Biosimilars and Biologics
Reducing Patient Stress: A Dragon Claw White Paper
A Dragon Claw White Paper
Dragon Claw is a global website designed to support people with Rheumatoid arthritis (better called Rheumatoid disease), Lupus and children with Juvenile Idiopathic Arthritis (JIA). This White Paper has been circulated within the Dragon Claw community and incorporates member input. As such, it presents the opinions of a sample of patients from around the world. We are primarily concerned to ensure that the introduction of biosimilars does not increase patient stress, anxiety or pain.
The governments of Australia, Canada, France, United States of America and the United Kingdom (to name a few) are in the process of introducing biosimilar medications to replace the more expensive biologics used in the treatment of serious illnesses including Rheumatoid disease and Lupus. This paper outlines the issues and details a position in regard to the introduction of biosimilars from a patient perspective.
We speculate and our research suggests that many public health jurisdictions plan to encourage patients to switch from a biologic medication to a biosimilar one. Expected cost savings appear to be the main driver. Private health providers are likely to be less motivated unless patients request a change. From a pharmaceutical industry perspective a number of biologics are approaching the end of their patent period and this may allow generic manufacture to occur also potentially reducing costs while increasing patient choice. New and improved biologic therapy development by industry may also be a likely response to increasing competition. The above points imply that the cost versus effectiveness of these therapies is not predictably straightforward, thus making decisions around substitution on a jurisdictional basis more complex.
A biologic medicine is a large molecule typically made from living cells and used in the treatment, diagnosis or prevention of disease. Biologic medicines include therapeutic proteins, DNA vaccines, monoclonal antibodies and fusion proteins. Biologic medicines are often 200 to 1,000 times the size of widely used small molecule drugs and are far more complex structurally.
The safe and regulated introduction of biosimilars into the market has been forecasted to increase and improve access to much needed biologic medicines and reduce costs by as much as 30%.
Current International Situation
Today, there are over 200 biologics and vaccines on the market. Biologic medicines are currently prescribed to treat a wide variety of conditions, including Multiple Sclerosis, Rheumatoid disease, certain cancers and blood diseases.
In the past few years at least 31 states in the USA have considered or have enacted legislation establishing standards for the substitution of a “biosimilar” product to replace an original biologic product. In essence, the key issues relate to maintaining a list of acceptable ‘interchangeable’ products; that the prescribing clinician can insist on a patient not switching; and the individual patient be notified that a substitute or switch has been made. Our concern is that patient consent seems not to be a main consideration.
We believe that an independent authority charged with approving all new medications must be the sole agency to approve a biosimilar. This is the case already in some jurisdictions. We also believe that organisations and pharmacists who dispense biologics and biosimilars should not have the ability to substitute a biosimilar for a biologic. A determination of product interchangeability must not take the decision-making process out of the hands of patients and their specialists. We therefore support the position that only patients together with their physicians should decide the choice of product.
There are over 65 biological medicines currently funded through the Australian Pharmaceutical Benefits Scheme (PBS). Of the ten most expensive PBS medicines in 2013-14, five were biologics costing the taxpayer a total to government of $860 million. The Therapeutics Goods Administration (TGA) assesses all biosimilar medicines for efficacy in treating specific conditions but before a biosimilar medicine can be listed on the PBS, it must be deemed by the TGA to be as safe and effective as the reference biologic.
A standing rule in Australia is that the prescriber can prevent pharmacy level brand substitution by ticking the box on the prescription form which indicates no substitution is permitted. If the box is ticked, it is an offence under the PBS legislation for a pharmacist to dispense a brand other than that specified on the prescription. If the box is not ticked, it is assumed that good pharmacy practice requires the pharmacist to consult with the patient before substituting. These features, unlike a number of other jurisdictions overseas, seem to suggest that there is no automatic or uncontrolled substitution in clinical practice in Australia.
Unlike generic medicines where the active ingredients are identical, biosimilars are not likely to be identical to the original biologic. They are similar, but not the same. Biologics made by different manufacturers differ from the original product and from each other. This means that the process of switching, from the patient perspective, is likely to produce concerns as to how well the new therapy will address all their symptoms.
Research completed in the US in September 2015 indicated that ABP 501 as a biosimilar to adalimumab (Humira®) is highly similar. In addition, clinical equivalence between ABP 501 and adalimumab was demonstrated. The overall safety and efficacy of ABP 501 and adalimumab were similar. For the clinician there appears to be little difference but we would suggest that some symptoms considered important by the patient and less so by their doctor (fatigue or non-joint pain are examples) need to be taken in to account as well. From a patient perspective the wide variety of symptoms and the ability of the biosimilar to address the same symptom set as successfully as the original biologic is an area of potential stress and anxiety.
Rheumatoid disease and Lupus for moderate to severe sufferers brings on a great deal of stress, anxiety and depression. It is important not to unnecessarily exacerbate the situation by causing confusion or increased stress. Moving from a successful biologic to an unfamiliar biosimilar can be stressful for the individual involved. Education and detailed support from their clinician is essential. Involving the patient in the process and not relegating them to the status of ‘just a consumer’ will also assist to alleviate anxiety.
