A Case Study in Clinical Efficacy and Toxicity: Bintrafusp Alfa 💊 

By Imagine Biotech

If you are interested in drug discovery story, you’ll enjoy this one…

Bintrafusp Alfa

Bintrafusp Alfa showed great promise. With encouraging results from pre-clinical and Phase 1 clinical trials, the stage was set for Bintrafusp Alfa, a lung cancer drug developed by Germany’s Merck. The drug garnered significant attention, with many believing it could surpass Keytruda as the leading treatment for late-stage lung cancer. This optimism was further validated when GSK struck a deal with Merck, investing $360 million upfront, with the potential for the agreement to reach $4.2 billion upon achieving milestones and producing a marketable product. Despite the initial excitement and substantial investment, the endeavor ultimately did not succeed.

In later-stage clinical trials, a significant number of individuals receiving Bintrafusp Alfa had to discontinue treatment due to adverse effects related to the therapy. The Objective Response Rate (ORR) — which measures the percentage of individuals experiencing partial or complete response to a treatment, typically in terms of tumor shrinkage or reduction in cancer cells — was a mere 10.1%.

The Deal Breaker

Faced with these disappointing efficacy and toxicity results, both investors and scientists found themselves empty-handed. The deal between GSK and Merck eventually fell through but Merck continued research into the drug which has since shown some signs of improvement, but nothing near what was expected initially heading into clinical trials. Bintrafusp Alfa was put to the test against the current reigning champion in late state lung cancer therapy: Keytruda.

During the process of development for an alternative therapeutic, clinical efficacy and safety must dominate. If a new drug is no more effective, and especially if the drug is less safe in comparison to a previous drug, there is little chance that the drug will make it to market, and even if it did, whey would a doctor prescribe it? Hint: They wouldn’t.

Preclinical Studies in Regard to Bintrafusp Alfa 🐁 

Positive Pre-Clinical Studies

One significant driving factor in the hype regarding Bintrafusp Alfa was positive preclinical studies, specifically in regard to efficacy in murine (mouse) models. In rodents, Bintrafusp Alfa effectively suppressed tumor growth and metastasis more effectively when compared to other, previous therapeutic techniques.

While these studies were initially undertaken prior to 2016, when clinical trial screening began, a paradigm shift in regard to toxicology studies and non-rodent studies has occurred. In December of 2022, the FDA Modernization Act 2.0 was signed into law. This bill essentially negated portions of Federal Food, Drug, and Cosmetics Act of 1938 which required animal testing for new drug development protocols. While animal lovers rejoiced, some were skeptic until the FDA released a statement ensuring that safety was still priority in drug development.

“Product developers must show the FDA that a medical product is reasonably likely to be safe for testing in people. Only scientifically reliable and validated test methods can be used to show product safety before testing in people.” - U.S. Food and Drug Administration

Cost of Animal Testing

The costs of animal testing are significant. Basic toxicology studies with mice, including single-dose tests, range from $50,000 to $200,000. Repeated dose toxicity tests can cost $200,000 to $500,000. Non-rodent studies, using dogs and monkeys, are even more expensive. Short-term toxicology studies range from $500,000 to $1,000,000, and long-term studies exceed $1,000,000. 

Given this investment and the fact that animal testing isn't always required in preclinical trials, one might wonder if investing in ADMET testing and pharmacokinetic modeling of Bintrafusp Alfa could have revealed toxicity earlier.

This could have redirected resources toward developing a more promising therapeutic. This challenge is what Imagine Biotech aims to address.

The Capital Investment 💵 

Poor clinical trial results are detrimental to all parties involved. Patients miss out on potential therapeutic alternatives that could address their chronic ailments. Pharmaceutical companies, having invested substantial time, money, and intellectual resources into drug development, find themselves with nothing to show for their efforts. Investors and founders, are often left questioning whether these setbacks could have been avoided through more diligent preclinical studies.

The Imagine Biotech Solution 🔬 

Imagine Biotech resources can call upon a wide variety of technologies to de-risk your portfolio using sophisticated pathways that have matured due to improved data resources, confounding factors, and improved model assumptions.

Our array of services range from sophisticated molecular modeling density functional methods (DFT) to the first-of-its-kind integration package of ADMET and PK predictions to academic risk.

Imagine Biotech staff have the training, expertise, and knowledge to review the proposed hypotheses (investment) in their entire journey to commercialization and select those tests/technologies to support further investment success or flag issues that arise only in the environment of review by skilled biotechnology experts.

We believe that informed investments are the cornerstone of progress. Our mission is to empower investors with the insights and tools necessary to navigate the complexities of biotech investments with confidence.