Det er efterhånden et stykke tid siden, at jeg ophørte med hver time at kontrollere, om FDA mon havde fået bragt orden i ODAC’s mødekalender samt uploaded dokumenter fra selve mødet d. 29/5 i tilgift til briefing dokumenterne. Som svar på min skriftlige forespørgsel meddeltes det at dokumenterne forhåbentlig ville være at finde på sitet efter 4-6 uger.
Siden da er der imidlertid sket noget, idet der nu linkes til FDA’s spørgsmål, således som de angiveligt blev forelagt ODAC, samt et sæt slides, der opsumerer de relevante data og issues fra briefingdokumentet.
Fortsat savnes dog et dokument der opsummerer afstemningen samt de deltagendes statements.
Final questions: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM167291.pdf
Slides: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM167289.pdf
Den ophedede stemning fra dagene op til og omkring mødet er vanskelig at genkalde sig, når man gennemser materialet, der selv i sin decimerede form (efter forkastelsen af den uafhængige komités ansættelse af ORR) fremstår overbevisende i sammenligning med de tilsvarende resultater for Fludarabine og Alemtuzumab (post Fludarabine), således som disse er oplistet i questions-dokumentet samt på slide nr. 4.
Jeg kan ikke erindre at have set disse resultater tidligere og er ret sikker på, at jeg den gang ville have knuget dem under min hovedpude, dersom jeg havde fundet dem i briefing-dokumentet.
Resultaterne er selvfølgelig ikke i sig selv nye, men det er dog nyt, at det er dem, der tilsyneladende er omdrejningspunktet for FDA’s syn på en godkendelse. Det er i hvert fald det indtryk, som efterlades i questions-dokumentet modsat briefing-dokumentet, der som bekendt beskæftigede sig med alle andre tænkelige spørgsmål om, hvorledes der kunne sås tvivl om resultaterne.
Ligeledes synes det at fremgå af pkt. 2 i questions-dokumentet, at de generelle spørgsmål vedr. vurderingen af CLL herunder anvendelsen af CT-scanninger netop er generelle, og at de som sådan i FDA’s øjne ikke har nogen direkte relation til godkendelsen af Arzerra. Dette var præcis hvad særligt Akademikeren argumenterede for, men hvilket desværre ikke fremstod særlig tydeligt i briefing-dokumentet.
Medmindre Arzerra viser sig at være indifferent over for tidligere anvendelse af Fludarabine og Alemtuzumab, og at resultaterne i CLL firstline dermed ikke overgår third line resultaterne, lover de opstillede Fludarabine og Alemtuzumab-resultater vel i øvrigt også godt for Arzerras chancer som first line behandling.
Den overordnede side med ODAC’s mødekalender og links til de øvrige dokumenter findes her:
http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/ucm126185.htm
Siden da er der imidlertid sket noget, idet der nu linkes til FDA’s spørgsmål, således som de angiveligt blev forelagt ODAC, samt et sæt slides, der opsumerer de relevante data og issues fra briefingdokumentet.
Fortsat savnes dog et dokument der opsummerer afstemningen samt de deltagendes statements.
Final questions: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM167291.pdf
Slides: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM167289.pdf
Den ophedede stemning fra dagene op til og omkring mødet er vanskelig at genkalde sig, når man gennemser materialet, der selv i sin decimerede form (efter forkastelsen af den uafhængige komités ansættelse af ORR) fremstår overbevisende i sammenligning med de tilsvarende resultater for Fludarabine og Alemtuzumab (post Fludarabine), således som disse er oplistet i questions-dokumentet samt på slide nr. 4.
Jeg kan ikke erindre at have set disse resultater tidligere og er ret sikker på, at jeg den gang ville have knuget dem under min hovedpude, dersom jeg havde fundet dem i briefing-dokumentet.
Resultaterne er selvfølgelig ikke i sig selv nye, men det er dog nyt, at det er dem, der tilsyneladende er omdrejningspunktet for FDA’s syn på en godkendelse. Det er i hvert fald det indtryk, som efterlades i questions-dokumentet modsat briefing-dokumentet, der som bekendt beskæftigede sig med alle andre tænkelige spørgsmål om, hvorledes der kunne sås tvivl om resultaterne.
