Read the Reuters article about Bowing to Political Pressure, FDA to reform opioid approval. The Commissioner nominee, who agreed to hold committee meetings on addictive drugs and their approval, said policy pressure helps them think, but that FDA cannot be politically pressured on specific drug decisions. So, just be careful, make reasoned arguments, address the data, backed up with responsible experts. The panel from the Oct 1 presentation will be listened to if presented -Connolly, Sieh, Wilton,
Amendment to Sole Source Justification Memo
Notice of Intent to Sole Source Antiviral Oseltamivir (Tamiflu) - AG-6395-S-16-777141 February 3, 2016
This Amendment incorporates the following changes:
1. Paragraph 6, Market Research, has been revised to read as follows:
“Market research was performed in order to support the planned purchase of Tamiflu for the National Veterinary Stockpile (NVS). Market research found that in addition to Tamiflu, there are four other types of antiviral medicines – zanamivir, amantadine, rimantadine, and peramivir. During the 2015-2016 flu seasons, CDC distributed a health alert about the resistance of influenza viruses to amantadine and rimantadine and made a recommendation that oseltamivir (trade name Tamiflu) or zanarnivir (trade name Relenza) be selected if an antiviral medicine was used for the treatment and prophylaxis of influenza. Tamiflu and Relenza were the two FDA- approved influenza antiviral drugs recommended by the CDC. http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
CDC currently recommends oseltamivir, peramivir, or zanamivir for treatment of human infection with avian influenza A viruses. http://www.cdc.gov/flu/avianflu/prevention.htm
$8-12 billion for core, to Verizon, Google, others. Gives additional $10 per share minus taxes to existing $6/share in cash, remaining business has BABA plus say $12/share in cash. Valuation $32-42/share after sale. More if a more tax efficient sale can be arranged.
Before, during or after the PPMD 2016 Advocacy meetings? Maybe 24-26, which is of course right next to
the current PDUFA date. Have the feeling the FDA doesn't want to screw this up again, so AdCom date and any revised PDUFA data would all come together. And another thing, if there is any likelihood of approval, they've got to be getting the labeling down, so there isn't a delay to work out labeling before making
eteplirsen available to the Exon 51 amendable patient community.
The conference is open to all members of the Duchenne community. For members of Industry, we welcome your participation in our training session on Sunday as well as at the morning policy session on Monday. Industry members will not be scheduled for hill meetings with Advocates.
Sunday, February 21nd, 3pm-7:30pm - Advocate training
Monday, February 22nd, 9am-5pm - Hill meetings
Tuesday, February 23rd, 9am-5pm - Hill meetings
From Stahl, Jacob, History of Accelerated Approval
The Lasagna Commission also criticized a high efficacy threshold, echoing Katzman’s concerns that it had needlessly slowed down the drug approval process. Arguing that terminally ill patients, in consultation with their doctors, should be able to elect to assume a higher level of risk, the Commission cited the Senate Report on the 1962 Drug Amendments, which stated, “In such a delicate area of medicine [where there is a difference of opinion as to whether or not the drug is effective], the committee wants to make sure that safe new drugs become available for use by the medical profession so long as they are supported as to effectiveness by a responsible body of opinion and scientific fact.” The Commission therefore contended that the FDA should not be the ultimate arbiter of effectiveness, but rather should leave the patients the option of taking risky treatments if they would otherwise likely die.
The experts who may testify at the Advisory Commission-we don't know who they will be, but if its a lineup like Wilton, Mendell, Muntoni, Kunkel, would provide "a responsible body of opinion." and their discussion of the data would establish the necessary scientific fact - consistent trends on dystrophin production +; 6Mwt + LOA + pulmonary function + a consistent set of data showing improvement versus the course of the disease if left untreated. So clinicians and then, of course, the patients and PROs.
RNA polymerase is essential for the replication of numerous RNA viruses (te Velthuis, 2014). BCX4430, a novel nucleoside analog, is an inhibitor specific for viral RNA polymerase and exhibits broad-spectrum antiviral activity against viruses including filoviruses, flaviviruses, arenaviruses, paramyxoviruses, coronaviruses, and bunyaviruses (Warren et al., 2014). BCX4430 treatment completely protected golden hamsters from death caused by infection with YFV (flavivirus)
i can see not choosing peramivir because of documented medical need for gel cap. but discussing antivirals without mentioning peramivir and instead discussing amantidine seems shoddy work. not to mention. it will put those animal inspectors at risk because tamiflu isn't the strongest available MCM
FBO Notice to procure tamiflu for SNS to protect APHIS and veterinary people from avian flu doesn't even acknowledge peramivir in discussion of influenza antivirals. Clueless govt functionaries under thumb of big pharma. Responses due Feb 6
Wheelchair use, or loss of ambulation, are not the fundamental interim clinical endpoints. The production of dystrophin (or not) and the 6Mwt are the intermediate clinical endpoints, observable earlier than irreversible morbidity, on the basis of which Accelerated Approval is sought. Dystrophin is particularly important, which is the reason why it is the first topic in the FDA briefing memo.PDPF shows a trend toward increased dystrophin, which translates into benefit, reasonably likely to occur. Timed walking, not loss of ambulation, is the
second. And as to the claimed bias in the FDA briefing document, they are doing what they explain, if a historical control is used, you have to examine all the potential sources of explanation for differences in the endpoints other than drug effect. And I don't support comments attacking members of the FDA staff for doing their job - its not ad hominems but rational discourse citing evidence that will determine the approval or not.
