WHITE PAPER

Indication Expansion

Maximizing Potential and Efficiencies: Regulatory and Practical Considerations for Investigational New Drug Applications

Author

Dawn Chitty, MSSenior Director, Regulatory Strategy & Agency Liaison PRA Health Sciences

Receiving a “May Proceed” letter from the US Food and

Drug Administration (FDA) is a cause for celebration. As the

company looks forward to the studies ahead, the regulatory

affairs team will plan for the required or expected changes

while building time to address unexpected amendments

as they arise. Fast forward 12 months and you will find the

regulatory team managing multiple INDs for the same product,

but all with different timelines and requirements.

Given the cost and time needed to develop new products,

understanding potential uses across indications is critical to

increasing a product’s value in the expensive, time-consuming

world of drug development. If a molecule shows solid

potential for a new indication, researchers can often bypass

preliminary safety studies, shaving years off of the safety

and efficacy research needed to satisfy FDA requirements.

Researchers can also gain insight into the ways patients are

likely to respond to various dose levels and further understand

the biomarkers that will help to identify the most likely

responders, further streamlining future studies. Additional

efficiencies can be realized by ensuring development projects

using the same drug are not treated like separate drugs.

Consolidating General Information Into One PlaceCrossreferencing previously filed INDs is common for Modules

3 (Quality) and 4 (Non-clinical Study Reports). This ability to

crossreference presents an opportunity to centralize most

information in these modules of 1 IND, typically the first IND

filed and often referred to as the “parent” IND. In instances

where the same formulation is used for multiple indications,

there is an opportunity to centralize most information in

Module 3 of 1 IND. Managing data that come from advancing

the manufacturing process for a product becomes less

daunting when all available data, from scale up work to

ongoing stability evaluations, are submitted only once. At

times, pre-clinical summaries and tabulations in Module

2 (2.4 and 2.6) focus only on studies relevant to a specific

indication. If written in a general manner to cover all available

data and indications, minimal updates will be required as new

information becomes available. Taking this approach lends

itself to easy referencing of information and also allows new

data to be submitted once rather than sequentially submitting

the same information into multiple INDs.

Aligning Dates to Streamline ReportingAligning dates across INDs can lead to several efficiencies.

For example, if all INDs have the same date for annual reports,

the Development Safety Update Reports (DSURs) can be

syncronized. It is often recommended to move all studies into a

consolidated DSUR to ensure a complete and comprehensive

review of all study data rather than reviewing a study-specific

DSUR for each indication. As the project progresses, this also

allows for easier and faster integration of data for integrated

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Executive SummaryWhether you are a large pharma or small biotech company, there are many potential benefits and challenges when developing a

single product candidate that provides clinical benefit across multiple indications. A single mechanism of action (MoA) applicable to

different indications and patient populations means more conditions can be treated quicker and can result in more efficient research

and development (R&D) for clients. Challenges include the growing need to pursue indication-specific pricing and to develop

a strategy that optimizes expected patent term extensions. Taking time to strategically plan for Investigational New Drug (IND)

management can maximize limited resources, simplify activities surrounding IND maintenance, and ensure IND holders comply with

required responsibilities.

safety and efficacy summaries needed upon New Drug

Application (NDA) or Biologics License Application (BLA)

submission. Most programs will use multiple CROs during

product development but that does not necessitate separate

DSURs from each CRO. With some planning and forethought,

DSUR writing can be centralized with one CRO even though

multiple CROs may conduct the studies. There are a variety of

mechanisms that promote data sharing and consolidation, from

integrating databases to sharing data in an agreed upon format

that allows the data to be migrated into a centralized database.

Furthermore, aligning the safety data evaluation will set the

review schedule for the Investigator’s Brochure (IB). Most

companies conduct (and many regulators expect) an annual

IB review. Having the consolidated data and conclusions

from a centralized DSUR makes this activity more efficient

by eliminating redundant safety data reviews that would

otherwise be available in a rolling format.

