Q&A with CAS Managing Director Todd Wills
Todd Wills, Managing Director, Consulting Services at CAS, talked to Med Ad News about what COVID-19 has taught us about pharmaceutical R&D; insights and predictions on future drug approval trends; and other topics.
By Andrew Humphreys • [email protected]
Med Ad News: Which structurally novel drugs from the FDA’s 2020 approval list are most notable?
Todd Wills: Small molecules continued to be an important drug modality in 2020, as they once again represented almost 70 percent of the approved new therapeutic drugs (not including diagnostic imaging agents). At CAS we have been looking at small-molecule drug innovation through the lens of structural diversity. Most of this year’s approved small-molecule drugs included at least one new molecular entity (NME) that was based on a new chemical shape.
Likely the new drug that will get the most attention, for obvious reasons, is Veklury (aka, remdesivir). It was the first treatment for COVID-19 to receive FDA approval, and is a structurally novel drug based on its molecular shape.
Some other notable structurally novel drugs approved in 2020 include precision oncology therapies such as Orgovyx (relugolix), which is the first precision oral treatment for patients with advanced prostate cancer, Pemazyre (pemigatinib), which is the first targeted treatment for patients with cholangiocarcinoma, a cancer of bile ducts, and Tabrecta (capmatinib), the first targeted treatment for patients with metastatic non-small cell lung cancer that have a mutation leading to MET exon 14 skipping. Overall, structurally novel drugs have been making a significant contribution to the notable uptick in precision oncology drug approvals in recent years.
Gene-specific therapies is another area where a lot of structurally innovative drugs are making significant impact. Some examples from this year include Evrysdi (risdiplam), the first oral drug approved to treat spinal muscular atrophy (SMA), and Retevmo (selpercatinib), the first therapy for patients with lung and thyroid cancers with the RET (rearranged during transfection) gene alterations.
Med Ad News: Why is structural innovation in drug discovery paramount to future breakthroughs and blockbusters?
Todd Wills: Based on CAS analysis, structurally novel drugs are more than twice as likely to be designated as a breakthrough therapy by the FDA and far more likely to achieve blockbuster status (i.e., more than $1 billion in annual revenue within five years of launch) than drugs that have the same shape as a previously approved drug. Thus, structurally novel drugs have a dramatic impact on improving public heath, and also provide significant commercial benefits to their developers.
Med Ad News: What has COVID-19 taught us about pharmaceutical R&D and how can we transfer those learnings to drive faster progress in other diseases?
Todd Wills
Todd Wills: The search for COVID-19 vaccines and therapies has fostered an unprecedented level of collaboration among industry, academia, and government organizations. This sharing of data and insights provided the research community with better and faster access to existing and emerging data in order to accelerate their research efforts. Some examples of these collaborative initiatives include
• Global Initiative on Sharing Avian Influenza Data (GISAID) = genome sequencing data
• COVID-19 Open Research Dataset (CORD-19) = full text of COVID-19 related scientific literature
• CAS COVID-19 dataset = open dataset of structures of antiviral drugs and substances that are structurally similar to known antivirals
If greater collaboration is able achieve these results in a crisis, it begs the question if it could also accelerate progress against other major diseases. I do wonder if a more robust co-opetition model might produce better results than competition from a public health, and possibly a commercial, perspective and what would be required fundamentally to facilitate that more broadly.
Med Ad News: What are some of your insights and predictions on future drug approval trends?
Todd Wills: COVID-19’s adverse impact on clinical trials unfortunately may translate to a reduced number of new drug approvals in 2021 as the pipeline of new drug candidates approaching the regulatory review phase experiences a temporary decline.
With structurally novel, small-molecule drugs demonstrating outsized public health and commercial benefits, the need to more quickly explore the vast remaining uncharted areas of chemical space for new drug candidates is clear. This represents a tremendous opportunity for those seeking cures for the world’s most challenging diseases; however, figuring out which areas offer the greatest potential for a particular therapeutic need remains a critical challenge. I anticipate that on-going advancements in the application of machine learning to drug discovery will increase the speed and efficiency with which researchers can explore larger candidate pools and thus lead to more new drugs, and specifically more structurally novel drugs, in the coming years. The growing application of in silico approaches as part of pharma innovation pipelines is increasing demand for high-quality chemical substance data, including structure activity relationships, and driving advancements in cheminformatics technologies. For example, we are currently working with a number of organizations on using molecular representations customized for a specific use case to greatly improve the accuracy of algorithms that predict things like bioactivity.
