Natalizumab is one of 20-odd medicines prescribed for patients with the three major forms of multiple sclerosis (MS). Overall, North American revenues for all of the MS medications combined are about $15 billion, which is to say very substantial.
With other biosimilar introductions, the reference drugs targeted comprised the majority of prescribing either for that indication or for that overall category. For example, Herceptin® for the treatment of HER+ breast cancer, or Neupogen® and Neulasta® to prevent febrile neutropenia in patients receiving cancer chemotherapy. Or Remicade® for the treatment of active Crohn’s disease. Or Lucentis® and Eylea® for the treatment of age-related wet macular degeneration. Or Rituxan® as part of a chemotherapy regimen to treat non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Or Avastin®, to treat colorectal cancer (and a whole bunch of other valuable indications). Well, you get the idea. These are dominant products in their categories and as a result, they have high revenue potential for biosimilar manufacturers.
In the case of Tysabri, this is not true. The 2021 US revenue reported by its maker, Biogen, was $1.1 billion (annualized estimate based on third-quarter revenues). The reference drug is not only awash in competition from other drug makers, it is in competition with other MS drugs from its own manufacturer, Biogen, which also sells five others, including Tecfidera®, with 2019 sales of $4.4 billion. Biogen also has an EU approval for its subcutaneous Tysabri injection, which may also complicate future market competition in the US.
Roche’s Ocrevus® is the biggest seller, with 2020 revenues of $4.6 billion. Biogen also receives royalties on this product, to the tune of about $1 billion in 2021 (based on annualized figures). And this doesn’t account for new potential treatments for MS and complex generics that will be introduced in the coming years.
Tysabri utilization is expected to remain mostly steady in the coming years, but revenues are anticipated to decline slowly. A small fraction of its revenue is currently derived from its Crohn’s disease indication.
Sandoz and Polpharma Take up the Challenge
Sandoz, with its partner Polpharma, is the only biosimilar manufacturer who has publicly announced that its intent to commercialize a Tysabri biosimilar (PB006). The company, though certainly attracted to the glow of a $1 billion-plus product, also understands biosimilar marketing, with its actively marketed filgrastim and pegfilgrastim biosimilars (Zarxio® and Ziextenzo®, respectively) and a bit of frustration in biosimilar commercialization (e.g., its wait in the US to market Hyrimoz™ in the adalimumab space and Erelzi™ in the etanercept space). It is also worthwhile noting that PB006 would be the first biosimilar entry into the neurologic field, meaning that new emphasis will need to be placed on physician education and acceptance.
Finally, Tysabri has a bit of additional baggage—a black box warning for the risk of progressive multifocal leukoencephalopathy, a fatal brain infection, and the need for testing for the JC virus prior to administration, each of which Sandoz’s biosimilar candidate will likely have to bear. Sandoz has an advantage: It is not a newcomer to the MS space, having introduced its own complex generic glatiramer acetate product, Glatopa® in 2018.
According to Drug Patent Watch, the last of Biogen’s main patents on Tysabri expired in 2020. Based on the completion of its phase 3 clinical trial, a 351(k) filing may take place this year.
This natalizumab candidate may pave a new trail in the biosimilar industry’s journey, and it will be interesting to monitor Sandoz’s and Polpharma’s progress. Although they seem to have the biosimilar market open to themselves for MS, one expects that price differentiation will still be key. Another huge factor is Biogen’s portfolio interest in this space, with so many products. There are a lot of dynamics yet to be understood here.