Re: Waiting for Genasense ~ a case in point

[Guest guest]

Sorry I forgot to add this link to an article that gives a timeline

to the ODAC-Genasense approval process...

http://www.oncbiz.com/documents/OBR_0108_Genasense(1).pdf

~chris

[Guest guest]

Hi Be aware that the link is to a business perspective, which could well

be biased - the WSJ consistently bashes FDA on evidence standards in its

editorials.

In contrast the advisory committee members are vetted for financial conflict of

interest.

I attended as an observer and don't recall the main issues, but these are

provided by fda in summary form.

http://www.fda.gov/ohrms/dockets/ac/06/minutes/2006-4235m1-01.pdf

Be aware that most drugs don't go before ODAC - only the close calls, and

sometimes more data is requested based on the issues raised.... which delays the

decision ... be aware the sponsor is apt to present (through the media) the data

selectively ... and downplay or leave out the issues of concern to the

reviewers. And FDA must be quiet about the rationale for rejection although

that might change - and should change IMO.

Karl

>

>

> Sorry I forgot to add this link to an article that gives a timeline

> to the ODAC-Genasense approval process...

>

> http://www.oncbiz.com/documents/OBR_0108_Genasense(1).pdf

>

> ~chris

>

[Guest guest]

Sure Karl, I understand the point you make about bias.

Irregardless, we don't have approval of Genasense after an inordinate length of

time.

~chris

-> Hi Be aware that the link is to a business perspective, which could

well be biased -

[Guest guest]

Hi

Unfortunately, it may be that G will never win approval because of issues with

the results - in this case a close call ... requiring a public hearing and ODAC

review, leading to rejection or a delay to allow the sponsor to provide more

follow-up data.

Copying from the FDA summary, only the toxicity issues:

" The addition of Genasense to the fludarabine plus cyclophosphamide regimen is

associated with increased toxicities, including increased numbers of severe AEs

and serious AEs and more nausea, vomiting, fever, fatigue, blood transfusions,

and bleeding.

Genasense administration requires an indwelling central venous access device for

continuous intravenous infusion and an external infusion pump (or

hospitalization) for 7 days monthly.

Infusion catheter-related complications occurred in 16% of the Genasense

patients, including catheter infections and venous thromboses, compared to a 3%

rate in the control arm. "

So these are not issues the sponsor is likely to emphasize in its press

releases. And as I recall there were more deaths in the G arm, but it might not

have been statistically significant.

It seems worth noting that the active control (FC without R) is/was substandard

to FC+R... (which would not block approval if the evidence was convincing).

So would CLL patients -- fully informed about the benefit/risk profile of

Genasense (G) -- go with FC+G or FC+R (Rituxan)?

Noting that FCR was a clear winner over FC ... and so if G was approved for

marketing, how to use it would still be an unanswered question, requiring more

testing, without which it might not be used much ....

Karl

>

> Sure Karl, I understand the point you make about bias.

>

> Irregardless, we don't have approval of Genasense after an inordinate length

of time.

>

> ~chris

>

>

>

> -> Hi Be aware that the link is to a business perspective, which could

well be biased -

>