Emerging social problems or opportunities can significantly impact the funding available for the development of drugs for specific diseases. When COVID-19 ravaged the world, funding from Operation Warp Speed led to vaccine development in record time. Public awareness campaigns, such as the ALS ice bucket challenge, can also directly raise money for research. This viral social media campaign generated nearly $90 million in research funding for 237 scientists from 2014 to 2018; This led to new clinical trials and the discovery of five genes linked to amyotrophic lateral sclerosis, commonly referred to as Lou Gehrig’s disease.
How does science approach drug development?
To create breakthrough treatments, researchers need a basic understanding of which disease processes they need to cure or prevent. This requires the development of cell and animal models that can simulate human biology.
It can take many years to study potential treatments and develop a finished drug product ready for testing in humans. After scientists identify a potential biological target for a drug, they use high-throughput screening to quickly evaluate hundreds of chemical compounds that may have the desired effect on the target. They then modify the most promising compounds to increase their potency or reduce their toxicity.
When these compounds have inconclusive results in the laboratory, companies are likely to halt development if the estimated potential revenue from the drug is less than the estimated cost of improving treatments. Companies can charge more for drugs that significantly reduce death or disability than for drugs that only reduce symptoms. Researchers are also more likely to continue working on drugs that have a greater potential to help patients. To gain FDA approval, companies must ultimately show that the drug does more good than harm to patients.
Sometimes researchers know a lot about a disease, but current technology is insufficient to produce a successful drug. Scientists have long known that sickle cell disease is caused by a defective gene that causes cells in the bone marrow to produce poorly formed red blood cells, causing severe pain and blood clots. Scientists have not found a way to solve the problem or find a solution to this problem with existing methods.
But in the early 1990s, basic scientists discovered that bacterial cells had a mechanism to identify and edit DNA. With this model, researchers began the painstaking work of developing a technology called CRISPR to identify and edit genetic sequences in human DNA.
Technology has finally advanced to the point where scientists can successfully target the problematic gene in sickle cell patients and edit it to produce normally functioning red blood cells. In December 2023, Casgevy became the first CRISPR-based drug approved by the FDA.
Sickle cell disease presented a major target for this technology because it is caused by a single genetic problem. It was also an attractive disease to focus on because it affects approximately 100,000 people in the United States and is costly to society, causing many hospitalizations and lost work days. It also disproportionately affects Black Americans, a population that is underrepresented in medical research.
Real-world drug development
To put all these pieces of drug development into perspective, consider the leading cause of death in the United States: cardiovascular disease. Although several drug options are available for this condition, there remains a need for more effective and less toxic medications that reduce the risk of heart attack and stroke.
In 1989, epidemiologists found that patients with high bad cholesterol (LDL) had more heart attacks and strokes than those with low cholesterol levels. Currently, 86 million American adults have high cholesterol levels that can be treated with medications such as the popular statins Lipitor (atorvastatin) or Crestor (rosuvastatin). But statins alone cannot help everyone reach their cholesterol goals, and many patients develop unwanted symptoms that limit the dose they can take.
Therefore, scientists have developed models to understand how LDL cholesterol is formed in the body and how it is eliminated from the body. They found that LDL receptors in the liver remove bad cholesterol from the blood, but a protein called PCSK9 destroys them prematurely, raising levels of bad cholesterol in the blood. This led to the development of drugs Repathy (evolocumab) and Praluent (alirocumab), which bind to PCSK9 and stop it from working. Another drug, Leqvio (inclisiran), blocks the genetic material that codes for PCSK9.
Researchers are also developing a CRISPR-based method to treat the disease more effectively.
The future of drug development
Drug development is driven by the priorities of funders, whether governments, foundations, or the pharmaceutical industry.
Based on the market, companies and researchers tend to study highly common diseases with devastating societal consequences, such as Alzheimer’s disease and opioid use disorder. But the work of advocacy groups and foundations may increase research funding for other specific diseases and conditions. Policies such as the Orphan Drug Act also create successful incentives for the discovery of treatments for rare diseases.
But in 2021, 51% of drug discovery spending in the US was directed to just 2% of the population. One issue is how to strike a balance between providing incentives to develop miracle drug treatments for the few at the expense of the many. It’s a question researchers and policymakers are still grappling with.
This article is republished from The Conversation, an independent, nonprofit news organization providing facts and analysis to help you understand our complex world.
Written by: C. Michael White, University of Connecticut.
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C. Michael White does not work for, consult for, own shares in, or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond his academic duties.