You might be able to roughly trace where the apples you bought at the grocery store came from – the store has a supplier, who sources from farms, who are responsible for planting and tending to the apple trees. But what about that drug a doctor prescribed you or a friend or family member diagnosed with cancer?
Just like you have a right to know where the food you and those close to you consume comes from, we think you have a right to know how prescription drugs are developed. Here at Novartis Oncology, our approach begins and ends with the patient. Before we begin, we ask ourselves two questions:
Do we understand the underlying mechanism or cause of the disease?
Does this disease represent a significant unmet medical need in patients?
If the answer to both questions is "yes," we develop a research program aimed to better understand the cancer and investigate potential treatments for the patients who need it. We also work with regulatory authorities, including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), to discuss mechanisms that could accelerate drug development such as breakthrough therapy or priority review in the US.
This is where the “life of a potential cancer drug” begins. From early research to when it’s available for a doctor to prescribe, we’ll walk through the entire process.
Target discovery: Scientists at Novartis use what they call the “pathway approach” when trying to figure out the mechanisms of a disease like breast or lung cancer – they examine how proteins form a pathway of interactions in the body, and figure out which one they should target to try and slow or stop the progression of a disease.
Drug discovery: Through computer modeling or other methods, scientists then try and find a chemical compound or biologic that is able to bond with the identified protein and affect its functioning. Often, this is a one-in-a-million chance of finding a match.
Preclinical testing: Once the compound has been identified, our development team gets involved to monitor investigational drug testing in live animals. Often, complex disease mechanisms, as well as safety and pharmacokinetics (i.e. how the drug is absorbed by the body), can often only be understood through the use of animal studies. Novartis keeps this research as limited as possible and always ensures that animal research is scientifically acceptable according to industry requirements and standards.
Clinical Trials: Once the compound is ready for clinical evaluation in humans, an Investigational New Drug application (IND) for the US or Clinical Trial Application (CTA) for the EU is filed so that the investigational treatment can proceed to clinical studies. Clinical trials, which can take years to complete, progress in three phases:
Phase I: A study generally conducted with a small group of patients with the purpose of:
Finding a safe dose of the investigational treatment
Deciding how the investigational treatment should be given
Seeing how the investigational treatment affects the human body and fights cancer
Phase II: A study generally conducted with an intermediate sized (less than 100) group of patients with the purpose of:
Determining if the investigational treatment has an effect on a certain cancer
Seeing how the investigational treatment affects the body and fights cancer
Phase III: A study generally conducted with a large group (100 to several thousand) of patients with the purpose of:
Comparing the investigational treatment with the current standard of care
PoC: Novartis Oncology also conducts “Proof of Concept” trials, which are a mixture of Phase I and II studies. These small-scale studies help give us an early read on a drug’s safety and efficacy to find and advance the most promising drug candidates.
Regulatory Submission: Generally, after Phase I-III studies have been completed, our regulatory team seeks guidance from heath authorities, including the FDA and EMA, on the filing strategy for the investigational treatment. A New Drug Application (NDA) must be submitted in the US and a Marketing Authorization Application (MAA) in the EU – they tell the full story of the investigational treatment. Packaged up in the applications is information about each clinical trial, proposed labeling, safety updates, patient information, directions for use and more.
Approval: A committee associated with/within the FDA or the EMA evaluates the application, and can approve it or require that certain issues be addressed. After approval, the drug is ready to be put on the market for doctors to prescribe. However, the research may not stop there. There are many activities from a regulatory perspective that may be needed, including maintenance of ongoing studies, post-approval commitments, label updates, etc.
Throughout the phases of clinical development and post-market approval, regulatory input is sought and decisions are made based on safety and efficacy evaluations. For each investigational compound, teams work together across many disciplines, including scientists, chemists, disease area specialists, clinicians and more. Novartis Oncology is also a collaborative partner with health authorities around the world, working expeditiously to respond to questions and enable medicines to reach patients as fast as possible.
As you can see, the approval of a drug is truly a team effort – and it can take years of dedication and hard work. Our team is united in our passion for finding new therapies for cancer and that is what motivates us day in and day out.