Issue 1: Switching back to the original if the biosimilar proves not beneficial
Conditions may arise where the original biologic medication fails the patient. At this point in time the specialist can opt for a replacement biologic or a biosimilar. In either case Dragon Claw is concerned about this as the opportunity is to issue a biosimilar that is very similar to the original biologic. Where failure has occurred the prescribing of a biosimilar is, in effect, a completely new therapy. In such a circumstance Dragon Claw recommends that the specialist and patient make a joint decision not influenced by external authorities and, if deemed necessary, return to the original biologic.
Issue 2: Appropriateness of pharmacy substitution without reference to the prescriber or to the patient.
Dragon Claw completely supports the position whereby the specialist can indicate on the prescription that no substitution is to take place. The fundamental position is education of the three parties involved. Dragon Claw recommends that governments and private providers take steps to fund, develop and issue educational material to patients, specialists, pharmacists and their staff.
Issue 3: There is no national system for monitoring the efficacy of the switch in terms of side effects and quality of life impact.
We understand that no jurisdiction has established such a monitoring system. A patient’s response to medications associated with Lupus and Rheumatoid disease broadly relates to the reduction in pain, stiffness, swelling, fatigue, disability, isolation and depression. A search of Internet resources has failed to locate data on patient responses by any national or jurisdictional body. Therefore we assume there is currently no systematic and reliable way of monitoring efficacy and improvements in the quality of life of patients switching from a biologic to a biosimilar. We also consider that biosimilar manufacturers should be required to produce and publish a risk management plan specifically related to the population characteristics of the likely user group. Dragon Claw recommends that a system of monitoring outcomes be established. In Australia, for example, this should be in parallel with national PBS authorisation for biosimilars.
Issue 4: Is it appropriate/reasonable to require a move to a biosimilar instead of another biologic when the primary biologic fails and a substitution is required?
In some ways this is related to Issue 1 previously. In addition, it would seem reasonable to move a ‘successful biologic patient’ to become a ‘successful biosimilar patient’ if there is a cost saving. This ideal condition supports both the patient and government intentions. We would argue that the rights of the patient must take preference in that if the biosimilar proves unsatisfactory the original biologic be re-instated i.e. a switch back. The monitoring of efficacy and the decision to switch back or to another medication is left to the prescribing specialist and the patient in consultation. While we have not found evidence to the contrary, it is important that no pressure be exerted to remain on the biosimilar line.
Issue 5: Should new patients be provided with a biosimilar as the first option?
Dragon Claw has no objection to this therapeutic approach for patients not currently using a biologic. Biosimilar therapy as a first step is appropriate provided the ability remains to utilise conventional biologics and other therapies should the initial biosimilar fail.
Issue 6: When the delivery mechanism is different from the original biologic to the new biosimilar (for example, self injection versus infusion).
There is an underlying assumption in much of the literature that the delivery mechanism used for a biologic therapy will be the same for a biosimilar. We can find very little discussion in the available literature of delivery mechanism changes. Changing delivery mechanisms can, we believe, be highly stressful for particular patients. Dragon Claw recommends that patients be fully informed and consulted.
Issue 7: The role of the pharmacist.
We object to the pharmacist having a decision-making role regarding the substitution of biologics for biosimilars. While this is not the case in Australia it is in some US jurisdictions (for example). Well meaning pharmacists do not have access to the patient’s medical record nor to their disease history. Consequently, Dragon Claw recommends that pharmacists are encouraged not to act independently.
July 2015, PBAC Meeting Record of consumer hearings
CONSUMER HEARING – BIOSIMILAR MEDICINES 7 JULY 2015: www.pbs.gov.au/consumer-hearing-record-on-biosimilars-2015
About Dragon Claw
Dragon Claw is a website and operation using online technologies to provide community and support for Rheumatoid Disease, Lupus and Juvenile Arthritis and care givers. We seek to empower the inflammatory disease community, advocate for positive change and shift the way medical professionals manage people with a chronic disease.
In Australia we have 3.3 million sufferers of general arthritis of which 450,000 are people with rheumatoid disease (including 5,000 children), which is the worst form of arthritis involving a life long painful chronic condition associated with very serious health consequences. This represents about 2% of the population with the ratio of males to females being around 1 to 3.
Dragon Claw is a registered not-for-profit company and is targeting a worldwide English speaking sufferer population of over 2 million with moderate to severe symptoms. Our patron is Dr. Mukesh Haikerwal AO. He is a former national president of the Australian Medical Association and is currently the chair of the Australian Institute of Health and Welfare.
 Cohen SB, Genovese MC, Choy EH, Perez-Ruiz F, Pablos JL, Zhang N, Kaur P. Randomized, Double-Blind, Phase 3 Study of Efficacy and Safety of ABP 501 Compared with Adalimumab in Subjects with Moderate to Severe Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/randomized-double-blind-phase-3-study-of-efficacy-and-safety-of-abp-501-compared-with-adalimumab-in-subjects-with-moderate-to-severe-rheumatoid-arthritis/.