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DEADLINE TODAY - April 8.
The FDA hearing on expanding access to direct-acting-antivirals (docket FDA-2010-N-107) scheduled for april 30 has its first deadline today "Submit written or electronic requests for oral presentations and comments by April 8, 2010 (see section III of this document for details). Written or electronic comments will be accepted after the hearing until June 25,"
See http://edocket.access.gpo.gov/2010/pdf/2010-5055.pdf
For the many here who have been excluded by ifn-based tx (HectorSF, Susan400, MrLiver, Trinity4, JennyPenny,Smaug48, Magnum, MerryBe and many other friends) this could be a significant opportunity. The drug regime required to reach SVR among ifn-unresponsive or ifn-intolerant could well be within reach *now*, a combination of a polymerase inhibitor (r7128) , a protease inhibitor (boceprevir or telaprevir), an ifn-enhancer (alinia) along with tolerable levels of ifn/rbv.
The available clinical data on simultaneously targeting multiple viral proteins looks very promising and the approach has demonstrated success in HIV. However, drug manufacturers will not test this combination outside their own product line. The three companies currently testing polymerase/protease combinations (abbott, vertex, roche) are only testing their own drugs. Furthermore, they are testing in trials targeted at tx naive, not those most in need.
The FDA hearing is an investigation of whether additional trials, are appropriate:
"what types of studies should be conducted to best address unmet medical needs for patients with CHC including those with the greatest risk of progression of liver disease and/ or the lowest predicted virologic response rates"
The default path will be to only pursue regimes such as the one above after both a polymerase and a protease are approved and r7128 approval is very unlikely before 2014. Expanded early access to those most in need during the next 4-5 years could make a significant impact - let them know!
See http://edocket.access.gpo.gov/2010/pdf/2010-5055.pdf
For the many here who have been excluded by ifn-based tx (HectorSF, Susan400, MrLiver, Trinity4, JennyPenny,Smaug48, Magnum, MerryBe and many other friends) this could be a significant opportunity. The drug regime required to reach SVR among ifn-unresponsive or ifn-intolerant could well be within reach *now*, a combination of a polymerase inhibitor (r7128) , a protease inhibitor (boceprevir or telaprevir), an ifn-enhancer (alinia) along with tolerable levels of ifn/rbv.
The available clinical data on simultaneously targeting multiple viral proteins looks very promising and the approach has demonstrated success in HIV. However, drug manufacturers will not test this combination outside their own product line. The three companies currently testing polymerase/protease combinations (abbott, vertex, roche) are only testing their own drugs. Furthermore, they are testing in trials targeted at tx naive, not those most in need.
The FDA hearing is an investigation of whether additional trials, are appropriate:
"what types of studies should be conducted to best address unmet medical needs for patients with CHC including those with the greatest risk of progression of liver disease and/ or the lowest predicted virologic response rates"
The default path will be to only pursue regimes such as the one above after both a polymerase and a protease are approved and r7128 approval is very unlikely before 2014. Expanded early access to those most in need during the next 4-5 years could make a significant impact - let them know!
a couple of recent threads have flagged the same point. I'm resurfacing this one since it includes the link and directions for posting a comment. note the docket number must be included to associate your comment to the hearing. The hearing should be happening currently at Hilton Hotel, 1750 Rockville Pike, Rockville, MD 20852.. If anyone from the hcv support community is attending, it would be great to hear feedback.
As best I can tell, this is neither a political issue nor related to compassionate use. The seven questions they are requesting public comment on are :
"1. What types of patients with CHC are most appropriate for participation in DAA expanded access for CHC with regard to disease stage, previous treatment, and other disease characteristics?
2. Under what circumstances and in which populations would early access to a single DAA be appropriate?
3. Under what circumstances and in which populations would early access to multiple DAAs be appropriate?
4. How can pharmaceutical companies, government, academia, and community physicians and activists collaborate to provide for the treatment use of multiple new agents with the goal of maximizing response and reducing the emergence of drug or multidrug resistance?
5. What potential adverse reactions should be contemplated in formulating DAA treatment IND use protocols?
6. How can pharmaceutical companies, government, academia, and community physicians and activistscollaborate to provide for the treatment use of multiple new agents with the goal of maximizing response and reducing adverse reactions?
7. In the course of developing DAAs for marketing, what types of studies should be conducted to best address unmet medical needs for patients with CHC including those with the greatest
risk of progression of liver disease and/or the lowest predicted virologic response rates? Examples of studies thathelp to support clinical protocols or treatment use protocols in populations of unmet medical need may include renal and hepatic impairment studies and drug-drug interaction studies with antiretrovirals."
My read of the above was simply that they recognize that the current drug approval/release mechanism is inadequate in this area and are looking for ways to amend it. Comments will be accepted until June 25. There is an interesting comment posted by a SF pharmaceutical company but little in the way of specific patient input so far.
