Application Guidance

The TREAT-NMD Advisory Committee for Therapeutics (TACT) is a multi-disciplinary group of experts with broad experience in all phases of drug discovery (target identification and early non-clinical studies) and development (non-clinical toxicology studies and clinical trials) including registration (regulatory approval for the drug).

The committee’s Core group consists of 11 members who meet twice each year to review up to 4 applications on each occasion. These applications are reviewed by members of the core committee, as well as representatives from an additional pool of more than 80 expert key opinion leaders, including patient representatives, who have a wide-range of expertise from disciplines needed to address specific issues related to the therapeutic under discussion.

Based on questions received by TACT so far, it is important to note that participation in a TACT review is NOT an endorsement by TACT or by TREAT-NMD, that a drug has any particular status in terms of regulatory or funding potential. The review is purely advisory and educational in its focus and does not assign any grading of the “quality” of the drug or planned programme. TACT is not a funding organization but provides evaluation and recommendations which might facilitate development of a review into an application to a funding organization.

Materials submitted to TACT should include (but may not be limited to) the items below which are also listed on the TACT application form.

• Hypothesis: what is the biological support for the drug to be considered as a therapy for NMD?
• Non-clinical data: are available data both consistent with currently accepted best practice standards for DMD and SMA, and do they provide acceptable evidence that the drug might be considered for clinical studies? Have non-clinical data been reproduced in more than one laboratory? Are the non-clinical studies supportive of the route and dosage of administration required for a clinical trial?
• Drug substance: what is it? Is it available? Could it be commercialized?
• Pharmacology: drug potency, selectivity, proof of concept, advantages over competitive approaches.
• Pharmacokinetics (time course upon administration) and pharmacodynamics (intensity of effect).
• Formulation and administration: especially the relationship between dosing in the non-clinical studies and subsequent clinical trials. Is there appropriate justification for the scaling up of dosing? Is the route of administration compatible with clinical trials?
• Evidence of safety: where the target population is paediatric, what previous paediatric regimes have been used? If there is a perspective for long term use, do previous studies reflect this or would further studies be needed to extrapolate to different populations or duration of dosage?
• Plans for clinical trials: have the applicants considered all relevant aspects of trial design for the disease under consideration? Would patients be available and recruitable based on actual estimates at intended sites and data available from established international patient registries? Are outcome measures well understood and have they been used in previous studies? How would a trial for this drug fit with ongoing or planned studies in the disease under consideration?
• Do the patient representatives agree that a trial with this drug would be an acceptable burden on the target population? Have the researchers fully addressed the risk/benefit balance for these plans? If marketed would the drug make a clinically meaningful contribution to the existing standards of care for the condition? e.g. DMD or SMA.
• Any regulatory advantages or issues: do the applicants understand the process for seeking advice (such as orphan drug products) and registration? e.g. FDA and EMA.  Are there regulatory issues in countries considered, relevant to this drug?
• Intellectual property protection.

It is understood that not every project will be fully developed in all of these areas.  However, this list of considerations is critical in order to understand and minimize controllable risk and to advise on the appropriate strategic direction, therefore allowing a meaningful set of recommendations from TACT.

As detailed in the terms of reference, following review of a therapy by TACT, an evaluation and recommendation report will be sent to the applicant no later than six weeks after the review meeting has taken place.

The TREAT-NMD website provides information about applications which have been reviewed at a TACT meeting, including the timing of the review.  Therefore any parties interested in an applicant’s report, such as funders, are encouraged to request the TACT report from the researchers directly. TACT will never issue a report to anyone but the applicant.

All TACT reports given to the applicant are provided in PDF format on TACT letterhead. It is expected that applicants who choose to share their TACT report with other interested parties will circulate the original TACT report, unmodified and in its entirety. TACT reports should not be revised or altered when provided to third parties, as they will no longer accurately reflect the committee’s discussions and recommendations.

The TACT process for any given review is not iterative and does not include ongoing feedback to the development programme. However, the committee would consider reviewing a programme at a later time if it has substantially progressed or changed and if the committee felt that it could add further value.

General References:

1. FDA website
   Whom to contact about Orphan Product Development
2. EMA website
   Orphan drug information
   Data on medicines (ISO IDMP standards)
3. e Agencies (HMA) website – Clinical Trial Facilitation Group (CTFG)
4. NIHR clinical trials toolkit
5. EUDRACT website
6. European commission website – Eudralex Volume 10 clinical trial guideline
7. NINDS Grants PAR for Translational R21 Program
8. NINDS Grants PAR for U01, U24 and U54 Program