Someone is posting falsehood that no Eteplirsen treatment in Europe. the exon 53 skip is ongoing in Europe.
posting materially false information knowingly creates legal liability
4053-101: PHASE I/II STUDY
Official Title: A 2-Part, Randomized, Double-Blind, Placebo-Controlled, Dose-Titration, Safety, Tolerability, and Pharmacokinetics Study (Part 1) Followed by an Open-Label Efficacy and Safety Evaluation (Part 2) of SRP-4053 in Patients With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping
Purpose: This is a first-in-human, multiple-dose 2-part study to assess the safety, tolerability, efficacy, and pharmacokinetics of SRP-4053 in Duchenne muscular dystrophy (DMD) patients with deletions amenable to exon 53 skipping.
Enrollment Status: This study is recruiting participants at clinical sites in Europe.
More information: www.clinicaltrials.gov Identifier: NCT02310906
That's what caused FDA skepticism, delayed DMD drugs for 2-3 years. Only now if FDA internal opinion recovering to believe in dystrophin. Time for a make-up call on Eteplirsen by the umpires who blew the first 5 innings. Has already started with rolling NDA, may accelerate in next month.
Genocea 52% red in viral shedding. vical 19%
Genocea 48% reduction in genital lesions. vical 51%
Not clear why lesion reduction comparable or better, shedding less.
worth looking at some more data.
The PTC/BMRN had a table by an academic, not a rep of either co, showing how many exons were in clinical trials, Sarepta had 7, 2 more than anybody else. Sarepta, as Ed Kaye said at PPMD Connect Conference, is committed to getting therapy to as many treatable DMD boys as it can. SEVEN exons is more important than a lot of handwaving about 6MWT
because the regulatory path is too long. Go get em Ed.
PPMO versaility and specificity (Limited off target effects !!!!!!)
Using patient reported outcome measures
Regulatory approval pathways Accelerated Approval and Fast Track
If it worked for 12 patients, and it is shown safe for additional 20-30 patients, and. clear evidence shows that a drug produces a biochemical response that mitigates the serious disease then the benefit risk balance is positive.
don't know about herpes but vaccine space and specif DNA vaccine technology and adjuvants seems interesting in view of ACIP discussing H5n1 vaccine next week, widspread avian flu decimating poultry industry in US, and potential for new reassorts given large number of carriers/wild birds/pigs/turkeys etc/
Extends cash runway Last presentation Jun said $111 cash, expenses 65-80/yr, funds to mid 2016. Upfront $33 covers them to end 2016, NDA for HAE. Stockpile would be on top of that. BCX 4430, new targets BCXxxxx coming.
National End Duchenne Rally on Capitol Hill Steps, followed by meetings with legislators. 9-12:30 June 19
see PPMD Connect Conf Agenda
Interesting session could. be FDA Farkas on Jun 19 1:45 - can't say much specific but reemphasize FDA commitment to getting therapies to DMD community as soon as reasonably likely to show benefit , this after DMD demonstration on capitol steps in morning
See PPMD's comments about Biomarin getting rolling NDA filed on April 27
Suggests drug approval by 1Q 2016. A credible pathway, although always uncertain, is -mid year NDA complete, 3Q Advisory Committee, FDA approval within 6 months after AdComm.
The Duchenne community should celebrate. Today, Biomarin submitted the rolling NDA on drisapersen. This means we now have a second NDA submitted for Duchenne. Santhera is likely to follow soon. By first quarter 2016, we may see 3 approved drugs with more to follow. This is exactly what we have been working for, hoping for.
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,.