Ligeledes synes det at fremgå af pkt. 2 i questions-dokumentet, at de generelle spørgsmål vedr. vurderingen af CLL herunder anvendelsen af CT-scanninger netop er generelle, og at de som sådan i FDA’s øjne ikke har nogen direkte relation til godkendelsen af Arzerra. Dette var præcis hvad særligt Akademikeren argumenterede for, men hvilket desværre ikke fremstod særlig tydeligt i briefing-dokumentet.
Medmindre Arzerra viser sig at være indifferent over for tidligere anvendelse af Fludarabine og Alemtuzumab, og at resultaterne i CLL firstline dermed ikke overgår third line resultaterne, lover de opstillede Fludarabine og Alemtuzumab-resultater vel i øvrigt også godt for Arzerras chancer som first line behandling.
Den overordnede side med ODAC’s mødekalender og links til de øvrige dokumenter findes her:
http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/ucm126185.htm
1/7 2009 20:10 Solsen 0
14587 Fra CS report:
Details of panel vote – when asked “Are the following results (Figure 3) reasonably likely to predict clinical benefit in patients with CLL that is refractory to fludarabine and alemtuzumab?”
Panel member Vote Panel member justification
William Kelly D.O
Yes
I think it does show clinical activity that will translate to clinical benefit down the road, the only concern I have is to
make sure safety is monitored in the future
Ronald Richardson M.D
No
I voted no mainly because I think the data that are being presented here are not robust enough to support accelerated
approval. I guess I would prefer to wait for the results of the phase III studies.
David HarringtonPh.D.
No
I voted no. I think the amount of noise in this study makes it very very hard for me to assess what the real benefit is
here. I think despite the obvious unmet need I think this is exactly the situation where a randomised trial is needed to
understand the benfit of a therapy. There are just too many things here that add uncertainty to accelerated approval.
Michael Link M.D
Yes
I voted yes. When you have to read a four page paper just to understand what response is it obviously demonstrates
the difficulty in assessing what response is. Despite that, I am convinced that a response rate for an anti-CLL effect
was definitely demonstrated and i think that patients will benefit in terms of symptom control and other things that are
related to disease even if they dont have prolongation of survival
Gail Eckhardt M.D
Yes
I voted yes. I agree that the results as presented do have a reasonable likelyhood of predicting clinical benefit. I think
it’s a complex disease with even more complex response criteria that are probably going to require further
modifications. And I think probably one of the main next steps for this disease is going to be in designing ways in
which we can more definitively assess response in the refractory patient.
Gary Lyman
Yes
I voted yes for the reasons previously stated and I am reasonably reassured by the magnitude and the fact that
despite all the uncertainties around measurement and response assessment discussed here, there is a reasonable
likelyhood of clinical benefit from the data presented but as stated by others, safety concerns remain along with
confirmation in phase III trials that need to move forward quickly.
Jean Grem M.D FACP
Yes
I voted yes even though I had a lot of concerns about the trial, I think that when they had their discussions they
thought that using the agreed upon criteria if they hit more than 20% response that that would be considered evidence
of presumed clinical benefit, so i voted yes.
Wyndham Wilson M.D
No
I voted no, I felt that there was too much uncertainty in this study and I also felt that when one looks rigorously at the
data comparing it to those who did not respond, it is unclear that there is benefit overall and also when one looks at
historical data the data looks remarkably similar in terms of overall survival. So whereas i think there certainly may be
benefit of this drug i think that it does not reach the level to justify accelerated approval but i feel more comfortable
waiting for a randomised study
Margaret Tempero M.D
Yes
I voted yes, in addition ot the other positive statements that have already been made I was impressed by the
resolution of symptoms in this patient population which we really didn’t discuss that much but it is far greater, I believe,
than one could expect with a placebo controlled trial for instance and also i felt that the overall survival benefit actually
did look encouraging compared to historical data
Virginia Mason RN
Yes
Based on the information that has been provided I would like to see accelerated approval and hopefully that new trials
will show that this is indeed a good choice and that the safety profile remains good
Diane MacKinnon
Yes
I voted yes, I felt that the presentation fulfilled the requirements for accelerated approval and I hope to welcome this
drug as an addition to the very limited arsenal of therapy available to a subset of CLL patients
Julie Vose M.D
Yes
I voted yes. I believe that the information does provide hope for patients with very limited choices and I do have
concerns about some of the issues we talked about. The confirmatory phase III trials need to be done as soon as
possible and also use some of the new criteria and then i hope that we can confirm the results
Carole Miller M.D
Yes
I voted yes. It is an unmet clinical need and it did show evidence of clinical benefit with all the provisos that we
discussed previously
Details of panel vote – when asked “Are the following results (Figure 3) reasonably likely to predict clinical benefit in patients with CLL that is refractory to fludarabine and alemtuzumab?”
