SRPT
Ayer andaba liada y no metí las razones para el corto. En primer lugar que la aprobación acelerada lleva una serie de obligaciones en forma de ensayos: era obvio que necesitaban pasta; en segundo, el técnico daba entrada.
Necesitan lo siguiente:
to verify the clinical benefit of eteplirsen, conduct a 2-year randomized,
double-blind, controlled trial of eteplirsen in patients who have a confirmed
mutation of the DMD gene that is amenable to exon 51 skipping. Patients should
be randomized to the approved dosage of eteplirsen (30 mg/kg weekly) or to a
dosage that provides significantly higher exposure, e.g., 30 mg/kg daily.
The primary endpoint will be the North Star Ambulatory Assessment.
Draft Protocol Submission: 10/2016
Final Protocol Submission: 04/2017
Trial Completion: 11/2020
Final Report Submission: 05/2021
Therefore, based on appropriate scientific data, FDA has determined that you are required
to conduct the following:
3095-2 A two-year carcinogenicity study of intravenously administered eteplirsen in rat.
The timetable you submitted on September 16, 2016, states that you will conduct this study according to the following schedule:
Draft Protocol Submission: 12/2016
Final Protocol Submission: 03/2017
Study Completion: 04/2020
Final Report Submission: 06/2020
Reference ID: 3987286
3095-3
A 26-week carcinogenicity study of eteplirsen, administered by a clinically
relevant route, in an appropriate transgenic mouse model.
The timetable you submitted on September 16, 2016, states that you will conduct
this study according to the following schedule:
Draft Protocol Submission: 10/2016
Final Protocol Submission: 01/2017
Study Completion: 05/2018
Final Report Submission: 06/2018
A study to evaluate:
1.patient immune responses, including IgM and IgG isotypes, to eteplirsen, its induced dystrophin protein, and full length dystrophin;
2.the impact of immune responses on product PK and clinical efficacy and safety.
The assays for antibodies to eteplirsen, the induced dystrophin, and full length dystrophin should be performed with sampling times optimized to detect early, peak, and late antibody responses, and should be fully validated.
3.for subjects whose serum screens positive for antibodies, the samples
should be tested for neutralizing activity, to product activity, and/or
product uptake. Antibody titer and persistence should be monitored
throughout the duration of the study.
4.in patients who seroconvert, antibody levels should be monitored until
they return to baseline.
5.for patients developing hypersensitivity responses, assays to evaluate
IgE responses including skin testing or RAST assays should be
developed and employed.
Until these assays have been fully validated and reviewed by FDA, sufficient
samples should be banked and stored under appropriate conditions so as to allow for re-testing if deemed necessary.
The timetable you submitted on September 16, 2016, states that you will conduct this study according to the following schedule:
Draft Protocol Submission: 01/2017
Final Protocol Submission: 08/2017
Study Completion: 12/2017
Final Report Submission: 02/2018
We remind you of your postmarketing commitments:
3095-5
Conduct a 2-year controlled trial in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 or 53 skipping with a phosphorodiamidate morpholino oligomer (PMO) designed to bind to a regulatory site governing splicing of the corresponding exon. The trial should include at least two well-separated doses of each PMO, with the high dose designed to provide the greatest dystrophin response possible, based upon preliminary dose-finding, with an expectation of acceptable tolerability. The primary objective of this study will be to evaluate the effect of the two PMO doses (combined-active group) compared to control on the North Star Ambulatory Assessment.
The secondary objective will be to evaluate dystrophin levels as percent of normal by Western blot, with tissue to be obtained by needle biopsy.
The timetable you submitted on September 16, 2016, states that you will conduct this study according to the following schedule...
http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2016/206488Orig1s000ltr.pdf
Informe completo FDA:
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PeripheralandCentralNervousSystemDrugsAdvisoryCommittee/UCM481911.pdf
«Después de nada, o después de todo/ supe que todo no era más que nada.»
