Precision medicine and biologics hold the key to better therapeutic outcomes in patients: Dr C N Ramchand, MagGenome

Shahid Akhter, editor, ETHealthworld , spoke to?Dr C N Ramchand, Co-founder, CEO & CSO, MagGenome Technologies, to find out the latest protocol in the management of various diseases by combining precision medicine and biologics.

The Idea behind AMDP

Advances in Molecular Diagnostics and Precision Medicine (AMDP 2022) was organized at Chennai, at Anna University and associate partners are SciGenom and Scigenom Research Foundation. The Idea behind the AMDP conference is to bring together Nobel Laureates, accomplished physicians, oncologists, molecular biologists, and various other scientists, students, nationally and internationally on a single platform over three days of the conference to share their research and findings for the benefit of the larger group. The conference also has poster presentation sessions by science students as well as business pitching sessions by start-up companies throughout the conference.

Precision Medicine

The Genesis of modern medicine or allopathy started around 100 years back. For the first 50 years, we have had New Chemical Entities (NCEs) that produced around 400 plus therapeutic molecules for various ailments. So over the early 50 years, the drug molecules were developed based on serendipity and phenotypic changes observed by doctors. Post this around the 1960s, rational drug development started and is seen even now. Towards the 1980s, novel biologic products were developed based on molecular biologic techniques from scientifically identified proteins.

Intuitive therapy

From 1950 onwards, the few molecules that were developed were based on intuitive therapy – this is where the doctor's observed phenotypical changes in the signs and symptoms of the patient being treated with the medicine. This went on till the 1970s.

Evidence-based therapy

After that, saw the rise of the clinical evidence-based drug development process, where the drug was not approved for use by the regulatory body till there was clinical evidence that showed that at least 70% of the patients improved because of the efficacy of the therapeutic molecule. During this clinical evidence-based drug development process, the doctors and regulatory authorities noticed that most of the new chemical entities showed between 50% to 80% benefit in the patients treated with the drug. Therefore, they came up with the mandate that the new investigational drug will have to show at least 70% efficacy to get approved. This also meant that the approved molecules during that time showed no significant improvement in 30% of the patients.

This brought about the need to understand the pharmacogenomics of new chemical entities or small molecules. This led to the learning that there are four important points that the drug needs to get transported within the cellular level to show its efficacy. At any of these points if the drug does not meet the cellular transport requirements the drug is considered ineffective. The learnings that the scientists got during this phase is that once the drug gets into the bloodstream, if it does not bind to the appropriate proteins in the serum or if it binds too much, drug absorption gets affected, failing the drug. The third important part of the drug transport is associated with the Cytochrome P450 or liver enzyme metabolism. At this stage if the liver does not metabolise the drug and excrete it out from the body, the drug will accumulate in the body and become toxic, similarly, if the drug is metabolised very fast, it loses its efficacy. The 4th?important understanding associated with drug efficacy is the point that if the protein receptor that has to bind with the drug is mutated, the drug will become ineffective.

Mutated Gene

With the understanding that drug efficacy is mainly dependent on the proteins that bind to the drug to make it effective, a mutated gene or single-nucleotide variant (SNV), which affects the protein will also affect the drug.

Bilogics

Precision medicine is mainly associated with the use of biologics, especially in the case of cancer management. One of the examples that can be quoted is associated with EGFR mutation in the case of non-small cell cancer the drug may not be effective. In the same way, in the case of cholesterol-reducing statins, if there are mutations in HMG co-reductase, there will be efficacy issues.

Therefore, the way forward in such cases is to identify the genome of the patient using next-generation sequencing which will provide information to the treating physician about the type of drug that has to be used to treat a patient effectively. This is also called personalised therapy.

Precisicion medicine and biologics

While modern medicine has been evolving over the last few years, we have been able to understand that out of the 35,000 human diseases that are identified, there are around 2,000 protein targets, and 400 new molecules that are used for the management of various diseases. Over the last 20-30 years around 40-50 biologics and antibodies have been developed for the management of select diseases.

The future is mainly a combination of precision medicine and biologics that can be used for better therapeutic outcomes in patients.