Harnessing genetics to propel cancer research and clinical success

When navigating the landscape of pharmaceutical development, clinical trials represent both a crucial checkpoint and a formidable barrier. Industry studies show that approximately 90% of drugs entering clinical development do not achieve regulatory approval. For oncology drugs, the failure rates are particularly notable, with only 57.6% of drug candidates progressing from Phase I to Phase II, and just 32.7% advancing from Phase II to Phase III, according to the American Council on Science and Health.

For single-asset companies pioneering the exploration of innovative therapeutics through a pipeline-in-a-product strategy, these statistics have profound implications, mandating a need to strategically enhance the chances of success. One way is through the utilisation of genetic insights.

Leveraging genetic pathways: Clinical trial risk reduction

Understanding and leveraging genetic pathways early in drug development is crucial in today’s investment environment, where capital flows towards the most scientifically robust ideas and teams. This approach not only aligns companies with cutting-edge scientific advancements, but also builds investor confidence by demonstrating a proactive stance towards reducing clinical trial risk. For example, Step Pharma is exploring an innovative therapeutic target that is genetically validated. Specifically, we are focusing on the enzyme CTPS1, a target whose significance is underscored by rigorous genetic research demonstrating the role CTPS1 plays in lymphoproliferative diseases. Identifying such specific targets allows therapeutic approaches to be tailored more precisely, helping to increase the chances of success in clinical trials.

Genetics have revolutionised approaches to cancer treatment by revealing the molecular underpinnings of the disease. Precision medicine, for example, has demonstrated significant success rates. Drugs developed with a genetic basis have a higher probability of clinical trial success and approval compared to non-genetically based therapies. According to a study reported by the Biotechnology Innovation Organization, drugs developed with biomarkers, which can include genetic markers, have an approval rate that is more than three times that of drugs developed without them - historically, this rate is about 25.9% versus 8.4% for those where no selection biomarkers were used. This stark difference highlights the importance of genetic research and its application in drug development.

Targeted therapies designed to exploit specific genetic anomalies in cancer cells, such as the BRAF V600E mutation in melanoma, have led to remarkably effective treatments. By precisely targeting the altered protein, treatments like vemurafenib have significantly improved outcomes for patients with metastatic melanoma and other cancer types harbouring this mutation, showcasing the power of genetic-based strategies. These advancements are not only promising, but also critical, as they pave the way for more personalised and effective treatment options.

Furthermore, the concept of synthetic lethality, where functional loss of two separate genes is lethal, but inhibition of each gene in isolation has no effect, provides a blueprint for developing therapies that specifically kill cancer cells while sparing healthy ones. Leveraging genetic insights to identify these tumour-specific synthetic lethal pairs enhances the efficacy of treatments, whilst significantly reducing adverse effects and increasing the tolerability of therapies. This innovative approach to treatment design underscores the potential of genetic research in creating precision cancer therapies.

Genetics for drug development success

By identifying specific genetic biomarkers, we can understand the mechanism of action and be guided in selecting the right patients for clinical trials. This tailored approach has the potential to enhance the effectiveness of the treatment and improve its safety profile, substantially increasing the likelihood of clinical success. A precision approach to patient selection ensures that therapies are both effective and safe, minimising unnecessary exposure to those unlikely to benefit.

The evidence is clear: integrating genetics into drug development not only enhances the efficacy of treatments, but also significantly increases the likelihood of clinical and regulatory success. By adopting genetic approaches and developing assays to detect tumour specific changes, we can mitigate the risks associated with clinical trials, optimise therapeutic outcomes, and ultimately accelerate the delivery of innovative treatments to patients. As we advance our understanding of the genetic basis of cancer, embracing these strategies will undoubtedly transform the treatment landscape, offering new hope and better therapies to those living with cancer worldwide.

The role of genetics in cancer research and treatment cannot be overstated. The ability to understand the genetic makeup of tumours and develop targeted therapies accordingly represents a significant leap forward in oncology. By continuing to invest in genetic research and applying these findings to our drug development processes, we aim to bring new, effective, and safer treatments to patients who need them most. The future of cancer treatment is undoubtedly tied to our ability to decode and combat the genetic factors that drive this complex disease.