Post by icemandios on Oct 5, 2022 13:56:31 GMT
October 4, 2022 01:12 PM EDT FDA+
User fees in action: FDA unveils new shortened supplement review, rare disease pilots
Zachary Brennan
Senior Editor
Thanks to PDUFA VII, signed into law last Friday by President Joe Biden, the FDA this week unveiled two new industry-friendly pilot programs to advance new rare disease endpoints via additional meetings, and to shorten FDA review times for supplemental apps aimed at unmet medical needs.
The agency this week released eagerly-awaited details behind the shortened pilot, known as the Split Real Time Application Review or STAR pilot program, which will speed up certain FDA reviews of efficacy supplements across all therapeutic areas (thanks to earlier submissions of data), but only for those that propose addressing an unmet medical need.
Similar to FDA’s breakthrough and RMAT designations, and building off of the Oncology Center of Excellence’s expedited Real Time Oncology Review program, which has cut review times in some cases to less than six months, FDA is asking STAR applicants to submit top-line results from adequate and well-controlled investigation(s) that indicate that the drug may demonstrate substantial improvement on a clinically relevant endpoint(s) over available therapies.
Participating drugs must also address an unmet medical need, FDA says, and no aspect of the submission can require a lengthy review time (e.g., REMS), and there can’t be a foreign manufacturing site inspection (FDA says domestic site inspections may be allowed if it does not affect the expedited timeframe).
While each supplemental application (sNDA or sBLA) may vary in terms of review time, the FDA is splitting submissions into two parts, with the PDUFA clock only starting once the agency receives the second part of the submission, which includes final clinical study reports and clinical summaries.
“FDA will communicate the intent for an expedited action in the filing letter,” the agency says. A disqualification from the STAR program due to an incomplete submission also does not preclude a sponsor from re-submitting the supplement.
“To enter the pilot program, applicants who believe their supplement meets the STAR entry criteria may submit a STAR entry request to the relevant review division as either: 1) a stand-alone request, or 2) as part of a Type B pre-sNDA/sBLA meeting request,” FDA adds.
In addition to the STAR pilot, CDER and CBER are working together on the Rare Disease Endpoint Advancement (RDEA) pilot, allowing for additional meetings between the agency and sponsors.
Beginning in Q4 of 2023 (July 1-September 30, 2023), sponsors can submit an RDEA proposal, with FDA selecting one in the first year but expanding in FY 2024 through 2027 to one RDEA proposal per quarter, with a maximum of three per year. For each proposal admitted to the pilot, the FDA says it will conduct an initial meeting and up to three follow-up meetings, while promising to respond to proposals within 60 days following the end of the fiscal year quarter during which the RDEA proposal is submitted.
The FDA makes clear that sponsors seeking to participate should have an active pre-IND or IND for a rare disease, and a proposed endpoint will be considered a novel efficacy endpoint intended to establish substantial evidence of effectiveness for a rare disease treatment, and must have never been used to support a prior approval, unless it has been substantially modified from previous use to support an approval.
The agency says it will give preference to proposals that:
“Have the potential to impact drug development more broadly, such as one that uses a novel approach to develop an efficacy endpoint or an endpoint that could potentially be relevant to other diseases.
Reflect/impact a range of different types of endpoints.
For surrogate endpoints, those that use novel approaches for collecting additional clinical data in the pre-market stage to advance the validation of these endpoints. (If the sponsor is proposing to develop a surrogate endpoint as part of a rare disease application, participation in a prior Type C Surrogate Endpoint meeting is encouraged.)”
Meanwhile, FDA also says it will pilot a regulatory science program that focuses on advancing the development of interchangeable biosimilars and improving the efficiency of biosimilar product development.
In addition to these pilots, the FDA’s Oncology Center of Excellence also recently unveiled its new Project FrontRunner, seeking to encourage sponsors to design trials that support initial approval in earlier cancer treatment settings.
“Initiating the clinical investigation of new therapies earlier in an earlier treatment setting provides more patients the opportunity to receive the investigational agent early enough in the disease course when disease-related factors do not preclude participation in the trial, and when the treatment has the potential to alter the course of the disease more effectively,” the agency explains.
