The biologics sector continues to offer lucrative opportunities for future growth, but with relatively few contributions for the treatment of CNS indications. High-growth CNS market segments generally share one feature: biologics play a pivotal role in the treatment paradigm, or soon will. Neuromuscular-blocking biologics recently secured regulatory approval for chronic migraine. Alzheimer's disease is a high unmet need indication currently addressed only by symptomatic treatments, with potential for disease modification biologic therapies to play an important future role.
The example of biologics' success in the CNS market is highlighted largely by the success of therapies that target the multiple sclerosis (MS) disease process. This success has spurred some drug developers to increase their assets in this space and seek future opportunities for biologics in other CNS diseases. However, one important new reality that is slated to reshape the future landscape of this market is the introduction of biosimilars.
Unlike for generic pharmaceuticals, the development of a biologic and biosimilar molecule requires additional steps for ensuring access to target, bioavailability, bioequivalence and comparability of action, as well as clinical effect in the target patient population.
Biologics manufacturing: "The Process is King"
Being large and complex molecules, biologics cannot be fully defined by physicochemical analytical methods. They are manufactured from genetically modified living cells using complex processes, which inherently produce variability and product heterogeneity. In order to ensure product consistency, quality, and purity, the manufacturing process must be maintained substantially the same over time and across platforms.
For biosimilar development, the path presents additional challenges from the selection of the manufacturing platform, to analytical and immunogenicity assays, to in-vivo testing, and clinical trials. These clinical development programs generally do not undergo Phase II human testing, but rely on Phase III data in the absence of, sometimes crucial, phase II data that could have guided the program design on the best track forward. Additionally, for CNS biosimilars development, another hurdle presents itself: can the biosimilar cross the Blood Brain Barrier in the same fashion, and provide similar bioavailability and comparability, as the innovator molecule?
The jury remains out and has not yet declared the new face of the MS treatment landscape. Following nearly two decades of injectable therapies [interferon beta formulations, glatiramer acetate (Copaxone®)], the MS market has undergone notable change since the launch of new oral treatments in recent years: Novartis' Gilenya, Sanofi's Aubagio and most significantly Biogen Idec's Tecfidera.
Today, we must stop and ask yet an additional important question: Is the MS market ready, and willing, to endorse another storm slated to hit very soon?
Biosimilar pathways are already in place in the United States (US) and Europe. With the recent US court ruling in favor of allowing a biosimilar form of Copaxone® to reach the market potentially before the end of the year, a new paradigm shift is underway which is this time propelled by another driving force that, based on tried-and-tested precedents, risks to create a wider and deeper effect: biosimilars compelling price proposition. The Congressional Budget Office estimates that biosimilars initially are priced about 25 percent below their brand-name counterparts, and after several years of competition, would be priced as much as 40 percent below the brand.
If generic manufacturers succeed in launching a biosimilar version of the current MS market leading therapy Copaxone®, indicators point that the availability of a cheaper biosimilar will impact the market by creating price competition as well as potentially sway some payers to push back the use of more expensive injectable and oral therapies later in the treatment algorithm.
Considering the complexity of large molecule development, in the near future new insights will be learned about the paths taken and the distance crossed towards successfully launching a biosimilar in a major CNS indication that could inform future steps that others can take in the same direction.
Considering the complexity of the healthcare system delivery, new insights will be gained in order to better inform new developers about the fluctuating ratio of hesitation/adoption/adjustment of the market, in MS first and in CNS indications at large, considering the new reality in sight.
Finally, choosing a clinical development partner with proven expertise and understanding of biologics and biosimilars drug development paths and challenges, is critical to market success.
For advice on the clinical development of CNS biologics and biosimilars, or to speak with a Covance representative, please contact us.