Investigate the Colman/Orloff Connection

I urge caution with accusations

Below is a post from YMB which is interesting yet questionable, some of the accusations are strong and not sure if proofs exist. This might be good story for some investigative journalist to pursue.

Check this link to Adcom meeting from 2004 where Colman and Orloff presented and worked very closely


http://www.fda.gov/OHRMS/DOCKETS/AC/04/transcripts/2004-4068T1.htm

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Post by "knospeaba_robert"

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If this is looked into, i am sure it would lead back to the fact that the Qnexa study writer Dr. Orloff and Dr. Colman have connections that would lead one to see foul play as possible specifically based on Colman's actions surrounding the Qnexa and Lorq panels. This was posted on the MB and I hope someone here puts some time into following up and if correct, posting it on the Deepcapture blog. To me this is the smoking gun issue at hand and serves to motivation, the only thing (other than the idea of money) that we have to show why there would be a bias.

Evidence suggests that Orloff and Colman worked closely together while at the FDA (not only on obesity related matters):

David Orloff and Eric Colman worked together on the 2004 Report of the Working Group on Obesity -
FDA Obesity Working Group Subgroup Members
THERAPEUTICS - Lead: David Orloff. Members: Eric Colman, Patricia Beaston

http://www.fda.gov/OHRMS/DOCKETS/AC/04/transcripts/2004-4068T1.htm


Eric Colman had authority to sign some documents for David Orloff. For examples:
see page 9
http://www.accessdata.fda.gov/drugsatfda...
see page 3
http://www.accessdata.fda.gov/drugsatfda...

When Orloff caused an FDA scandal he immediately found a new position at Medspace. Was this payback to Orloff for his controversial decisions and a deflection from a proper investigation?

New York Times article - December 7, 2005
A Food and Drug Administration official whose office was involved in a recent controversial application for drug approval said yesterday that he was resigning to join private industry. Dr. David Orloff, a division director who oversees the review of drugs to treat metabolic and endocrine disorders, is set to join Medpace, a contract research organization based in Cincinnati that runs clinical drug trials.
http://query.nytimes.com/gst/fullpage.ht...

Orloff was involved with qnexa at Medspace, but the level of involvement is not entirely clear:
Dr. David Orloff and his staff at Medpace, the clinical research organization that managed the qnexa clinical trials…
http://www.health2sport.com/patients-on-...

VVUS’s obesity clinical trials are being led by Dr. David Orloff, former director of the FDA’s Division of Metabolic and Endocrine Drug Products
http://obesityinvestor.typepad.com/obesi...

Dr. David Orloff, former head of the FDA’s Endocrine and Metabolism Division helped Vivus craft a data package that has a high likelihood of passing the scrutiny of the FDA.
http://www.investorvillage.com/smbd.asp?...

While at Medspace, Orloff believed that the FDA guidelines for combination drugs was irrelevant:
Dr. David Orloff served as the Director of the Division of Metabolism and Endocrinology Products at FDA from 2000-2006. Dr. Orloff felt that investors were over-interpreting FDA obesity guidelines. He believes that data to date shows qnexa to be very well tolerated and very effective, asserting that nothing so far should "sound any alarms." Dr. Orloff feels the issue of combination synergy (demonstrating 2x the weight loss of individual components) that has plagued VVUS is “ridiculous” and should “in no way be considered a requirement for approval."
http://www.investorvillage.com/mbthread....

Did he believe the FDA guidelines were irrelevant for assessing qnexa because Colman (his former close associate) was now responsible for reviewing NDAs? Orloff may have groomed Colman in how to game the approval process? The appearance of a conflict of interest gets worse... 

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Copied from YMB which was posted by "erewenguy"

There has been ongoing conversation in the comments section of one of Herper's latest articles.

http://blogs.forbes.com/matthewherper/2010/10/28/vivus-diet-drug-denied/#comment-1353

The accusations were called a "conspiracy theory", so I tried to outline the situation as I see it.

...

The “conspiracy theory” arises when looking at the total picture. If this were a court of law, enough circumstantial evidence exists for a grand jury to issue an indictment. Events are presented chronologically with the best information I have:

I believe Gebbe or his associates published the first information on the topo/phen combination in 2003 (?).

The FDA obesity workshop was conducted in 2004, where Orloff was chair of the theraputics subcommittee, which included Colman. It was time to advance the concept of combination therapies. Orloff and close associate Colman are on the regulatory “cutting edge” of understanding obesity theraputics.

