Sandoz’s Erelzi receives FDA Approval making it the First US Enbrel Biosimilar

21st November 2016 (Last Updated July 18th, 2018 13:27)

Sandoz announces the FDA’s backing of the biosimilar, Erelzi

Sandoz’s Erelzi receives FDA Approval making it the First US Enbrel Biosimilar

Sandoz, a Novartis company, has announced its drug, Erelzi, has been approved by the FDA, in a significant development. The drug, designed to treat adults with psoriatic arthritis (PsA), ankylosing spondylitis (AS), plaque psoriasis (PsO), rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS), represents the US’ first Enbrel biosimilar.

While in 2015, Amgen’s Enbrel had US sales of roughly $5.1 billion, the approval of Erelzi means it will face stiff competition going forward as the new drug will offer the first subcutaneous anti-tumor necrosis factor (anti-TNF) biosimilar to US patients. Although the launch date for Erelzi is unknown, experts at GlobalData predict the biosimilar will have a significant impact once it’s released.

Enbrel, marketed by Amgen in the US and by Pfizer in most countries outside the US, is a leading biologic agent that is approved for multiple immunological indications, including RA, PsO, and AS. It is a fusion protein made by recombinant DNA technology, where the TNF receptor is combined with the Fc portion of human immunoglobulin G1 (IgG1). Enbrel binds to and neutralizes both lymphotoxin and TNFα, thus preventing synovial inflammation. Enbrel was originally due to come off patent in the US in October 2012 when the design of biosimilars was already underway in Europe and Asia. However, in November 2011, Amgen announced that it had received an extended patent for Enbrel in the US, protecting it from Erelzi and other Enbrel biosimilars until 2028. Amgen will benefit dramatically from this patent extension, as Enbrel’s $5.1 billion in US sales accounts for more than half of the drug’s annual global sales.

Erelzi, which will be manufactured and commercialized by Sandoz, was approved following a unanimous vote by the FDA’s Arthritis Advisory Committee on July 13, 2016 for all indications of the reference product. The recommendation was based on the successful completion of a global development program including analytical, pre-clinical, and clinical data of Erelzi, which exhibited biosimilarity to Enbrel. Clinical studies consisted of four comparative pharmacokinetic studies in 216 healthy subjects as well as a safety and efficacy similarity study in 531 chronic PsO patients. These findings mark a substantial turning point to the immunology market, as Erelzi, priced at a discount to Enbrel, will allow for the expansion of anti-TNF treatment for patients with chronic inflammatory conditions. GlobalData anticipates that Erelzi, which is also undergoing review by the European Medicines Agency (EMA), will bring in significant revenue for Sandoz, as Enbrel accounts for approximately $3.6 billion in annual sales outside of the US.

Bearing in mind the high annual cost of biologics therapy, particularly for chronic immunological diseases, Erelzi will not generate the same kind of cost savings for healthcare payers and patients that are generated by small-molecule generics. The manufacturing of Erelzi, which must be similar in terms of quality, safety, and efficacy to Enbrel, is expensive. Key opinion leaders (KOLs) interviewed by GlobalData expressed concern regarding the pricing of biosimilars, which are expensive compared with synthetic generic drugs. In the US, Sandoz’s Zarxio, a biosimilar version of the branded granulocyte colony-stimulating factor biologic Neupogen (filgrastim), is priced at an 15% discount to its branded reference product. As such, GlobalData anticipates that Erelzi will be priced at a discount close to this in relation to Enbrel. Further, Erelzi was approved as a biosimilar and not as an interchangeable biologic product, meaning Sandoz’s Enbrel biosimilar cannot be interchanged with the reference product by the pharmacist without the intervention of the prescribing healthcare provider. The FDA is set to release biosimilar interchangeability standards later this year.

Like all biosimilars, Erelzi will receive greater scrutiny than is given to generics in the clinical setting. Although KOLs interviewed by GlobalData believe that biosimilars are safe and effective alternatives to the branded biologics, high-prescribing rheumatologists surveyed by GlobalData revealed that they expect anywhere from 0–40% of their RA patients to take the biosimilar over the branded drug. KOLs interviewed by GlobalData identified a major concern regarding biosimilar uptake to be the reputability of the manufacturers. GlobalData’s primary research also revealed that rheumatologists are unlikely to prescribe biosimilars for RA patients who are already stable on the branded product, and would request that switch studies be conducted. The acceptance of biosimilar products is likely to change over time as more information on their use becomes available from larger-scale clinical trials and from experience using them in clinical practice. Further, rheumatologists interviewed by GlobalData said they felt reasonably comfortable with the use of biosimilars, provided that Phase III bioequivalence studies are conducted in the indication for which they are approved. Thus, GlobalData expects that the adoption of Erelzi will be faster in PsO than in PsA, RA, AS, and JIA.

Sandoz is not alone in the race to bring biosimilars to the US market. Although Sandoz will not face competition from other Enbrel biosimilars in the US in the near future, the company will experience pressure to attain first-to-market advantage for approval of biosimilars of AbbVie’s Humira (adalimumab), a TNF inhibitor, and Biogen’s Rituxan (rituximab), a CD-20 inhibitor. In January 2016, Amgen announced the FDA accepted their Biologics License Application (BLA) for review for ABP 501, a Humira biosimilar, with a Biosimilar User Fee Act target action date of September 25, 2016. Sandoz’s Humira biosimilar is in Phase III development and unlikely to attain first-to-market advantage with Humira’s patent expiring this year. Further, Rituxan’s patent expires in 2018 leaving Sandoz’s Phase III biosimilar with stiff competition from numerous companies including Pfizer and Celltrion, all with Rituxan biosimilars in Phase III development. Although Sandoz has attained first-to-market advantage for two of the three biosimilars approved in the US, its current command of the biosimilar market will be short-lived if Amgen’s, Pfizer’s, and Celltrion’s biosimilars reach the market before Sandoz’s pipeline biosimilar products.

*This article first appeared on GlobalData.com on 2nd September, 2016