BY PAUL KLEUTGHEN
Over the years we have become familiar with generic drugs, approved by FDA, and treated as the same as their brand-name cousins by physicians, pharmacists and medical insurers. These substitutable (for the original version) medications come as both oral and injectable/infusible drugs.
The exception, however, was for those products that were approved by FDA under a Biologics License Application (BLA), which is different than drugs approved under a New Drug Application (NDA). Biologics are made from living cells, tissue or blood as opposed to products manufactured through chemical processes. The generics for the biologics are called biosimilars.
There has been a clear regulatory path to approve generics for those NDAd drugs since the mid 80s but the regulatory road for biosimlar drugs was not established until a few years ago. Examples that myeloma patients are familiar with are Thalomid, Revlimid, Pomalyst or Velcade, approved as NDA products and just about any compound ending in mab (for Monoclonal Antibody, such as Darzalex or daratumumab) as a biosimilar drug.
In the upcoming weeks, some of us may see the use in the treatment centers of the first biosimilar approved in the US by FDA : filgrastim (Neupogen brand). Filgrastim is typically used to increase the white blood cell count in patients before a stem cell transplant. (Ah, the good ol days when we first learned to inject ourselves ! Or when our caregivers tried it and said On the count of three One, two, three and then nothing happened on that count of three. How time flies when you are having fun !)
And now the question arises : is this biosimilar filgrastim the same as the Neupogen brand ?
And the answer is well, not exactly. But the FDA has mandated a very rigorous set of requirements to be met that make it quite the same. The key is that the biosimilar must demonstrate that it is:
expected to produce the same clinical result as the reference product [in this case Neupogen] in any given patient.
In addition, the biosimilar also has to prove that there is no loss in efficacy or safety when switching between the biosimilar and its reference product (and do so both ways : from brand to biosimilar and then back to brand) to mimic reality of what may happen in the clinic. It needs to be understood, however, that the biosimilar only has to prove comparable efficacy to the originator products for one of the approved indications through human clinical trials whereas the originator secures FDA approval for other indications through submission of additional clinical studies. The biosimilar, however, needs to provide robust scientific justification of the products mechanism of action, immunogenicity and safety risks, and several other requirements. The biosimilar will be granted approval for the products other indications only if these data are acceptable to FDA.
In some cases, FDA may also require post-market studies to monitor safety and/or efficacy issues (pharmacovigilance studies) seen with the use of the biosimilar. Physicians play a significant role here and need to understand that it is important to submit adverse event reports to FDA (passive studies) or whether they will participate in studies that utilize claims to evaluate outcomes (active studies).
What does it all mean for the patient ? The cost of the biosimilar will be lower than for the originator. By how much ? That remains to be seen but a conservative estimate will be 20 percent. That is a material number. The cost of cancer biologics in the US has doubled in the period 2006-2012, and continues to do so at similar annualized rates. The annual cost of treatment with some biologics now exceeds $ 200,000. Patients need to be aware that if the prescription is written for the Brand name, their out-of-pocket cost may be significantly higher based on the design and definition of their medical insurance program (and that includes Medicare Part B). So, for those coming close to using filgramstim/Neupogen, prior to transplant, it will be well worth to call the insurer as well as discuss which product your physician intends to prescribe and use. Medicare rules provide a financial incentive for institutions to utilize the biosimilar to lower the total cost to the Federal Government.
Biosimilar filgrastim will be the first of many more to come. Over the next few years we will see a steady increase of the number of biosimilars that will come to market, most of them will provide less costly treatments for a variety of cancers, though not quite yet in the multiple myeloma segment. It is estimated that between now and 2024 the introduction of biosimilars will reduce spending on biologics in the US by + $ 40 billion.
For those interested in seeing what wealth of data the marketer of this first approved biosimilar (Sandoz) used in its discussion with a FDA Advisory Committee in January 2015 you may wish to browse through the + 150 page document. This document also informs the reader that the Sandoz filgrastim has been available in Europe since 2009 and over the period 2009-2015 was used in 7.5 million patient treatment days.
about the author
I am a patient diagnosed in 2014 with primary plasma cell leukemia (pPCL), a rare and aggressive variant of multiple myeloma and have been very fortunate to find successful treatment at the division of Cellular Therapy at the Duke University Cancer Institute. My wife, Vicki, and I have two adult children and two grandsons who are the ‘lights of our lives’. Successful treatment has allowed Vicki and I to do what we love best : traveling the world, albeit it with some extra precautions to keep infections away. My career in the pharmaceutical industry has given me insights that I am currently putting to use as an advocate to lower drug pricing, especially prices for anti-cancer drugs. I am a firm believer that staying mentally active, physically fit, compliant to our treatment regimen and taking an active interest in our disease are keys to successful treatment outcomes.