Wednesday, January 14, 2009

Another Day -- Another Unfavorable FDA Letter -- Received by Schering. . . .


While this Asenapine delay may turn out to be rather short -- it is also quite possible that FDA will "not like what it sees" ["Cue Salmon, stage left" -- paging Salmon!] in the additional data sets it has requested for Asenapine -- one of Schering's much vaunted "Five Stars" -- now about two years behind the earlier-scheduled US launch date.

This morning's FDA complete response letter comes only one day after the proposed "Over The Counter", or OTC, form of Omeprazole, received an even more unfavorable FDA complete response letter. Wow. That looks like an emerging pattern, here.

More plainly put, it is -- in my experience -- additional evidence that FDA now eyes rather warily every submission from Schering -- given the less than forthcoming nature of the ENHANCE results release-delays, then the attempt to downplay those same results. For what it is worth, Schering is pleased that the letter represents -- it hopes -- only a shortish delay:

. . . .We are pleased with the progress on the Saphris filing and look forward to working with the agency to address its request, finalize the product labeling and gain approval," Thomas Koestler, president of the Schering-Plough Research Institute, said in a statement. . . .

Okay. Right. Check. . . .

9 comments:

Nathan said...

Condor, I get the distinct impression that you are rooting FOR the failure of SP products and profits. You write some interesting posts. But I get them impression that you are hoping that SP's drugs will crash and burn. That's irresponsible and inhumane. Is there any SP product that you are hoping will succeed? Or do you just hope that SP just crashes and burns along with the rest of the pharma industry?

Even if you hate the past behaviour of these companies, it seems that (as a human) you would be in favor of effective products being delivered onto the market....

Anonymous said...

Oh boy is SP and FDA's approach elegant. It may take me a few days to pull together a complete response.

Salmon

P.S. I'm not routing for anyone to crash and burn. I simply want truthful evaluation and appropriate labeling. Unfortunately when people prevent that, apparently in order to maximize inappropriate usage it drags out the entire process unnecessarily and I believe it's detrimental to companies in the long run.

Condor said...

Hey Nathan, thanks for the feedback -- and, like Salmon (who arrived here, before me) -- to answer yours:

". . .That's irresponsible and inhumane. . ."

First, I am not rooting "for" Schering's demise -- I am "rooting for" HONEST, ETHICAL, CANDID management -- at Schering. In short, new management.

It could (once again) be a great company, if the current "culture of deception and usurious profit-first-medicine, by putting quarterly results way ahead of good science" were to be rooted out. [BTW -- What else would explain the 10X pricing of the only-as-good-as-a-generic-statin-Vytorin?]

If -- in your view -- it is inhumane (of me) to root for the removal of the "$30 million man": CEO Hassan, and the rest of his grossly overpaid Top Six, well. . . so be it.

I want this management team removed for gross incompetence, negligence and breach of fiduciary duties to the sharelholders.

That is not irresponsible or immoral -- in my book. Moreover, the notion that I am against "effective products" entering the market -- because I think Fred Hassan is dishonest is, well. . .

s i l l y.

Silly, in the extreme.

Namaste

Nathan said...

Condor writes: "It could (once again) be a great company..."

I'd like to ask you specifically about the "once again" phrase. In your opinion, when was SP a great company?

You almost seem like a "reverse-cheerleader" -- you take delight in pharma's failures. It's one thing to have a "righteous indignation" when bad things crash and burn. But I have yet to read about an SP drug that you think is benificial and worthwhile. Can you name one? Can you name one SP drug that you are hoping will succeed?

Anonymous said...

The following is from the NJ Star Ledger on asenapine:

"Schering-Plough originally expected FDA approval to sell the drug last June. The company won't answer the FDA's new request until the end of March, according to the statement."

So the PDUFA due date was in June. Plus I just found on the internet an FDA CDER Policy and Procedure dated June 23rd allowing communication to companies if the PDUFA timeline will not be met.

So it looks like the original PDUFA due date was between June 23rd and June 30th when Fred had his WSJ interview. Maybe something happened after he gave the interview on handling adversity mid-June.

The Star Ledger's article also indicates SP will make a submission by end of March. So if it's a major resubmission (which should be) then there's a 6 month review clock with a due date at the end of Sept. Otherwise it's 2 months for labeling. Of course things could happen in less time for both of them.

Now assuming that someone was fired mid-Dec for whistleblowing these timelines could coincide with FDA finding out info from an appeal filing and discovery documents with the Merit Systems Protection Board (MSPB) and with the likely decision date by the MSPB (mid-Sept).

Condor said...

