, these savings are still valued by payers.
3. “Ideally, the choice of biologic should be made by patients and their physician. Pharmacists may feel pressure to recommend the SEB choice, and this likely makes sense only in the biologic naïve patient or in the patient experiencing a failure of another biologic.” It is important to assess the risk and benefits for the individual patient before considering the change.
4. “There are still some unknown issues with SEBs. Biologics are proteins which our body may recognize as foreign, and can mount an immune response to these products. This immunogenicity can decrease the effectiveness of the product, as one possible outcome. We are not sure if SEBs will lead to more or less immunogenicity than the innovator product.”
5. “I feel that all companies have tightly controlled manufacturing processes, but any changes in the process can potentially affect the safety and efficacy of these products. Health Canada requires all manufacturers to report any changes to ensure the product results in similar efficacy and safety over the long term. However, after approval, an SEB is not compared to the original biologic again. This may result in the two products drifting apart.”