On October 30, we reported on the FDA’s decision to release a draft guidance that would obviate the need for late-stage, comparative efficacy studies for most biosimilar candidates. We brought up the question of timing, in that for some very high-profile biologic targets, phase 3 studies were already underway. The removal of a phase 3 trial requirement could cut development costs by up to $50 million and slash time to approval by three years.
What have manufacturers begun to do in the face of the draft guidance? Have they already taken steps to significantly pare the costs of their R&D program by shutting down a phase 3 trial that has begun or halt a phase 3 trial that is in the planning stages? For the major biologic drugs that are scheduled to go off patent in 2028 and beyond, this is a key question being wrestled with by manufacturers.
On the Pembrolizumab Biosimilar Development Front
According to data from ClinicalTrials.gov, some late-stage trials by manufacturers of other pembrolizumab biosimilar candidates have been suspended or terminated, though almost all of these decisions were implemented well before the FDA’s announcement. For example, Sandoz suspended its trial in May 2025, and Formycon did so in February 2025, the latter specifically based on consultations with the FDA.
Bio-Thera Solutions just initiated a phase 1 pharmacokinetics trial in September, but terminated its phase 3 clinical trial of BAT3306 in July 2025. On the trial page, Bio-Thera stated, “The new regulatory developments have led us to conclude that a Phase 3 study is no longer necessary for the development and approval of BAT3306. As such, to ensure effective use of clinical resources, we are terminating this study.”
Samsung Bioepis, however, is taking a different direction. The company disclosed that they have decided to move forward with their phase 3 trial of SB27, its Keytruda biosimilar candidate. This investigation was initiated in March 2024, and recruitment was completed this month. Study completion is expected in September 2026.
Anna Nayun Kim, a spokesperson for Samsung Bioepis, told BR&R, “Given the needs of [health care providers] and patients on clinical evidence for cancer therapies, we believe having robust clinical data from Phase 3 study on top of analytical, functional, and Phase 1 studies will help prescribers and patients have more confidence in biosimilars.”
She added, “As for our future biosimilar pipeline, we will be reviewing each molecule case by case, and will determine our clinical study design based on our thorough assessment of the reference product’s profile, relevant data, and whether analytical, functional, PK/PD and immunogenicity data will suffice to provide full scientific justification to waive a larger comparative clinical efficacy study for each molecule.”
Other manufacturers whose pembrolizumab biosimilar clinical trial programs are continuing (for now) include Celltrion, Amgen, and mAbxience. Henlius’ phase 3 trial was set to begin in April 2025, but it is not yet recruiting patients.
Developments on Nivolumab Biosimilar Development
For nivolumab biosimilars, with fewer announced candidates in the works, comparable activity is evident. Sandoz suspended its phase 3 trial of JPB898, stating on the study’s website “In light of the evolving regulatory landscape and growing indications that major Health Authorities will move towards a streamlined clinical development, Sandoz took a strategic decision and is [winding down its CJPB898A12301 clinical study.”
Amgen completed its phase 3 study of ABP 206 in October 2025, but another is currently ongoing, to be completed in January 2028.
mAbxience’s phase 3 study of MB11 was supposed to start last month (still listed as an estimated start date), with completion in April 2027.
Other potential groups, like Xbrane/Accord, appear to be in earlier stages of nivolumab biosimilar development, and may be tackling this decision right now.
The Science is Clear, but Will Clinicians Be as Accepting?
The science is clear that large phase 3 trials don’t add significantly to the clinical evidence of safety and efficacy of biosimilars. Yet it may be true that physicians particularly will be looking for some additional level of confidence a successful phase 3 trial may provide.
Certainly, we know that not all physicians and patients are sold on the therapeutic equivalence of biosimilars. I can hear the criticisms already from clinicians: “They weren’t tested in large, double-blinded trials, so we don’t know for sure that the biosimilar is clinically equivalent.” Could this give companies like Samsung Bioepis an advantage when launching its Keytruda biosimilar? There are tens of millions of dollars riding on that bet.
