Fast-Tracked Drugs are Crossing the Finish Line Safer

The Food and Drug Omnibus Reform Act of 2022 (FDORA) includes key revisions that heavily impact the FDA-regulated industry. The act demonstrates substantial potential in ameliorating the treatment of rare diseases through the accelerated approval pathway. As 2023 comes to a close, we begin to see how FDORA has changed the landscape of accelerated drug development for Americans in its first year.

The accelerated approval program was created in 1992 to expedite the approval of non-opioid drugs that show promise in an area of unmet medical need. The advantage of fast-tracking is that patients can receive these drugs significantly faster. This benefit, however, comes with a cost; due to the streamlined timeline, pharmaceutical companies are not required to provide rigorous evidence of the drug’s clinical success as they are with traditional approval. Instead, companies submit a data point that implies future success; as such, drug makers need not prove efficacy, but rather predict it. Because accelerated approval has a lower standard of evidence than traditional approval, a confirmatory trial is required to confirm that the drug is indeed effective.

Alarmingly, 112 of the 253 drugs approved through the accelerated approval pathway still have not been confirmed as clinically effective in post-approval studies. The issue lies in companies failing to promptly conduct confirmatory trials without the presence of a credible threat from the FDA indicating that they might withdraw approval. In essence, without the pressure of potential consequences from the FDA, companies might delay or avoid performing these essential studies that validate a drug's effectiveness. The public controversy after the Alzheimer's drug Aducanumab received accelerated approval in 2021 was one such example of a failure to conduct confirmatory trials and sparked conversations in Washington about amending the accelerated approval pathway. On December 29, 2022, President Biden signed into law the Consolidated Appropriations Act of 2023, which contained the Food and Drug Omnibus Reform Act (FDORA). The law provided $6.56 billion in total funding to the FDA during the 2023 fiscal year. Part of the funding is dedicated to a series of reforms that improve how drugs become approved through accelerated approval, as well as how their confirmatory trials are monitored.

In addition to funding, FDORA changed the language in the Federal Food, Drug, and Cosmetic Act regarding how pharmaceutical companies can acquire and maintain accelerated approval. FDORA now allows the FDA to require that pharmaceutical companies granted accelerated approval submit progress reports of their post-approval trials every six months. The information in these progress reports must further be accessible to the public on the FDA website. If the confirmatory trials fail to verify the product’s clinical benefit, the FDA now has the power to rely on expedited procedures to withdraw approval. These changes ensure that accelerated approval drugs that are later proven to be ineffective do not continue to be distributed to patients and are recalled as efficiently and quickly as possible. Before FDORA, the provision of accelerated approval drugs was frequently complicated by confirmatory trials that took too long for the efficacy of a drug to be determined. FDORA now allows the FDA to require companies to have confirmatory clinical trials underway before accelerated approval is awarded.

In addition to drug safety, strengthening confirmatory trial requirements will financially benefit the U.S. government, patients, and taxpayers. A 2021 study of Medicare spending in the Journal of the American Medical Association revealed that from 2015 to 2019, Medicare spending on accelerated approval drugs had climbed to $9.1 billion. Half of these funds, however, were spent on treatments where the clinical benefits were unconfirmed. Private insurance companies, Medicare, and Medicaid have consistently paid millions of dollars for drugs with obscure and unverified benefits and risks, leading to raised insurance premiums and wasted tax dollars. Charging vulnerable patients for drugs without evidence that those drugs will improve the patient’s quality of life is not only immoral but also an economic burden on the government and U.S healthcare system. By requiring timely confirmatory trials, the FDA can withdraw drugs that are clearly ineffective and swiftly halt their economic damage, as opposed to letting them percolate into national debt.

Some FDA officials have argued that stronger confirmatory trial enforcement as authorized in FDORA will disincentivize pharmaceutical companies from seeking drug development in areas of unmet medical need. However, as Dr. Gyawali of Queen’s University of Medicine outlines, “an unmet need doesn’t imply that the treatment void should be filled with a drug that provides nothing of value to patients.” In the years ahead, FDORA will play a pivotal role in guaranteeing that confirmatory trials for accelerated approval drugs occur promptly, ensuring both their safety and efficacy. Importantly, it will grant the FDA essential authority to regulate and access crucial clinical trial data, reinforcing the agency's oversight to safeguard public health.