CLINICAL TRIALS

As evidenced by the COVID-19 pandemic, it is essential to bring new life-saving vaccines and antivirals to the market quickly. To support pharma and biotech companies in developing drugs and vaccines for serious diseases and unmet medical needs, the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have set up different expedited review programs.

Human Challenge Trials (HCT) or Controlled Human Infection Models (CHIM) are trials in which healthy volunteers are administered a pathogenic or virulent strain of a challenge agent - which can be a virus, bacteria, or parasite - together with a vaccine or antiviral.

In current drug development, Human Challenge Trials can be used in a variety of ways, like dose-finding studies, in preparation for field trials, but the most common use is that HCTs are used as phase 2 proof-of-concept (PoC) trials.

These Human Challenge proof-of-concept trials are designed to provide early evidence about efficacy and determine if a drug is likely to be successful in later clinical trial phases. Hence, PoC studies can guide drug developers to make smarter “go or no-go” decisions about whether to proceed with larger, more expensive studies in the next stage of drug development. The results of PoC studies are pivotal for strategic decisions in early drug clinical trial development.

The main advantage of Human Challenge Trials compared to ‘classic’ field trials is two-fold. On one side, they require fewer subjects compared to field studies (approx. 40-60 vs 120-240) and they can be completed in a shorter timeframe (approx. 3-4 months vs 12-16 months) compared to field trials. Challenge trials for respiratory diseases are also not seasonally dependent, therefore giving an additional advantage that they can be performed any time of the year. This also allows obtaining proof of concept data in years with a ‘low circulation’ season.

Expedited review programs in the US

The FDA has several programs to support the expedited development of new drugs and vaccines for the treatment and prevention of a potentially life-threatening condition and unmet medical needs.

Fast Track Designation

Fast Track was introduced in 1992 by the FDA to support the development of drugs for serious conditions. To be eligible for Fast Track designation, the drug should be developed to treat a serious condition or must demonstrate the potential to address unmet medical needs.

To be successful with a request for Fast Track designation in a condition where there are already available therapies, the new treatment should fulfil at least one of the following criteria:

• Show superior efficacy or improvement compared to the existing therapy

• Improved safety profile compared to existing therapy

• Provide an alternative to patients that are not eligible for the existing therapy

• Improve patient compliance, in such a way it is expected to lead to a better outcome

• Address an emerging or anticipated public health need

Fast Track designation can be obtained based on non-clinical efficacy data and can be submitted at the time of IND submission or later, but ideally as early as data are available that indicate the drug’s potential to address an unmet medical need.

Obtaining a Fast Track designation offers multiple advantages to pharma companies:

• More frequent meetings and interactions with FDA to discuss the drug’s development plan

• Eligibility for Rolling Review (if relevant criteria are met)

• Eligibility for Accelerated Approval and Priority Review (if relevant criteria are met)

Breakthrough designation

Breakthrough Therapy designation was introduced under the FDA Safety and Innovation Act in 2012.

To be eligible for a Breakthrough Therapy designation, the drug should be intended to treat a serious condition. Preliminary clinical evidence should demonstrate the new drug showing a substantial and clinically meaningful effect on an important outcome over a placebo (or a well-documented historical control where applicable).

When there is already a therapy available, the clinical evidence should indicate that the drug may demonstrate a substantial improvement on a clinically significant endpoint(s) over available therapies.

Breakthrough Therapy products are entitled to the below advantages:

All Fast Track designation program features:

• Intensive guidance on an efficient drug development program, beginning as early as Phase 1

• Organisational commitment involving senior managers and experienced review staff, as appropriate, in a collaborative, cross-disciplinary review

• Eligibility for Rolling Review and Priority Review if relevant criteria are met