The below article is Part Three of a series that began in the Winter 2015/2016 edition of the FARA Advocate.

"Drug Development Series: Drug Approvals and What Happens Next"

By Jane Larkindale, PhD

Once a drug has completed a successful Phase III trial, unfortunately the drug is not automatically on the shelves of the local drug store the next day. There are still several steps that need to be worked through before a doctor can prescribe the drug to patients.

First, the drug sponsor has to pull together all the data that they have and submit it to the FDA (or equivalent authorities outside of the US) and ask for approval of the drug. This is through a request for a “New Drug Application” (NDA) for a drug or a “Biologics License Application” (BLA) for a biological therapy (e.g. gene or protein therapy). These applications are typically about 100,000 pages long and contain all of the information about the drug from preclinical data, through the data from all of the clinical trials and also information about the process for making the drug, delivering the drug, quality control etc. It also includes information on what will be on the drug’s label - which is critical as it will determine who the drug will be approved for (e.g. all FA patients or perhaps a subset of FA patients like ones who show signs of cardiomyopathy, or those who are still ambulatory, depending on what population of patients the drug has been tested in). A company will often meet with the FDA several times while developing the NDA to make sure that it includes all of the information that the FDA needs in the application. Putting this together takes some time – for example, Santhera completed a successful Phase III study for idebenone in Duchenne Muscular Dystrophy in mid 2014. In June of this year they announced that they are in discussions with the FDA about an NDA, but the NDA has yet to be filed. 

Once the NDA or BLA has been filed, the FDA has 60 days to complete a preliminary review to determine if they think there is enough information to continue into a full review phase. This seems slow, but they are reviewing 100,000 pages of information on something they may know little about! If they refuse the application, they will explain to the company why, and it may re-apply. Assuming the application is accepted, the FDA then has 10 months to review the information for most drugs, but 6 months in the case of priority review (a new FA drug would likely have priority review due to FA being an orphan drug for a disease with a high medical need). So, if Santhera’s DMD application was submitted today, an NDA would not be approved until November of 2016.

Once the NDA is approved, technically the company can start selling the drug immediately. However, the FDA will require additional studies – it requires surveillance of all new drugs for safety issues over time. In cases where drugs are approved on smaller trials, as would be the case in FA, they may request formal “Phase IV” studies where there is more formal investigation of side effects over a longer time, and/or in additional populations of patents that were not studied in the original trials (e.g. older patients, patients with more advanced or less advanced disease).

Even once a drug is legally able to be marketed, the company still has work to do. It needs to figure out how to get the drug to the patients – this may be easy if it is a pill that can be stored anywhere, or very complicated if the new treatment requires complex medical procedures to implement (e.g. something that needs to be infused into the brain). So, it needs to develop a supply chain to make sure that the drug can be delivered to patients. It also needs to negotiate with insurance plans (including Medicare and Medicaid) to ensure that the drug is covered by insurance, or it will likely be too expensive for most patients.

Finally, once it has figured all of this out, it needs to educate the clinicians that are treating patients about the new drug – who should be using it, at what doses, what side effects to look for etc. Not every doctor and every patient will instantly know about a new drug – which is why patients can help by following what is going on in the drug development world, so they can ask their clinicians about new developments, and whether that drug would be appropriate for them. Clinicians who treat a lot of FA patients, such as those in the Cooperative Clinical Research Network for FA are likely to be among the first to understand the details of a new drug, as they will likely have been involved in the trials, but patients being seen in smaller clinics may need to bring a new drug to their doctor’s attention. FARA will be providing information as needed when we get to this stage.

Stay tuned for next month's installment of the Drug Development Series.

← Read Part Two: "Accelerating Drug Development and Clinical Trials"