scholarly journals Scientific rationale underpinning the development of biosimilar rituximab in hematological cancers and inflammatory diseases

2019 ◽  
Vol 15 (36) ◽  
pp. 4223-4234 ◽  
Author(s):  
Wojciech Jurczak ◽  
Stanley Cohen ◽  
Timothy M Illidge ◽  
Antonio da Silva ◽  
Jutta Amersdorffer
Keyword(s):  
Inflammatory Diseases ◽  
Safety Evaluation ◽  
Development Program ◽  
Clinical Development ◽  
Biological Data ◽  
B Cell Depletion ◽  
Efficacy Evaluation ◽  
Clinical Development Program ◽  
Hematological Cancers ◽  
Totality Of Evidence

Sandoz rituximab (SDZ-RTX; Rixathon®; GP2013), a rituximab biosimilar, was approved in June 2017 in Europe in all indications of reference rituximab. The stepwise SDZ-RTX development program generated extensive physicochemical, structural, functional, and biological data demonstrating a match with reference rituximab on all clinically relevant attributes. A focused clinical development program followed, in two indications selected for sensitivity to detect potential differences versus reference rituximab: rheumatoid arthritis (pivotal pharmacokinetics and efficacy evaluation) and follicular lymphoma (pivotal efficacy/safety evaluation). These trials demonstrated highly similar pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity profiles. The totality of evidence for biosimilarity for SDZ-RTX, combined with knowledge that B-cell depletion is common to each approved indication, allowed SDZ-RTX approval for use in all indications of reference rituximab.

scholarly journals Edaravone in Amyotrophic Lateral Sclerosis’Lessons from the Clinical Development Program and the Importance of a Strategic Clinical Trial Design

US Neurology ◽  
2018 ◽  
Vol 14 (1) ◽  
pp. 47 ◽  
Author(s):  
Said R Beydoun ◽  
Jeffrey Rosenfeld
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Amyotrophic Lateral Sclerosis ◽  
Trial Design ◽  
Development Program ◽  
Clinical Trial Design ◽  
Clinical Development ◽  
Disease Heterogeneity ◽  
Clinical Development Program ◽  
Lateral Sclerosis

Edaravone significantly slows progression of amyotrophic lateral sclerosis (ALS), and is the first therapy to receive approval by the Food and Drug Administration (FDA) for the disease in 22 years. Approval of edaravone has marked a new chapter in pharmaceutical development since the key trial included a novel strategic clinical design involving cohort enrichment. In addition, approval was based on clinical trials that had a relatively small patient number and were performed outside of the US. Edaravone was developed through a series of clinical trials in Japan where it was determined that a well-defined subgroup of patients was required to reveal a treatment effect within the study period. Amyotrophic lateral sclerosis is associated with wide-ranging disease heterogeneity (both within the spectrum of ALS phenotypes as well as in the rate of progression). The patient cohort enrichment strategy aimed to address this heterogeneity and should now be considered as a viable, and perhaps preferred, trial design for future studies. Future research incorporating relevant biomarkers may help to better elucidate edaravone’s mechanism of action, pharmacodynamics, and subsequently ALS phenotypes that may preferentially benefit from treatment. In this review, we discuss the edaravone clinical development program, outline the strategic clinical trial design, and highlight important lessons for future trials.

Clinical Development of Antidepressive Drugs - the Viewpoint of the Industry

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
C. de Bodinat ◽  
B. Delalleau
Keyword(s):  
Depressive Disorders ◽  
Rating Scale ◽  
Development Program ◽  
Placebo Response ◽  
Clinical Development ◽  
Short Term ◽  
Double Blind ◽  
Clinical Development Program ◽  
Term Efficacy ◽  
Number Of Patients

The clinical development program strategy of a new treatment of depression to be registered in Europe must be built in agreement with recommendations of the CHMP guidance.Demonstration that an antidepressant is effective in treatment of major depressive disorders requires consideration of specific recommendations notably regarding the use of placebo and reference drugs, efficacy assessment, designs features and safety aspects.In the field of depression, comparisons between test medicinal product and reference drugs are difficult to interpretate since the level of placebo response is high and variable. An adequate evaluation of antidepressant efficacy is firstly based on randomised double blind comparison versus placebo. For short term efficacy, studies with 6 week-treatment period are required and three arm trials including placebo and active control are recommended. Regarding the long term efficacy, relapse prevention study is the design recommended for demonstrating that the short term effect can be maintained over time.Assessment of efficacy criteria includes both clinical relevance and statisitical significance, particularly:Improvement expressed as difference between baseline and post-treatment score in symptomatology and as proportion of responders.Remission, defined as a condition where no or only few signs remained, with a justified cut-off on a validated rating-scale.In randomised withdrawal trials, efficacy is expressed as number of patients relapsing and/or time to relapse.The acceptable scales for use as primary endpoint include the HAM-D17 scale, the MADRS scale. Cautions regarding designs features, safety assessment and the global methodological issues faced in conducting such program will be detailed in the presentation.

Hepatic safety and tolerability in the maraviroc clinical development program

AIDS ◽  
2010 ◽  
Vol 24 (17) ◽  
pp. 2743-2750 ◽  
Author(s):  
Ayman Ayoub ◽  
Sam Alston ◽  
James Goodrich ◽  
Jayvant Heera ◽  
Andy IM Hoepelman ◽  
...  
Keyword(s):  
Development Program ◽  
Clinical Development ◽  
Clinical Development Program
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