Reflects Sarepta's Oct 6, 2014 comment on PPMD draft that Safety should be a specific consideration,
This is because Sarepta knows, as shown in their Credit Suisse presentation, that because of the specific charge neutral design of Eteplirsen, it is less likely to have off target effects. The FDA issued change to the PPMD draft guidance puts safety as the 4th general consideration, reduces the discussion of how many ways DMD can be variable and dystrophin measurement needs to be improved, and discusses how accelerated approval may be facilitated.
Some odd bits in this guidance - safety is important, balance of totality of evidence between modest effects and substantial risks can be swayed by patient reported outcomes (PROs)
FDA considers the totality of the available evidence when conducting a benefit-risk assessment.
For example, if the effect size on a sensitive measure of muscle function is modest for a drug
with substantial risks, evidence of the clinical impact of the effect provided by PROs is likely to
be an important basis of benefit-risk assessments (Will drug developers be lining up patients to testify?)
but renal impairment issues can be deferred until after approval if molecular biochemistry suggests lack of impacts, (are they finally recognizing that Eteplirsen has FEWER OFFTARGET IMPACTS)
FDA has long stressed, however , it is appropriate to exercise flexibility in applying the statutory standards for drugs for serious diseases with important unmet needs
-FDA generally will consider the serious and life threatening nature of DMD when. determining the minimum number of patients exposures needed (GOOD)
-Drugs shown to provide an important benefit may need less safety data to provide assurance that risks are commensurate with benefits (GOOD)
-Safety data for a reasonable number of patients exposed to drug for at least one year generally is appropriate to support approval of drugs intended for chronic use in treating DMD (The clock is running now)
FDA had doubts about Sarepta's dystrophin production BECAUSE Prosensa had bad data showing large increases in dystrophin which, under further scrutiny, did not stand up. There were no good baseline data, and the methodology and results were suspect. This poisoned the well for the whole dystrophin-production-skipping therapy for a couple of years, until the Mothers and others said, wait a minute, its working for our kids, why can't more have eteplirsen. Now, with better understanding of the measurement protocols, and acceptance of the efficacy of increasing dystrophin as moderating full DMD toward Beckers, the FDA is striving, correctly, to catch up and speed a treatment for the unmet medical need of DMD. Mendell, Wilton, Muntoni are all on the side of eteplirsen and dystrophin.
FDA is evaluating a first-of-a-kind, first-in-class medical product for human use.
FDA is evaluating a first-in-class antimicrobial for use in food-producing animals.
FDA is evaluating a medical product for a significant new indication.
FDA is evaluating a novel product or use of new technology.
FDA is evaluating a medical product that involves a significant diagnostic,
therapeutic, or preventative advance.
FDA’s assessment of the risk/benefit ratio of a product or class of products is
likely to be controversial or it appears that the risks and benefits are of similar
magnitude, especially where the products may have a narrow therapeutic effect.
FDA has significant safety concerns about a class of products. This scenario includes such concerns in pre- or post-market situations (e.g., significant safety concerns relating to the pre-market re
view of a medical product regulated by FDA, or significant safety concerns relating to the post-market review of such a medical product, including significant concern
FDA has significant questions or concerns about a study, including a clinical trial......
FDA personnel have a significant difference of opinion on a complex matter
FDA is seeking outside expertise on scientific techniques or research
From Draft Guidance for the Public and FDA Staff on Convening Advisory Committee Meetings, August 2008
A. Considering when to Convene a Meeting
In most instances, FDA has discretion to consid
er whether to refer a matter to an advisory
committee for consideration.
In those instances in which FDA is not legally compelled to refer a matter to an advisory
committee, it may nevertheless choose to do so voluntarily. When considering whether
to convene such a meeting, FDA should consider the following three factors:
(a)Is the matter at issue of such significant public interest that
it would be highly beneficial to obtain the advice of an advisory committee as part of the
agency’s regulatory decision-making process?
(b)Is the matter at issue so controversial that it would be highly beneficial to
obtain the advice of an advi sory committee as part of the agency’s regulatory
(c)Is there a special type of expertise that an advisory committee could provide
that is needed for the agency to fully consider a matter?
Its on the site for comments on gov regulations dot gov in the docket for fda dystrophin workshop,.
Information for Healthcare Professionals (Drugs)
Resources for You
Information for Healthcare Professionals (Drugs)
FDA Drug Info Rounds Video
Know Your Source: Protecting Patients from Unsafe Drugs
Global Alliance of Drug Information Specialists (GADIS)
Drug Safety Information
Transcript: Accelerated Approval Program video
Captain Mary Kremzner: Now Cat, exactly how does the FDA determine when an expedited approval is warranted?