Orloff’s office approves qnexa trials. Orloff’s office apparently recommends monotherapy trials of lorcaserin – a modification of a discredited drug.

Orloff becomes involved in controversy over approving a drug found to be dangerous (a questionable approval).

Orloff resigns from FDA and accepts a position at Medpace, where he oversees qnexa clinical trials his office approved.

Orloff publicly states that although qnexa DOES NOT meet combination therapy efficacy guidelines, there is no reason to believe it will not be approved.

Orloff writes qnexa NDA for Vivus, who submits it to FDA-CDER (Colman's office)

Colman is a guest on a television show which features Qnexa.

Qnexa panel review is conducted with proper diligence. “Abstain” IS allowed to panel members as a valid vote. Panel recommends rejection (no abstains) and Colman is on public record that he is surprised by the recommendation.

Lorcaserin panel meets, with well documented omissions or errors in regards to science and FDA guidelines for toxicity and efficacy, and conducted with biased innuendos and comments by FDA personnel Colman and Rosebraugh throughout the meeting. Critical cancer and toxicology experts are not on the panel. During voting instructions “abstain” is explicitly NOT allowed as an option. Panel members express ignorance of cancer/risk issues and vote to reject in the absence of abstain option.

Lorcaserin CRL is issued by Colman's office. ARNA to request type A meeting to clarify FDA requirements for path to approval.

Qnexa CRL issued by Colman's office. VVUS will respond in 6 weeks. No clarifications are needed concerning path to approval.

...

There are other side-bar facts to fill out the drama, such as potential document leaks and options activity, but the information presents the highlights.

I’m really not a conspiracy theory kind of guy, so I would welcome an alternative viewpoint compatible with Occam’s razor.


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Response by "diogenes_32bc"

Here's what JL said at the BMO conference (this was after the July EMDAC) in response to a question on LorPhen:

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RE: Lorcaserin-phentermine study:

JL: You know, in the past, when I asked the FDA that question, they were not in favor of such a study... they discouraged that study... and we've recently seen what another company with phentermine as part of their product... some of the liabilities that phentermine brings to that product in terms of heart rate and pressure effects... and that sort of thing... so we're flexible, we're open, we'll have a dialog with the FDA later on... I should mention that phentermine is not available in Europe at all, it's not available in Canada, I don't think it's available in Japan... so it's certainly not.. something that's cookie-cutter way of losing weight throughout the world... so we'll just have to see.. how that works out... and I should also mention that since we'll be doing these agreements with countries throughout the world, we'll look at the local regs and that sort of thing.
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This is not verbatim, and is most likely not the final word on this so keep it in context.

==========================gopher_post============================

All fair questions raised by "gopher_tunnel"

“The FDA obesity workshop was conducted in 2004, where Orloff was chair of the theraputics subcommittee, which included Colman.”

Who else was in on that workshop? Do any of those names appear other places of interest?

“Orloff’s office approves qnexa trials. Orloff’s office apparently recommends monotherapy trials of lorcaserin – a modification of a discredited drug.”

What was Orloff’s role in this? Further documentation needed.

“Orloff resigns from FDA and accepts a position at Medpace, where he oversees qnexa clinical trials his office approved.”

Did he actually oversee Qnexa trials? Such a charge would need to be substantiated.

“Orloff publicly states that although qnexa DOES NOT meet combination therapy efficacy guidelines, there is no reason to believe it will not be approved.”

Link?

“Orloff writes qnexa NDA for Vivus, who submits it to FDA-CDER (Colman's office)”

Did Orloff write the NDA? Proof?

“Qnexa panel review is conducted with proper diligence. “Abstain” IS allowed to panel members as a valid vote. Panel recommends rejection (no abstains) and Colman is on public record that he is surprised by the recommendation.”

Link to Colman’s comments?

“Lorcaserin panel meets, with well documented omissions or errors in regards to science and FDA guidelines for toxicity and efficacy, and conducted with biased innuendos and comments by FDA personnel Colman and Rosebraugh throughout the meeting. Critical cancer and toxicology experts are not on the panel. During voting instructions “abstain” is explicitly NOT allowed as an option. Panel members express ignorance of cancer/risk issues and vote to reject in the absence of abstain option.”

Untrue. “Abstain” WAS an option but the panelists were pressured repeatedly to vote “yes” or “no”.

The theory may be correct, but the case requires more detail.

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========================gopher post============================