Bringing Oncology Drugs to Market

In the United States the Food and Drug Administration (FDA) is responsible for reviewing data for a new oncology drug to assure the safety and effectiveness prior to market release of the medicine. A sponsor (usually the drug company) is responsible for testing the oncology drug and submitting data (evidence) proving the oncology drug’s safety and effectiveness.  Other governments around the world have similar review processes.  Drugs in other branches of medicine have similar processes; an estimated 40 percent of the pharmaceutical industry’s spending on development is on oncology drugs.

Clinical Trial Sponsors

Sponsors are typically pharmaceutical companies, foundations, research institutions, and governmental agencies such as the National Institutes of Health (NIH). They initiate the study by submitting documentation to FDA, clinical investigative organizations, and Institutional Review Boards (IRB) for review and approval. They do not have contact with the patients/subjects, but rather are responsible for monitoring the activities of the clinical investigator to assure compliance to the investigational plan. Clinical investigators administer the test article (investigational drug) to the subjects, complete case report forms, and record and report adverse events.

Biotech researchA sponsor can also be a physician who acts as a sponsor-investigator initiating and conducting the study. The physician is responsible for submitting documentation to FDA and/or an IRB and performing the study including administering the test drug to the subjects; completing case report forms; and recording and reporting adverse events.

Sponsors of new oncology drugs, in addition to needing to prove safety and effectiveness, also need to make a risk/benefit assessment of the oncology drug. The assessment of risk is specific to the type of cancer, the patient population, and the cancer progression/stage. The assessment of benefits looks at the total number of patients in a population and the number who might benefit and the amount of benefit from the oncology drug. An oncology drug may be developed to improve survival rate or to lengthen survival time. At any point during the development process, an oncology clinical trial may be stopped if the safety and/or the effectiveness of the new oncology drug become unacceptable.  Sometimes the trial is stopped if the benefit(s) are so great the sponsor and regulatory authority thinks all patients in the trials should get it.

Oncology drugs are typically given to patients as a “cocktail,” meaning more than one drug is used at a time. This mixing of multiple drugs makes oncology trials more complicated than other drug trials. Historical data from other oncology drug trials may be used to compare the new oncology drug to the FDA-approved oncology drug; however, this type of comparison requires that the new oncology drug trials recruit more subjects to prove tight confidence intervals for the new oncology drug. In other words, the laws of statistics demand more patients in the trial for the new drug or drug combination in order to show effectiveness.  Additionally, disease progression in oncology patients can affect the outcome of the clinical trial without necessarily being a safety or effectiveness concern of the new oncology drug.

More on the clinical trial process for new cancer drugs.

Other countries have their own regulatory agencies, but a drug that is approved elsewhere cannot be sold in the United States until the FDA approves it.  Drug manufacturers still can benefit from getting their products approved in other countries as it helps garner FDA approval.  The criteria for approval are often similar, and clinical trial data used for one regulatory agency can be submitted to other agencies.  Further, if a drug achieves clinical use in another country, real data from real patients can be obtained in greater quantities.  The U.S. and other countries have teamed up to form the International Conference on Harmonization (ICH) to coordinate approval criteria with the goal of making drug approval less expensive and faster.

The FDA has a fast-track program for drugs that hold promise for filling holes in the existing panoply of medicine and for life-threatening diseases.  Drug makers can also request a special “accelerated approval” for their new products in which the criteria for determining effectiveness are different from those in the normal process.  A 2018 article in undark reported that 66 of 404 new drugs approved from the FDA between 2004 and 2018 were approved under the auspices of the Accelerated Approval Program.  The number increased in the later part of that period.

Label expansion

Chemotherapy drugs are often prescribed off-label; once the regulators have approved a new medicine for one indication it can be used for diseases.  Nevertheless, sometimes the FDA will change the approval to cover additional cancers not named in the initial release.  Anti-cancer drugs are usually tested in adults before expansion to pediatric patients; this is a conscious strategy by the drug developer driven by both estimates of ease of approval and worries about liabilities.

Orphan drugs

Drugs intended to treat rare diseases affecting less than 200,000 US residents can be designated “orphan drugs”. The name orphan was given because of the concern that drug companies would fail to develop medicines without the promise of a big market.  Congress passed the Orphan Drug Act, which allows the government to give sponsors incentives to develop new drugs for the treatment of rare conditions, including several different types of cancer.  However, use of orphan drugs has been growing at a faster rate than broader pharmaceutical market, and in 2021 over half the new drugs approved by the FDA fell in the orphan category.

Making new drugs available to patients

Investigational drugs which have not yet been approved but which scientists are looking into can be given to human patients under the auspices of clinical trials.  There are many restrictions and controls on these trials and only some patients are eligible.  Other FDA approved ways patients may receive investigational drugs include

Compassionate exemption – The FDA reviews special requests submitted by the patient’s doctor and the drug sponsor.  This is usually done only when the patient does not meet the criteria for a clinical trial.  Through its Investigational New Drug program the FDA accepts requests from pharmaceutical companies who want permission to give a drug to a patient that does not meet clinical trial criteria when there are no other reasonable treatments available.  Cases are evaluated patient by patient.

While the Investigational New Drug program encompasses medicines for all diseases, investigational cancer drugs covered under this program are typically also called Group C drugs. Group C is a designation of the US National Cancer Institute and is not used outside the US.  This program was created because the medical community recognized the long delay between when scientists recognize a compound fights cancer and when it is approved by the FDA.  The drugs are typically in phase III clinical trials and the patient who gets the Group C drugs has to go through the same informed consent process that trial participants do.