Commander Catherine Chew: Generally drugs are approved under Accelerated Approval if they have the potential to impact factors, things like survival, day‑to‑day function or the likelihood of stopping a disease from progressing and becoming an even more serious condition.
Captain Mary Kremzner: Now Cat earlier you mentioned filling an unmet medical need. How would you define that?
Commander Catherine Chew: An unmet medical need simply means providing a therapy when none exists or providing a new therapy that may be superior to or less toxic than an existing one.
Captain Mary Kremzner: So without the standard clinical outcomes how does FDA determine if a treatment is potentially effective?
Commander Catherine Chew: Great question Mary. Accelerated Approvals use what we call a surrogate end point in clinical trials. These are markers or a physical sign of sorts used as an indirect measurement to predict a clinically meaningful outcome like survival or symptom improvement.
Captain Mary Kremzner: So exactly how does the surrogate end point save time in the drug approval process?
Commander Catherine Chew: Well for example, instead of having to wait to learn if a drug prolonged survival in cancer patients the FDA has approved drugs based on evidence that they shrink tumors. As a surrogate end point, tumor shrinkage is reasonably linked to real clinical benefit.
Captain Mary Kremzner: Okay, so let me make sure I have this. Let’s say a drug goes through Accelerated Approval and gets to market, how do we know if it really provides that clinical benefit?
Commander Catherine Chew: Any approvals given based on surrogate end points are on the condition that the sponsor will conduct post-marketing clinical trials to verify the anticipated benefit. If these trials, called Phase 4 Confirmatory Trials, shows the drug does in fact provide a clinical benefit then and only then does the FDA grant traditional approval for that drug.
Somebody needs a good DNA vaccine for pandemic influenze-US Gov just awarded GSK $200 million plus
Contract No. HHSO100201500010C was awarded on May 22, 2015 to GlaxoSmithKline LLC in the amount of $79,998,267 for the base period and either a $120,000,000 or $112,000,344 option period to support the development of cell-based influenza virus vaccines against influenza subtypes with pandemic potential.
Contracting Office Address:
Office of the Assistant Secretary for Preparedness & Response (ASPR)
Department of Health and Human Services
330 Independence Ave. SW
You don't need much of a sales force when all the neurology centers across the country are participating in DMD trials and all the Duchenne charities make patient and therapy information available on their blogs. If FDA approves it, the boys will get it.
J&A Statutory Authority:
FAR 6.302-1 - Only one responsible source (except brand name)
Contract Award Date:
September 30, 2015
Contract Award Number:
Added: May 22, 2015 4:11 pm
Notification of a Justification and Approval in accordance FAR 6.302-1 to procure the antiviral drug, brincidofovir, from Chimerix, Inc. for the treatment of smallpox.
The documentary was successfully funded, just made it over the finish line, so coming out
later this year, probably Sep-Oct (about the same time as the AdComm???)
About the DMD mothers and their campaign to get FDA approval for a drug for their boys. If you made
money, as I did, contribute to finish this documentary, 4 days left.
May 8 PT 36
CREDIT SUISSE SECURITIES RESEARCH & ANALYTICS
(SRPT)SMALL & MID CAP RESEARCH
Q1 Earnings: FDA Meeting for Eteplirsen Around the Corner
SRPT expects to have a meeting with the FDA in Q2 to review the available
eteplirsen data and hopefully receive a green-light to file the NDA shortly thereafter.
SRPT recently completed the fourth biopsy in eleven out of
twelve patients.We are encouraged by the
progress withthe ongoing studies, including the on-track
enrollment of the confirmatory study.
Fourth round of biopsies
completed:SRPT has collected
11/12 biopsies and intends to run the necessary analyses
using new protocols developed in
conjunction with the FDA, including Western blot,
RT-PCR, and immunohistochemistry assays
As indicated, major news had to be publicly released. That 4:03 Press Release was the Regulation FD path for news, now the Sarepta CEO can tell us a lot more at PPMD conference about patient quality of life, follow on exon trials 53, 44 , methods of dystrophin measurement confirmation by multiple methods.
cannot release material information (which would cause person. tobuy or sell stock) without releasing generally under SEC regn FD. So if there is new news, has to be released before or after PPMD panels. but can review public data like status of various clinical trials apart from results.