Pediatric ConsiderationsPediatric studies are required for new drugs and biologics by

the Pediatric Research Equity Act (PREA) with few exceptions,

mostly for orphan drugs. With the recent implementation

of the RACE Act and renewed focus on pediatric patients,

the oncology field has fewer opportunities for waivers.

The Pediatric Study Plan should be planned early in the

development timeline. Because additional indications may

amount to additional pediatric requirements, the targeted

pediatric population for the new indication should also be

considered early in the development process. The ability

to plan and execute one pediatric pharmacokinetic study

that covers the entire potential dose range expected across

multiple indications is much more desirable and, in most cases,

more cost-effective than executing multiple, similar studies.

Think About Labeling Sooner Rather than LaterEarly in a development program, a Target Product Profile (TPP)

should be developed to ensure the commercial goals (eg,

targeted indications and patient populations) are identified

and the development program is designed to support these

goals. There are two possible labeling scenarios when one

drug is being developed for multiple indications:

1. Similar indications will likely have similar class labeling

(eg, multiple oncology indications)

2. Different indications may have multiple sets of class

labeling required (eg, Rheumatoid Arthritis/Crohn’s

disease, Parkinson’s disease/restless leg syndrome)

Companies may need to consider differences among the

indications as they develop the label. If there are class labeling

requirements that cannot be accepted from a marketing

standpoint, now is the time to plan a strategy that allows for

development activities that may support modified or deleted

class labeling requirements.

Opportunities for Accelerating Development and Eventual ApprovalOpportunities for basket/master protocols should be

evaluated when appropriate. Basket/master protocols are

becoming more prevalent and allow multiple indications to be

evaluated, facilitating faster development timelines. Oncology

and anti-inflammatory drugs, for example, commonly use

basket/master protocols as the same MoA may impact multiple

similar conditions. Early engagement with the FDA and other

health authorities is critical to determine whether a basket/

master protocol is appropriate.

There are also many regulatory tools and designation

programs available to accelerate the review of NDAs/BLAs

or that provide other financial incentives. Depending on

White Paper | Indication Expansion

the indications being pursued, the impact and timing of

participation in these programs may dictate priorities in

development. Expedited reviews will result in faster time to

market and the impact on the patent landscape should be

carefully reviewed. Obtaining orphan designation has many

benefits but can also cause downstream development issues

if pursued too early and/or without sufficient support.

ConclusionManaging multiple projects is complex. PRA understands

the essential role regulatory affairs plays in helping expedite

time to market and in positioning a product for commercial

success. A clear regulatory strategy is invaluable to navigate

the many challenges of drug development, registration,

and commercialization. Proactive steps such as those

discussed above, as well as others, can simplify the complex

development journey.

While the specific items discussed are US-focused, a

comprehensive global development or expansion strategy

can provide similar opportunities across multiple markets.

PRA has the depth of experience and knowledge to

determine the optimal path forward for each client. We

serve as a consultative, full-service, or a hybrid partner to

our clients, depending on their needs. Our team has the

regulatory and drug development expertise to help clients

determine the best approach to maximize IND efficiencies.

White Paper | Indication ExpansionSEP 2020

PRA Health Sciences conducts comprehensive Phase I-IV biopharmaceutical drug development. To learn more about our solutions, please visit us at prahs.com or email us at prahealthsciences@prahs.com.

Contact Information

For further information, or to discuss any aspect of PRA’s services offered in the field of indication expansion, please contact your PRA account director or one of the employees listed below:

Dawn Chitty, MS

Senior Director, Regulatory Strategy & Agency Liaison

ChittyDawn@prahs.com

World Headquarters

4130 ParkLake Avenue, Suite 400

Raleigh, North Carolina 27612 USA

Phone: +1 (919) 786 8200

Fax: +1 (919) 786 8201

www.prahs.com

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T 2020White Paper | Indication Expansion