I've been trying to get some data on the size of the "warehoused" population before writing in my 2 cents; as I've posted, one of the main problems IMHO is that many nonresponders will jump into a soc+(1)DAA tx and develop resistance which could be avoided by widening access to soc +2DAAs. If anyone has data along those lines, please post - thanks.
As best I can tell, this is neither a political issue nor related to compassionate use. The seven questions they are requesting public comment on are :
"1. What types of patients with CHC are most appropriate for participation in DAA expanded access for CHC with regard to disease stage, previous treatment, and other disease characteristics?
2. Under what circumstances and in which populations would early access to a single DAA be appropriate?
3. Under what circumstances and in which populations would early access to multiple DAAs be appropriate?
4. How can pharmaceutical companies, government, academia, and community physicians and activists collaborate to provide for the treatment use of multiple new agents with the goal of maximizing response and reducing the emergence of drug or multidrug resistance?
5. What potential adverse reactions should be contemplated in formulating DAA treatment IND use protocols?
6. How can pharmaceutical companies, government, academia, and community physicians and activistscollaborate to provide for the treatment use of multiple new agents with the goal of maximizing response and reducing adverse reactions?
7. In the course of developing DAAs for marketing, what types of studies should be conducted to best address unmet medical needs for patients with CHC including those with the greatest
risk of progression of liver disease and/or the lowest predicted virologic response rates? Examples of studies thathelp to support clinical protocols or treatment use protocols in populations of unmet medical need may include renal and hepatic impairment studies and drug-drug interaction studies with antiretrovirals."
My read of the above was simply that they recognize that the current drug approval/release mechanism is inadequate in this area and are looking for ways to amend it. Comments will be accepted until June 25. There is an interesting comment posted by a SF pharmaceutical company but little in the way of specific patient input so far.
I've been trying to get some data on the size of the "warehoused" population before writing in my 2 cents; as I've posted, one of the main problems IMHO is that many nonresponders will jump into a soc+(1)DAA tx and develop resistance which could be avoided by widening access to soc +2DAAs. If anyone has data along those lines, please post - thanks.
the route for submitting comments electronically seems to be
1) got to http://www.regulations.gov/
2) click on submit a comment and enter the docket number followed by 0001 in the "Enter keyword or id" field:
FDA-2010-N-0107-0001
3) once the search finds the hearing, click on "submit a comment"
The final deadline is not until June 25th (and at the risk of making myself obnoxious I'll post reminders..). Have no idea how this process plays out (anyone familiar with it?) but it does look like a good opportunity. The drug companies are naturally concerned with demonstrating safety and efficacy of their respective products and getting them to market, so initiatives like the ones proposed are the only likely way to investigate multi-vendor combinations before approval.
There's clearly some risks - even though each of r7128/alinia/telaprevir/boceprevir has by now demonstrated safety on its own, unexpected side effects could result from the combination. Also, though resistance mutations to a combined polymerase/protease approach will likely be very weak (as suggested by the inform-1 data) this remains to be confirmed. Both these risks seem minor compared to the obvious risk of doing nothing.
Another possible consequence of the failure to make multiple DAAs available will be to promote sequential, unsuccessful single DAA attempts. The 1st gen protease inhibitors (telaprevir/boceprevir) are known to very "leaky" and thus dependent on a backup ifn effect. However, if they're the only option available, many non/null responders will try them after approval and resistance will complicate their use in later attempts.
1) got to http://www.regulations.gov/
2) click on submit a comment and enter the docket number followed by 0001 in the "Enter keyword or id" field:
FDA-2010-N-0107-0001
3) once the search finds the hearing, click on "submit a comment"
The final deadline is not until June 25th (and at the risk of making myself obnoxious I'll post reminders..). Have no idea how this process plays out (anyone familiar with it?) but it does look like a good opportunity. The drug companies are naturally concerned with demonstrating safety and efficacy of their respective products and getting them to market, so initiatives like the ones proposed are the only likely way to investigate multi-vendor combinations before approval.
There's clearly some risks - even though each of r7128/alinia/telaprevir/boceprevir has by now demonstrated safety on its own, unexpected side effects could result from the combination. Also, though resistance mutations to a combined polymerase/protease approach will likely be very weak (as suggested by the inform-1 data) this remains to be confirmed. Both these risks seem minor compared to the obvious risk of doing nothing.
Another possible consequence of the failure to make multiple DAAs available will be to promote sequential, unsuccessful single DAA attempts. The 1st gen protease inhibitors (telaprevir/boceprevir) are known to very "leaky" and thus dependent on a backup ifn effect. However, if they're the only option available, many non/null responders will try them after approval and resistance will complicate their use in later attempts.
Thank you willing. There hasn't been a day gone by since relapse that I haven't thought about how much longer do I have to wait and will my liver wait with me.
This is encouraging news.
Trin
This is encouraging news.
Trin
Thank you very much. This is an important opportunity for many of us. I hope they listen.
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