Tuesday, September 15, 2015

Interesting Statements -- Back When FDA Approved Propecia® (Finasteride) For Hair Loss -- By Dr. Imperato-McGinley

Back when Merck originally sought FDA approval of finasteride for the indication of male pattern baldness, the doctor appeared at the Advisory Committee hearing and spoke for the company. [Merck by then already had obtained FDA approval for prostate enlargement, under the brand name Proscar® -- but baldness was a much wider market.] She generally noted the safety of the drug candidate for that purpose, and apparently made reference to her earlier work in the Dominican Republic. I mention this because that is what our erstwhile anonymous commenter was pointing to, in the cogent comment to my last post on this topic. Her statements to FDA, on behalf of Merck do make her a likely witness to these matters, in my estimation. So she is likely to be asked quite a few more questions, as discovery rolls forward. She ought to get used to it.

To be fair, though, the FDA still feels that sexual dysfunction is a relatively rare side effect. To wit, recently, the FDA has cleared an update to the finasteride label, and weighed in on these topics. From FDA then, a bit:

. . . .Q5. Do all men experience sexual adverse events when using Propecia or Proscar?

A5. No. Only a small percentage of men using these drugs have experienced a sexual adverse event. The frequency of sexual adverse events is best obtained from controlled clinical trials. Analysis of these controlled clinical trials showed that during treatment with Propecia, 36 (3.8%) of 945 men had reported one or more adverse sexual experiences as compared to 20 (2.1%) of 934 men who did not receive Propecia (received placebo).

Sexual adverse events associated with Proscar use were identified in two clinical trials. This information is included in the Proscar label. In one trial, these events were reported more frequently during the first year of treatment with Proscar as compared to men who received placebo. In years 2-4 of the trial, there was no significant difference between treatment groups in the incidences of impotence, decreased libido and ejaculation disorder. . . .

It should be noted that the Proscar studies mentioned above generally involved much older men -- in short, men more likely to be on other medications which might mask the alleged off-target effects -- as those men might well already be experiencing sexual decreases -- even from the passage of time. The same was generally not true of Propecia candidates -- they tended to be younger and healthier, and so (the plaintiffs' argument runs) were more likely to notice and report any sexual side effects. We shall -- as ever -- see.

UPDATED: 1 PM EDT | 09.15.2015 -- To make the record complete, here is the full five page PDF of the November 19, 1997 Merck letter to FDA that our erstwhile anomymous commenter points us to -- and an image of the part I personally found most interesting, though the opinions of Dr. Imperato-McGinley are quoted a few other times, in that letter:

And still we have no idea what transpired on Thursday, September 10, 2015 -- in Brooklyn. There has been no update to the electronic record, through noon Eastern, here on Tuesday. So. . . onward, with a big smile.


Anonymous said...

Any theories as to why there's no update from Brooklyn yet? - Mr. I

Condor said...

Thanks Mr. I -- I haven't a clue.

But it isn't that unusual -- it sometimes takes weeks to get a minute order together, if the rulings from the bench that day were complicated (or contentious).

And if nothing momentous occurred, the minute order may only indicate "hearing held" -- and the time in court, on the record.

Patience is a virtue here (in the remote reporting of federal District Court MDLs), indeed.

Namaste, my friend.

Anonymous said...

Interesting posting! I took a look at this cited document source and found that there appeared to be large volumes of communications between MRL and the FDA between the dates of September 26, 1997 thru December 11, 1997 and December 11, 1997 thru December 19, 1997. I felt therefore it deserved a closer look.

Intriguingly and to my surprise, the latter period appeared to focus around data reporting, results and conclusions belonging to a nebulous study titled '#94'[most reporting in the Medicine Officer's Review in Section: has been removed with white-out] and the end results of these discussions lead to laborious 'Labeling' negotiation between both parties.

Interesting also was that the safety results from the PLESS study (Long-term Proscar) were submitted in the supplemental drug application NDA20180/S16 for Proscar on September 19, 1997. The results of these data (analyzed in NDA20180/S16) do not appear very shocking, rather two sentences within the Methods section of the published study gave me a new pair of reading glasses. It reads: "One site at
which 24 men had been enrolled was closed prematurely because of inadequate study documentation. The results for these men were included in the safety analysis.."[1]

hummm.... and "Merck believes that the safety issues have been largely addressed in NDA 20-180 (Proscar (TM)).."[2].


[2](FDA NDA 20788)Amendments to Pending Application Received November 12 & 20, 1997: Merck's Perspectives Discussed at Advisory Committee Meeting of 11/19/97.