Shots: 

• At the European Academy of Dermatology and Venereology (EADV) 2024 Congress, Biocon Biologics presented results from two pivotal P-III clinical studies. These studies supported the interchangeability between Humira and adalimumab-fkjp, as well as the biosimilarity between Bmab 1200 and Stelara for the treatment of patients with moderate-to-severe plaque psoriasis 

• In an engaging conversation with PharmaShots, Uwe Gudat, Chief Medical Officer (CMO) at Biocon Biologics, shared insights on the comparative efficacy, safety, and immunogenicity from the studies comparing adalimumab-fkjp with adalimumab and Bmab 1200 with Stelara 

• Uwe emphasized that the safety assessments confirmed that the safety specifications established for the respective reference biologics are equally applicable to adalimumab-fkjp and Bmab 1200 

Saurabh: Would you like to share the study design for the Phase III trials assessing Adalimumab-fkjp and Bmab 1200?  

Uwe: Both studies followed a multicentre double-blind randomised parallel-cohort design. Thereby they applied the methodology currently considered the gold standard in terms of clinical trial designs.  

In the study comparing Adalimumab fkjp to the matching reference biologic (RB) Humira patients with moderate to-severe plaque psoriasis were initially assigned to the RB. At week 12 patients were randomised in a balanced 1:1 ratio to either continue or be assigned to a multiple switch arm. In the switch arm patients were initially treated with Adalimumab-fkjp for 4 weeks (2 doses), then the RB for 4 weeks (2doses) before completing the study on Adalimumab fkjp. This design allows a direct and informative comparison between the continuous administration of the RB as opposed to using both therapeutics interchangeably. The study assessed the comparative efficacy, immunogenicity and safety associated with both the regimens.  

In the study comparing Bmab1200 to Stelara as the RB patients with moderate to severe plaque psoriasis were randomly assigned to either treatment in a balanced 1:1 ratio which they maintained for 12 weeks. Response to treatment at the end of the two-arm head-to-head comparison was the primary end-point of the study. Hereafter, patients initially allocated to the RB were re-randomised either to continue the RB or receive Bmab1200. Follow-up extended overall for 52 weeks. This design allows for a direct comparison of continued regimens of either Bmab1200 and the RB, as well as the impact of a single switch from the RB to Bmab1200. For all three treatment courses efficacy, safety and immunogenicity were recorded. 

Saurabh: In case of study assessing Adalimumab-fkjp, how did the low concentration biosimilar perform in comparison to the high concentration reference product? Can you elaborate on the PASI response in both switching and non-switching arms?  

Uwe: At the time the study was designed it was difficult to source Humira in the matching formulation as the reference biologic (RB). Endorsement was sought from the US Food and Drug Administration to use the readily available more concentrated formulation as a comparator. US FDA acknowledged the situation and accepted use of the more highly concentrated formulation for the comparison. Thus, the study directly compared both products in their respective formulations at dose parity.  

For a pharmaceutical agent it is implicitly the exposure that confers the treatment benefit. Exposure over time thus is generally considered to represent the independent variable and treatment effects the dependent variables that follow on. The direct comparison of the pharmacokinetic profiles of Adalimumab-fkjp and the RB in the respective formulations at dose parity from the study indicate that exposure to both does not differ in a meaningful way. Thus, bioequivalence was confirmed.  

Extrapolating from the established bioequivalence, it would thus be expected that the therapeutic benefits in terms of improvement in PASI score should not differ between the two arms. This was confirmed. At week 28 the mean (SD) PASI total scores were 1.64 (2.59) and 1.64 (2.53) in the continuous use and interchangeable use arms respectively. The mean changes from baseline were -19.86 (8.54) and -19.59 (8.81) accordingly.  

Saurabh: Given a positive outcome, how do you think the FDA “interchangeable” designation for Adalimumab-fkjp would affect its market position?  

Uwe: The results from this study provide evidence for health care professionals and other decision makers that adalimumab-fkjp and the RB when used in an interchangeable manner show a treatment profile that is indistinct from that of continuous use of the RB. This evidence reassures and gives confidence to the market that the two products as studied are interchangeable in clinical practice.  

Saurabh: Would you like to share the results of the phase 3 trial investigating Bmab 1200 in vs reference Ustekinumab for patients with Moderate to Severe Chronic Plaque Psoriasis?  

