Samba Epis 'Hadleema' Interchangeability Approval Process Initiated

Original 'Pharmacy Substitution Dispensing' Possible
Approval Expected to Contribute to Market Share Increase

Samsung Bioepis's autoimmune disease treatment 'Humira' (active ingredient adalimumab) biosimilar 'Hadlima' is entering the formal approval process by the U.S. Food and Drug Administration (FDA) to secure interchangeability, a key weapon to capture the U.S. Humira market worth approximately 25 trillion KRW.

Samsung Bioepis's Humira biosimilar 'Hadlima'
[Photo by Samsung Bioepis]

Samsung Bioepis and its U.S. partner Organon announced on the 8th that the preliminary review of the biosimilar biologics license application (sBLA) for Hadlima's interchangeability certification, submitted to the FDA last August, has been completed and the formal review process has begun.

This supplemental approval application was based on a follow-up Phase 4 clinical trial conducted to confirm the pharmacokinetic similarity between the original drug and the high-concentration formulation (HCF) of Hadlima in patients with moderate to severe plaque psoriasis. The clinical trial was conducted from August last year to May this year in Eastern European countries including Poland, the Czech Republic, and Lithuania, involving 371 patients with moderate to severe plaque psoriasis. Until week 12, patients were administered the original drug, and from week 13, a 1:1 randomized allocation was applied where the maintenance group continued the original drug, and the crossover group alternated between Hadlima and the original drug. As a result, the primary endpoints set by the area under the concentration-time curve (AUC tau) and maximum serum concentration (Cmax) at weeks 23 to 25 met the predefined equivalence criteria. Efficacy, safety, and immunogenicity were also similar.

AbbVie's autoimmune disease treatment 'Humira (active ingredient Adalimumab)'

Proving interchangeability is important due to the nature of biologics. Because biologics are derived from living organisms, it is impossible to create an exact copy of the original drug; only similar copies can be made. This is why biosimilars have distinct nonproprietary names such as 'adalimumab-bwwd (Hadlima)' and 'adalimumab-aaty (Yuflyma)'.

Therefore, unlike generic synthetic drugs, biosimilars are generally not allowed to be substituted at pharmacies in the U.S. However, if interchangeability is proven, pharmacists can autonomously substitute an interchangeable biosimilar even if the physician prescribes the original drug, enabling increased market share. This is especially significant in the adalimumab market, where patients receive prescriptions at pharmacies and self-administer injections or pens at home, making interchangeability even more meaningful.

Boehringer Ingelheim's Humira biosimilar 'Siltezo'
Photo by Boehringer Ingelheim

In fact, among Humira biosimilars, Boehringer Ingelheim's 'Cyltezo', which has been recognized by the FDA for interchangeability, is a low-concentration product with lower preference compared to the adalimumab HCF product, yet it is consistently listed on formularies of major Pharmacy Benefit Managers (PBMs). Samsung Bioepis expects that Hadlima, developed in both low- and high-concentration formulations, can have all concentrations recognized for interchangeability, allowing for a more effective market strategy.

Celltrion is also conducting clinical trials aiming to secure interchangeability for 'Yuflyma' by the end of next year, and Amgen (Amjevita) is also developing interchangeability. However, the FDA has recognized only seven biosimilars as interchangeable, including Humira biosimilars Cyltezo and Abrilada (Pfizer), Lantus biosimilars 'Semglee' and 'Rezvoglar', Lucentis biosimilars 'Simbrinza' and 'Byooviz', and Stelara biosimilar 'Wezlana'.

Even if Hadlima is recognized for interchangeability, actual substitution through this will likely only be possible after July next year. This is because the first biosimilar to receive interchangeability status is granted one year of exclusivity. Therefore, other Humira interchangeable biosimilars, including Abrilada except Cyltezo, are restricted from labeling or other actions indicating interchangeability until June next year.

Exterior view of Samsung Bioepis building in Songdo, Incheon [Photo by Samsung Bioepis]

Jung Byung-in, Head of Regulatory Affairs (RA) Team at Samsung Bioepis, said, "We applied for Hadlima's interchangeability certification approval to expand patient access to our product in the U.S. We will continue to strive to realize the value of biosimilars that contribute to the sustainability of the healthcare industry." Jon Martin, Head of US Biosimilars at Organon, also stated, "Interchangeability approval is significant not only because it enables pharmacy substitution but also because it can enhance healthcare providers' confidence in prescribing biosimilars. We will continue to provide more patients with opportunities for treatment at more reasonable prices through biosimilars."

This content was produced with the assistance of AI translation services.