CinnaGen-Related Clinical Studies Questioned by Preprint, Putting Biosimilar Evidence Chain Under Renewed Scrutiny

In the biosimilar market, price accessibility and clinical trust are often weighed on the same scale. If a drug is to replace an expensive originator biologic, it must rely on rigorous, transparent and reproducibly testable evidence to convince physicians, patients and regulators. Once the research process itself is questioned, what is affected is not just one paper, but the reliability of the entire evidence chain.

A preprint posted on arXiv on May 12 examined 23 randomized trials and post-marketing studies linked to Iranian biosimilar manufacturer CinnaGen and its associated company Orchid Pharmed. Using the INSPECT-SR research integrity framework, the authors reported 180 issues across trial registration, outcome presentation, study design, numerical calculations and statistical analysis, and described the pattern they observed as “clinical trial engineering.”

The core of the allegation is not whether a single data point is wrong, but whether multiple studies show repeated and directional abnormalities. According to the abstract, the analysis covered randomized assignment and post-marketing data, indicated that some studies may have inconsistencies between registration information and formal reports, and also noted that tables, sample sizes, arithmetic and statistical results require checking. If these problems are substantiated, readers of the studies would find it difficult to judge whether differences in efficacy and safety came from real clinical observations or from bias in study design and reporting processes.

However, the article is currently still a preprint that has not undergone peer review, and there do not yet appear to be independent, credible external sources on the same matter that have verified its item-by-item findings. This means the relevant conclusions should be regarded as a serious research integrity warning signal, rather than a finalized judgment of misconduct. For CinnaGen, Orchid Pharmed and the relevant research teams, the key issue will be whether they can publicly respond to specific items and provide raw data, trial registration records and statistical analysis workflows for third-party review.

The clinical development of biosimilars is inherently different from that of traditional new drugs. It usually does not aim to prove a molecule’s entirely new efficacy again, but to demonstrate that the candidate product has no clinically meaningful differences from the approved reference drug in quality, immunogenicity, pharmacokinetics and clinical effects. For that reason, research transparency and methodological consistency are especially important. Seemingly small registration changes, analysis switches or numerical contradictions can all grow into questions of trust.

Such questions also remind readers that the strength of clinical evidence depends not only on whether a study is published or randomized, but also on whether the research question was clearly defined in advance, whether the data are complete and traceable, and whether the statistical methods conform to the original plan. The value of frameworks such as INSPECT-SR lies precisely in moving the focus of interpretation from the conclusions back to the research process itself, so that systematic reviews not only synthesize results but can also identify cracks in data credibility.

The most cautious reading at present is this: the preprint raises signals that need to be taken seriously, but journal review, independent replication and responses from the parties involved are still needed to clarify them. If subsequent verification supports its findings, the evidence base and review records for related products may face deeper questioning. If some allegations are corrected or overturned, that will also help define the boundaries of research integrity tools in the assessment of clinical literature.