On October 15, 2021, the FDA approved Boehringer Ingelheim’s Cyltezo® (adalimumab-adbm) as interchangeable with AbbVie’s Humira® (adalimumab) for many of Humira’s approved indications. As an interchangeable, Cyltezo can be automatically substituted for Humira at the pharmacy, subject to individual state laws. Grant of interchangeability status was based on the phase III VOLTAIRE-X study, which evaluated switching patients with moderate-to-severe chronic plaque psoriasis between Cyltezo and Humira and back again, and found that those who switched had similar clinical outcomes in terms of safety, efficacy, pharmacokinetics, and immunogenicity to those who did not switch.
Cyltezo was initially approved as a U.S. biosimilar in August 2017, but it, along with the five other approved Humira biosimilars, has not yet launched. Under a settlement agreement between AbbVie and Boehringer Ingelheim, Cyltezo can launch in the U.S. as of July 1, 2023. According to the other settlement agreements, the soonest a Humira biosimilar will launch in the U.S. is Amgen’s Amjevita™ (adalimumab-atto) on January 31, 2023.
Cyltezo is the second drug to be granted interchangeable status in the U.S., following Viatris and Biocon’s Semglee® (insulin glargine-yfgn), which was approved as an interchangeable biosimilar to Sanofi’s Lantus® (insulin glargine) in July 2021. Cyltezo is the first monoclonal antibody to achieve interchangeable status in the U.S.
While finally having a biosimilar receive interchangeability status for one of the highest grossing drugs in the U.S. is very encouraging for patients, Cyltezo is approved as a low-concentration adalimumab (40mg/0.8mL, 20mg/0.4mL dosage strength), usage of which accounts for only about 10% of total adalimumab usage. Therefore, only a small portion of patients will likely see the benefit of the lower cost of the interchangeable once it launches.
Currently, there is one pending aBLA for a high-concentration (100mg/mL) Humira biosimilar, AVT02, filed by Alvotech. Alvotech also plans to seek an interchangeability designation for AVT02 based on results from its switching study AVT02-GL-302. AbbVie and Alvotech are involved in three pending litigations (Case Nos. 1:21-cv-02899 (N.D. Ill.), 1:21-cv-00589 (E.D. Va.), and 1:21-cv-02258 (N.D. Ill.)), and while Alvotech has stated it will launch its biosimilar at-risk, it has agreed not to launch until after a district court decision in these cases, which is slated for the end of October 2022.