Among the project’s goals is to facilitate engagement with drug sponsors during a drug’s development to support approvals in early clinical setting.
User fees in action: FDA unveils new shortened supplement review, rare disease pilots
Zachary Brennan
Senior Editor
Thanks to PDUFA VII, signed into law last Friday by President Joe Biden, the FDA this week unveiled two new industry-friendly pilot programs to advance new rare disease endpoints via additional meetings, and to shorten FDA review times for supplemental apps aimed at unmet medical needs.
The agency this week released eagerly-awaited details behind the shortened pilot, known as the Split Real Time Application Review or STAR pilot program, which will speed up certain FDA reviews of efficacy supplements across all therapeutic areas (thanks to earlier submissions of data), but only for those that propose addressing an unmet medical need.
Similar to FDA’s breakthrough and RMAT designations, and building off of the Oncology Center of Excellence’s expedited Real Time Oncology Review program, which has cut review times in some cases to less than six months, FDA is asking STAR applicants to submit top-line results from adequate and well-controlled investigation(s) that indicate that the drug may demonstrate substantial improvement on a clinically relevant endpoint(s) over available therapies.
Participating drugs must also address an unmet medical need, FDA says, and no aspect of the submission can require a lengthy review time (e.g., REMS), and there can’t be a foreign manufacturing site inspection (FDA says domestic site inspections may be allowed if it does not affect the expedited timeframe).
While each supplemental application (sNDA or sBLA) may vary in terms of review time, the FDA is splitting submissions into two parts, with the PDUFA clock only starting once the agency receives the second part of the submission, which includes final clinical study reports and clinical summaries.
“FDA will communicate the intent for an expedited action in the filing letter,” the agency says. A disqualification from the STAR program due to an incomplete submission also does not preclude a sponsor from re-submitting the supplement.
“To enter the pilot program, applicants who believe their supplement meets the STAR entry criteria may submit a STAR entry request to the relevant review division as either: 1) a stand-alone request, or 2) as part of a Type B pre-sNDA/sBLA meeting request,” FDA adds.
In addition to the STAR pilot, CDER and CBER are working together on the Rare Disease Endpoint Advancement (RDEA) pilot, allowing for additional meetings between the agency and sponsors.
Beginning in Q4 of 2023 (July 1-September 30, 2023), sponsors can submit an RDEA proposal, with FDA selecting one in the first year but expanding in FY 2024 through 2027 to one RDEA proposal per quarter, with a maximum of three per year. For each proposal admitted to the pilot, the FDA says it will conduct an initial meeting and up to three follow-up meetings, while promising to respond to proposals within 60 days following the end of the fiscal year quarter during which the RDEA proposal is submitted.
The FDA makes clear that sponsors seeking to participate should have an active pre-IND or IND for a rare disease, and a proposed endpoint will be considered a novel efficacy endpoint intended to establish substantial evidence of effectiveness for a rare disease treatment, and must have never been used to support a prior approval, unless it has been substantially modified from previous use to support an approval.
The agency says it will give preference to proposals that:
“Have the potential to impact drug development more broadly, such as one that uses a novel approach to develop an efficacy endpoint or an endpoint that could potentially be relevant to other diseases.
Reflect/impact a range of different types of endpoints.
For surrogate endpoints, those that use novel approaches for collecting additional clinical data in the pre-market stage to advance the validation of these endpoints. (If the sponsor is proposing to develop a surrogate endpoint as part of a rare disease application, participation in a prior Type C Surrogate Endpoint meeting is encouraged.)”
Meanwhile, FDA also says it will pilot a regulatory science program that focuses on advancing the development of interchangeable biosimilars and improving the efficiency of biosimilar product development.
In addition to these pilots, the FDA’s Oncology Center of Excellence also recently unveiled its new Project FrontRunner, seeking to encourage sponsors to design trials that support initial approval in earlier cancer treatment settings.
“Initiating the clinical investigation of new therapies earlier in an earlier treatment setting provides more patients the opportunity to receive the investigational agent early enough in the disease course when disease-related factors do not preclude participation in the trial, and when the treatment has the potential to alter the course of the disease more effectively,” the agency explains.
Among the project’s goals is to facilitate engagement with drug sponsors during a drug’s development to support approvals in early clinical setting.