Panel member Vote Panel member justification
William Kelly D.O
Yes
I think it does show clinical activity that will translate to clinical benefit down the road, the only concern I have is to
make sure safety is monitored in the future
Ronald Richardson M.D
No
I voted no mainly because I think the data that are being presented here are not robust enough to support accelerated
approval. I guess I would prefer to wait for the results of the phase III studies.
David HarringtonPh.D.
No
I voted no. I think the amount of noise in this study makes it very very hard for me to assess what the real benefit is
here. I think despite the obvious unmet need I think this is exactly the situation where a randomised trial is needed to
understand the benfit of a therapy. There are just too many things here that add uncertainty to accelerated approval.
Michael Link M.D
Yes
I voted yes. When you have to read a four page paper just to understand what response is it obviously demonstrates
the difficulty in assessing what response is. Despite that, I am convinced that a response rate for an anti-CLL effect
was definitely demonstrated and i think that patients will benefit in terms of symptom control and other things that are
related to disease even if they dont have prolongation of survival
Gail Eckhardt M.D
Yes
I voted yes. I agree that the results as presented do have a reasonable likelyhood of predicting clinical benefit. I think
it’s a complex disease with even more complex response criteria that are probably going to require further
modifications. And I think probably one of the main next steps for this disease is going to be in designing ways in
which we can more definitively assess response in the refractory patient.
Gary Lyman
Yes
I voted yes for the reasons previously stated and I am reasonably reassured by the magnitude and the fact that
despite all the uncertainties around measurement and response assessment discussed here, there is a reasonable
likelyhood of clinical benefit from the data presented but as stated by others, safety concerns remain along with
confirmation in phase III trials that need to move forward quickly.
Jean Grem M.D FACP
Yes
I voted yes even though I had a lot of concerns about the trial, I think that when they had their discussions they
thought that using the agreed upon criteria if they hit more than 20% response that that would be considered evidence
of presumed clinical benefit, so i voted yes.
Wyndham Wilson M.D
No
I voted no, I felt that there was too much uncertainty in this study and I also felt that when one looks rigorously at the
data comparing it to those who did not respond, it is unclear that there is benefit overall and also when one looks at
historical data the data looks remarkably similar in terms of overall survival. So whereas i think there certainly may be
benefit of this drug i think that it does not reach the level to justify accelerated approval but i feel more comfortable
waiting for a randomised study
Margaret Tempero M.D
Yes
I voted yes, in addition ot the other positive statements that have already been made I was impressed by the
resolution of symptoms in this patient population which we really didn’t discuss that much but it is far greater, I believe,
than one could expect with a placebo controlled trial for instance and also i felt that the overall survival benefit actually
did look encouraging compared to historical data
Virginia Mason RN
Yes
Based on the information that has been provided I would like to see accelerated approval and hopefully that new trials
will show that this is indeed a good choice and that the safety profile remains good
Diane MacKinnon
Yes
I voted yes, I felt that the presentation fulfilled the requirements for accelerated approval and I hope to welcome this
drug as an addition to the very limited arsenal of therapy available to a subset of CLL patients
Julie Vose M.D
Yes
I voted yes. I believe that the information does provide hope for patients with very limited choices and I do have
concerns about some of the issues we talked about. The confirmatory phase III trials need to be done as soon as
possible and also use some of the new criteria and then i hope that we can confirm the results
Carole Miller M.D
Yes
I voted yes. It is an unmet clinical need and it did show evidence of clinical benefit with all the provisos that we
discussed previously
