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The proposed overhaul of the U.S. drug approval system through the 21st Century Cures Act won’t take us back in time. With the right safeguards in place, this legislation can help win the fight against Alzheimer’s, Ebola and many other diseases. It seems like the much awaited prescription for patients as well as the industry.
Development of pharmaceutical drugs can be time-consuming and extremely expensive. The last industry-funded research estimated the cost of developing each new drug at US $ 2.6 billion.
The losing fight against Alzheimer’s
On top of the high cost of development, the failure rate can be quite high. Take the case of Alzheimer’s disease. Since 1998, over 120 programs attempting to develop Alzheimer’s drugs have failed. Between 2002 and 2012, there was just a 0.04 percent success rate of Alzheimer’s drugs meeting the standard.
Last week, the fight against Alzheimer’s received yet another setback. US-based Biogen’s biotech drug, Aducanumab, was hailed as a potential breakthrough in March when it became the first Alzheimer's treatment to significantly slow cognitive decline.
However, new data published by Biogen last week revealed that Aducanumab failed to significantly slow mental decline, thereby tempering the great expectations the world had from this potential drug.
Enter the 21st Century Cures Act
Clearly, the new drug development process needs to change. On July 10, the U.S. House of Representatives approved the 21st Century Cures Act. The Act seeks to modernize clinical trials and deliver better, faster cures to more patients. The Act is awaiting approval in the Senate.
However, several provisions of the proposed act have come under severe criticism. For instance, in The New England Journal of Medicine, Jerry Avorn, M.D., and Aaron S. Kesselheim, M.D., J.D., M.P.H., say “if enacted into law, some of its provisions could have a profound effect on what is known about the safety and efficacy of medical products, as well as which ones become available for use.”
Biomarker based drug approval
The proposed Act encourages biomarker-based drug approval. Unlike conventional drug approvals, which involve extensive clinical trials, where outcomes are studied in patients, the biomarker-based approach works on studying a “surrogate marker”, which is strongly linked with the final outcome in the patient.
“A commonly used example is cholesterol. While elevated cholesterol levels increase the likelihood for heart disease, the relationship is not linear – many people with normal cholesterol develop heart disease, and many with high cholesterol do not.
‘Death from heart disease’ is the endpoint of interest, but ‘cholesterol’ is the surrogate marker. A clinical trial may show that a particular drug (for example, simvastatin) is effective in reducing cholesterol, without showing directly that the drug prevents death.”
The bill would encourage the FDA to rely more on biomarkers and other surrogate measures rather than actual clinical endpoints in assessing the efficacy of both drugs and devices.
The biomarker-based drug approval has also generated its fair share of concerns since “a drug's effect on a biomarker can make approval quicker and less costly, especially if the comparator is placebo, it may not always predict the drug's capacity to improve patient outcomes”
But the key point to note is that the FDA already uses surrogate endpoints in about half of the new drug approvals. The legislation would not immediately change FDA approval standards, but they would give the agency greater discretion to approve drugs on the basis of less comprehensive data.
Accelerated approvals have been in place since 1992
The FDA has had an Accelerated Approval (AA) program in place since 1992. This has already been used extensively in oncology and HIV drugs.
And the AA programme has benefited patients. As per an FDA presentation, almost 90 percent of the drugs approved for oncology through the AA process demonstrated a benefit in the post-market study. Since 1995, 49 new drug indications have been launched. In the case of HIV drugs, all indications that were given accelerated approval also received regular approval.
For something as dangerous as Ebola, where there still isn’t an approved treatment to contain the spread of the Ebola virus, computational models have been used to evaluate existing drugs. Over 50 FDA approved drugs have now been identified with activity against the Ebola virus.
Will it not be wise to use them in the fight against Ebola?
Need for vigorous safety monitoring
The essence of the proposed 21st Century Cures Act is positive. Increased and faster drug approvals is great news for patients and the industry. What is needed are the right measures and safeguards to ensure the drug approvals (based on biomarkers) are not ‘free for all’ and there isn’t an unfettered access of such drugs to a large population.
More importantly, the proposed act will increase safety monitoring. This means drug developers will have to monitor patients more vigorously using devices, such as smartphones. If drugs get approved based on biomarkers, the smartphone should be leveraged as an integrated health tool that sends feedback on how patients are performing after a drug is administered.
Our View
There are several smartphone applications available today. For instance, Apple’s ResearchKit allows developers to monitor multiple healthcare outcomes like asthma occurrence, determine the progress of Parkinson’s, share information about the effects of chemotherapy used in breast cancer and also measure gait and balance.
Supportive legislation coupled with Apple and Google aggressively getting into the healthcare space, it is just a matter of time before the digital health revolution joins our fight against diseases to benefit patients as well as the industry.
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Image Credit : End Century by kevin dooley is licensed under CC BY 2.0
“ The article is based on the information available in public and which the author believes to be true. The author is not disseminating any information, which the author believes or knows, is confidential or in conflict with the privacy of any person. The views expressed or information supplied through this article is mere opinion and observation of the author. The author does not intend to defame, insult or, cause loss or damage to anyone, in any manner, through this article.”
