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 preclinical studies) and development (preclinical toxicology studies and clinical trials) including registration (the Regulatory approval for the drug).

The Committee’s Core group consists of 9 members who meet bi-yearly. Proposal reviews and meetings include representatives from an additional pool of more than 80 experts, including patient representatives, who have a wide-range of expertise from disciplines needed to address specific issues related to the drug under discussion. TACT reviews drugs presented as having a clear perspective within the translational process with the long-term goal of an intended clinical trial and potential registration. Candidate drugs may be targeted to any form of inherited NMD.

Based on questions received by TACT so far, it is important to note that the conduct of a TACT review is NOT an endorsement by TACT or by TREAT-NMD that a drug has any particular status from a 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?
  • Preclinical 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 preclinical data been reproduced in more than one laboratory? Are the preclinical 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 preclinical 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 on all of these fronts.  However, this list of considerations is critical in order to understand and minimize controllable risk and/or to advise on the appropriate strategic direction, and therefore allow a meaningful set of recommendations from TACT.

As detailed in the terms of reference following review of a drug by TACT, an evaluation and recommendations report is made available to the investigator/researcher who requested a TACT review within six weeks.

The TREAT-NMD website provides information about the projects reviewed and planned to be reviewed at TACT meetings and the timing of TACT’s recommendations report.  Therefore any parties interested in the report, such as funders, are encouraged to request the TACT report from the researchers directly.

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. EMEA website
    National European Agencies (responsible for IMPD evaluation)
    Orphan drug information
  3. Head of Medicine Agencies (HMA) website - Clinical Trial Facilitation Group (CTFG)
  4. MRC roadmap for clinical trials
  5. Drug development pathway
  6. EUDRACT website
  7. European commission website - Eudralex Volume 10 clinical trial guideline
  8. NINDS Grants PAR for Translational R21 Program
  9. NINDS Grants PAR for U01, U24 and U54 Program
  10. Information for sponsors on preparing an IND (USA) orIMPD (EU)
  11. Production assistance for cellular therapies website
  12. TACT glossary
 
12 Apr 2017