But at the end, its up to the Advisory Committee. p. 33
Thus, as you digest the background materials, we hope you will carefully consider the strengths and weaknesses of all of the data, and be prepared to consider and discuss whether or not you believe that efficacy has been established.
The pertinent Code of Federal Regulations sections 324.126, have a discussion of what adequate and well controlled studies, and criteria for studies in section b, and a subsection b(v) using historical controls, which basically says only for unusual circumstances like predictable mortality.....
you think Duchenne Muscular Dystrophy qualifies??, so historical controls can work,
and then there is section 324.126 (c) which says the Director of CDER can waive any of the b criteria, for a proposed, or "completed study"on own initiative or petition, if informed why the criteria are not reasonably applied to a specific clinical trial, and what evidence the trials showed as substantial evidence. Perhaps why
Woodcock will be in attendance to hear all the presentations, including FDA, Sarepta, Sarepta's addendum, the patients, and the experts. The FDA may take, serious disease, unmet medical need, evidence of dystrophin production, 6mwt boys still walking, flexibility, confirmatory studies and patient reported outcomes and expert advocacy and do something reasonable. with Exondrys51.
FDA is announcing the availability of a guidance for industry entitled “Guidance on Qualification of Biomarker—Galactomannan in Studies of Treatments of Invasive Aspergillosis.” In theFederal Registerof October 27, 2014 (79 FR 63921), FDAannounced the availability of a draft guidance entitled “Draft Guidance on Qualification of Biomarker—Galactomannan in studies of Treatments of Invasive Aspergillosis.” The Agency received one comment during the public comment period which was supportive of the qualification of this biomarker. This guidance finalizes the draft guidance issued in October 2014.
FDA got: Dystrophin measured by 3 independent labs; matched natural history showing +151 6Mwt, safety data from 12, then 42, now 111 boys beind dosed in confirmatory and other exon trials. FDA Farkas, have complete package of requested data showing efficacy, then benefit/risk ratio highly favorable. Eteplirsen approval before PPMD marches on Washington Feb. 22-24
Could be they need an AdCom to verify/validate the labeling. FDA guidance on labeling for drugs with Accelerated Approval says labeling will discuss uncertainty of benefits and ongoing confirmatory studies. In his fireside chat, I believe Dr. Kaye said they would be discussing labeling about a month before the PDUFA date, which is about the time of the AdCom. So there will be two things going on, the public thing (AdCom) and the
background thing (labeling of AA drug).
Is there an official name to this solicitation? Would MCS like the Offeror to use descriptive name based on our unique offering, the FBO post title, another official name, or just the solicitation number for our proposal title? Please reference the solicitation number, W911QY-16-R-0002-Antiviral.
100% of patients dosed with eteplirsen showed exon skipping by RNA sequencing - slide 26 of Oct 1 briefing
100% of patients dosed with eteplirsen in completed clinical studies to date demonstrated exon skipping (N=36)
Regulatory authorities approve drugs that are demonstrated to be safe and effective for human use. The meaning of "safe" has historically been interpreted to mean that the benefits of the drug outweigh its risks. This benefit-risk assessment of pharmaceuticals is the fundamental basis of regulatory decision-making. In the last several years, providing greater structure for the benefit-risk assessment has been an important topic in drug regulation.
One advocate's testimony to ADCom published Nov 27 at JettFoundation - so don't know if your scenario is right, but there will be very serious consideration for Eteplirsen on basis of safety, need and efficacy.
Had Jett remained on drug, by my own estimate, he would have 250 of these injection sites. There is no way Jett could “manage” this risk.
And in the context of all of the safety risks that you have heard about today, these are the least severe.
So as you deliberate, please remember:
The risk to patients like Jett is not “manageable”
For patients like Jett who are exon 51 amenable, we need other options
And for all those patients in our community, who are not exon 51 amenable, the unmet need remains and is significant
2) Upon filing for renunciation the IRS will take half of your wealth
If you have a net worth less than $2 million and don’t meet the IRS income test after giving up US citizenship, you automatically owe no exit tax. If your net worth is over $2 million, you are what the IRS calls a “covered expatriate,”