Recent advancements in technology have significantly impacted the drug development process. Increasingly advanced and powerful tools have shifted the focus of primary drug activation as well as which diseases are gaining attention.
Rare Diseases
Rare diseases have become a greater interest to manufacturers due to scientific advancements and regulatory incentives. The Orphan Drug Act has included incentives such as extended exclusivity periods, tax credits, and waiving of FDA fees, leading to a large number of drug approvals focused on rare diseases. These and other incentives have made rare diseases faster and more accessible to pursue, resulting in an explosion of interest from pharma. Advancements in genomics and bioinformatics have improved our understanding of the mechanisms of previously neglected diseases such as malaria and TB. While these diseases have not received as much attention in the past due to complexities in drug discovery, advanced technology has provided the opportunity for targeted therapies with longer market exclusivity and higher prices. Companies such as Pfizer, AstraZeneca, Merck, Ionis, Biogen, and many others are including rare diseases in their development pipeline.
Oncology
Oncology is a highly dynamic field, with regular breakthroughs that alter treatment pathways. Technology such as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) has contributed to these advances in understanding disease processes and potential sites of primary drug action. CRISPR allows scientists to alter genetic sequences with applications such as CAR-T therapy and engineering T-cells for individualized cancer treatment. This immunotherapy uses the patient’s own T-cells in treatments that have shown evidence of improving patient survival and reducing side effects. Even more recently, the number and scope of big pharma deals involving ex vivo gene therapy treatments have experienced a slackening, while in vivo gene therapies are beginning to come into their own right. This seems to be a natural progression of development given their extremely promising clinical merits, coupled with the CMC challenges involved in their execution.
Another rapidly changing area has been drug delivery methods. Traditional IV therapies are being supplanted by alternatives that offer numerous conveniences, with the newcomers often being easier to administer or requiring less frequent dosing. One of many recent examples that typifies this trend is the seven-minute “jab,” which is subcutaneous method of administering atezolizumab. Merck’s Keytruda was shown to be effective in a late-stage trial, with an even shorter intravenous time of 2-3 minutes. This makes it easier for providers to administer, which in turn drastically reduces the time that patients need to spend getting treated. The general trend is “to make existing oncology treatments better through formulation re-innovation,” in the words of Shorla Oncology’s Orlaith Ryan. Of course, the trending improvements in drug delivery methods haven’t been limited to the field of oncology, either. Chronic diseases that require constant management will no doubt be the biggest beneficiaries from these advances; everything from diabetes to long-term pain management could see big changes in the near future.
Early detection through genetic screening along with AI-guided technology can improve treatment outcomes by identifying cancer in an earlier, more easily treatable stage.
While the study of genomics focuses on the complete set of DNA, proteomics focuses on the structure, function, and interactions of proteins within an organism. This field provides insight into real-time biological processes by examining the molecular “machinery” in the cells compared to genomics, which is more of a “blueprint” of the cells. The field of proteomics is still limited but is expanding rapidly, fueled by its relationship with the equally young and burgeoning field of AI. The enormous amounts of data that can be collected and processed to show how protein interactions play out within living cells is a fertile avenue for AI research, with lots of advances still waiting – waiting for the deep dive that only AI can perform.
Neurodegenerative Disorders such as Alzheimer’s and Parkinson’s:
Another area of research that has benefitted from advancements in technology is the understanding of neurodegenerative disorders. Historically, this category of disorders has been hard to diagnose in early to mid-stages, and aren’t always recognized until later stages, when symptoms are more severe and treatments are less efficacious.
Distinct neurodegenerative disorders share many similarities, such as the presence of accumulated proteins that cause neuron death in areas of the brain. This can add to the challenge of a proper diagnosis, but also suggests the potential for a single drug to focus on these common pathways to address multiple diseases in a “basket” trial. Given the relatively low success rate of clinical trials for neurodegenerative diseases, the basket trial approach can help identify drugs that may be effective in other disorders based on commonalities. On a related note, platform trials, for which there is only one placebo arm and multiple active arms featuring different medications, also accelerate the pace of clinical trial development, making it possible to test medicines and formulations with far fewer participants needed for a successful comparison. This has led to an increase in the rate of research in neurodegenerative diseases, and has clear implications for accelerating drug development for rare diseases in particular.
One emerging therapeutic strategy is focused on mesenchymal stem cells (MSCs), which enable angiogenesis and tissue repair by influencing immune system responses. MSCs and their extracellular vesicles (EVs) show promise for treating neurodegenerative disorders due to their regenerative and anti-inflammatory properties. The EVs deliver bioactive molecules that support neural repair and modulate immune system activity.
MSCs can also be used as carriers for other treatments by using their ability to home in on tumors. They are drawn to tumors where they can then release treatment drugs directly at the site of the tumor. MSCs are drawn to tumors as a result of their chemokine receptors CXCR4 binding to stromal-derived factor-1(SDF-1), which is often at elevated levels around tumor sites.