Uwe: The clinical trial comparing Bmab1200 against Stelera as the reference biologic (RB) in patients with moderate to severe plaque psoriasis confirmed that the two products provide efficacy, safety, tolerability and immunogenicity profiles that are indistinguishable as studied. The primary efficacy assessment change in PASI score showed no significant difference at 12 weeks. The consistency in PASI scores for the respective treatment arms was maintained thereafter. The safety and tolerability profiles showed no notable distinctions between the two products. The comparative assessment of immunogenicity also confirmed no notable difference between the two products in this respect. In conclusion, the study convincingly demonstrated that in a well-controlled randomized clinical trial the two treatments provide benefits that must be considered indistinct in daily practice. 

Saurabh: Like Adalimumab does the study assessing Bmab1200 will be assessing interchangeability?  

Uwe: As outlined above the study comparing Bmab 1200 with its RB followed a different design than the study comparing Adalimumab-fkjp to Humira. Both studies involved use of both treatments in a single patient in sequence. In the Adalimumab-fkjp study multiple exchanges were included. In the study with Bmab 1200 consistency in clinical findings was noted between Bmab1200 with the RB irrespective of a change in treatment. Thus, both studies provide compelling evidence that use of one or the other therapeutics adalimumab fkjp or its RB and Bmab 1200 or its RB in a single patient provide the same expectation of treatment effects, also when accounting for use of one of the other interchangeably. 

Saurabh: How did Adalimumab-fkjp and Bmab 1200 perform in terms of safety in comparison to their reference biologics?  

Uwe: A detailed assessment of the comparative safety profiles of Adalimumab-fkjp relative to its RB and the corresponding evaluation for Bmab1200 showed no notable differences in customary measures of safety and tolerability such as the occurrence of treatment emergent adverse events (TEAE), also when accounting for the assumed causal attribution to the exposure (events deemed related). This was confirmed in sub-group analyses when accounting for the presence of anti-drug antibodies. The assessments of safety confirmed that the safety specifications established for the respective RB are equally applicable for adalimumab-fkjp and Bmab 1200 as applicable. This evidence gives decision makers and users the confidence in both the products they are looking for.  

Image Source: Canva 

About the Author: 

Uwe Gudat 

Dr. Uwe Gudat is the Chief Medical Officer of Biocon Biologics and heads Clinical Development, Medical Affairs, Pharmacovigilance, and Drug Safety across geographies. Uwe joined Biocon Biologics in September 2023. He has over 10 years of experience in the biosimilars industry and has worked at leading global pharmaceutical companies for nearly 30 years. 

Uwe will be instrumental in driving Biocon Biologics’ clinical strategies, ensuring efficient progress of its products through clinical trials and regulatory approvals. In this role, he will also work closely with Biocon Biologics’ commercial teams across regions and provide them invaluable medical support and insights, thus contributing to the success of the Company’s commercialized products. 

Uwe will also be responsible for establishing key scientific relations with experts in the U.S. and EU, forming a strong advisory board for Biocon Biologics’ pipeline products. Additionally, he will oversee compliance and audit readiness in the areas of Pharmacovigilance and Clinical Development. 

A passionate advocate for technology, Uwe is also committed to scaling up activities for medical education and increasing patient outreach exponentially using social media. Uwe brings a wealth of experience to the Company. Before joining Biocon Biologics, Uwe served as Chief Medical Officer of Aretaeus Sarl, a drug discovery and development incubator focused on Type 1 and 2 diabetes mellitus and obesity. In a career spanning 28 years, Uwe has worked with leading global pharmaceutical companies such as Eli Lilly, Actelion, Novartis, Merck KGaA, and Fresenius Kabi. 

Uwe is an experienced clinician specializing in internal medicine, diabetes, and obesity. He also has extensive hands-on experience of working throughout the entire life cycle of both small molecules and biological entities across various therapeutic areas such as cardiovascular and metabolism, neuroscience, oncology, hematology, rheumatology, and immunology. 

He has expertise in the assessment of non-clinical data, development of efficient clinical strategies and dynamic research methodologies, clinical safety oversight, evaluation of clinical safety data, design, and compilation of dossiers (clinical sections), responding to queries from health authorities, and safety strategy encompassing Risk Management Plans (RMP) and Risk Minimization Measures (RMM). He also has experience in post-authorization medical product stewardship, including medical affairs and pharmacovigilance. 

Uwe holds an M.D. degree from the Philipps University in Marburg, Germany. He is licensed in internal medicine and sub-specialized in metabolic disorders. As a clinician, he trained under Prof. Michael Berger in Duesseldorf, Germany, at the WHO Collaborating Center for Diabetes Education. 

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