This is tantalizing, Anonymous [Cough -- Oh, Red Sock-Eyed one. . .] -- will wait for the rest.

~~~~~~~~~~~~~

Now, for Nathan -- Just one?

St. Joseph's Childrens' Aspirin:

It all began with a 16-year-old's dream. In 1908, young Abe Plough borrowed $125 from his father, purchased a horse and wagon, and created Plough, Inc., selling homemade remedies to small-town folks and farmers around Memphis, Tennessee. His plan worked, and his long career was launched with a long stream of product innovations that led him to help build the company presently known as Schering-Plough Corporation, a research-based pharmaceutical and consumer product manufacturer, with such well-known products as St. Joseph children's aspirin, Dr. Scholl's foot powder, and Maybelline cosmetics.

Throughout Mr. Plough's long career, he was known for his generosity, contributing millions to local and national organizations. He is fondly known to some as "Mr. Anonymous" because of the many anonymous gifts he gave during his lifetime. In 1960, he founded the Plough Foundation, whose focus is to provide aid to charitable organizations that benefit the greatest number of people in the City of Memphis and Shelby County. One of the city's major private philanthropies, the Foundation has supported programs for education, children, and families for many years. Although Mr. Plough died in 1984, he continues to achieve what he truly believed was success -- giving to the greatest number of people.

Mr. Plough's efforts have not gone unrecognized. Among the numerous honors and awards given to Mr. Plough were the Human Relations Award from the National Conference of Christians and Jews and the Dean's Award for contributions to the field of pharmacy from the University of Tennessee. Mr. Plough was also the first individual to ever receive an award from the U.S. Consumer Product Safety Commission for his pioneering efforts to assure safe products for children. . . .

And this:

1993 -- The United States FDA approves Betaseron®, at the time the only medication for the treatment of multiple sclerosis, specifically to treat the relapsing-remitting course of the disease. . . .


Schering-Plough, pre 1995.

Anonymous said...

Wait a second. Something is really fishy about the asenapine approvable letter.

The following is directly from the SP press release.

"Schering-Plough Corporation (NYSE: SGP) today announced that the U.S. Food and Drug Administration (FDA) has issued a complete response letter for SAPHRIS(TM) (asenapine) sublingual tablets in the acute treatment of schizophrenia in adults and in the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults as monotherapy. The action letter includes proposed labeling for both indications and a request for supplemental data from the existing asenapine database. No additional clinical trials have been requested."

OK this means that there has to be 2 adequate and well controlled trials for each indication. Now Schering has admitted in press releases previously that asenapine did not work in 2 of the 4 studies in schizophrenia. That means that the asenapine had to show efficacy in both of the other 2 studies and that they were adequate and well controlled.

Well it appears based on publicly released information that at least one of the 2 were not adequate. This is outlined by The Gerson Lehrman Group.

See http://www.glgroup.com/News/Does-The-FDA-Acceptance-of-The-NDA-for-Asenapine-Signal-A-Good-Outlook-for-Schering-Plough-(NYSE--SGP)--19717.html

It appears that one of the 2 studies being relied upon by Schering and FDA for the schizophrenia indication was published in the Journal of Clinical Psychiatry in October 2007.

First per the web posting there problems with matching the population in terms of disease severity in the risperidone control group which would make it inadequately controlled. Yet even more important was that risperidone did not work meaning it was a FAILED study

For the non-scientists out there when you do an experiment you need a negative control (placebo) which won't work, and a positive control (that presumably will work). If the placebo works or the active control doesn't work the study is uninterpretable and you thus do not have and adequate or well controlled study.

Thus it doesn’t matter whether asenapine showed a difference from placebo, when you talk about a failed study you are only talking about whether the positive control failed to work, i.e. the study failed, not the test drug asenapine. In contrast in other press releases Schering called the study where neither asenapine nor the active control worked a failed studied. While it is a failed study, Schering claims it’s failed because both the control AND asenapine failed to work. Thus it appears that Schering was intentionally trying to mislead the public as to the definition of a failed study and thus probably knew they didn't have two adequate and well controled studies for schizophrenia when they submitted the NDA.

Consequently it appears that there should not have been an approvable letter issued for the schizophrenia indication.

Salmon

Anonymous said...

Something is really fishy.

By providing labeling the FDA has admitted that this is an approvable letter and not a non-approval.

Yet the only time the Food Drug and Cosmetics Act allows an approvable letter is when only labeling negotiations are needed for approval. If additional data is requested such as the submission of new analyses as indicated by Schering for asenapine then the law requires non-approval and no labeling should have been provided by the FDA.

I would think that if the FDA had actually followed the law then a nonapproval letter would have been issued and announced in July and the stock price drop would have been even greater than occurred with the announcement of the cancer finding with the SEAS trail. Also if the PDUFA due date was actually before the end of June then the nonapproval should have been included in the quarterly report as a material fact.

In addition, an approvable letter issued now keeps the stock price higher than a non-approval letter would.

I believe that FDA is intentionally manipulating the timing and contents of the complete response letter in order to obfuscate the truth. In addition Schering should know the laws and regulations regarding this and by including the information they did in the press release it appears to me like this is an apparent attempt to obfuscate material information in order to be intentionally manipulate the stock price.

Anonymous said...

Summary.

By law (FD&CA) labeling can only be provided by FDA when application is approved or approvable.

By law (FD&CA) approvable actions are only allowed when just labeling negotiations are needed (2 month time frame).

By law (FD&CA) requests for additional information other than labeling changes REQUIRE a nonapproval letter.

Under the FDAAA 2007 labeling is only to be provided if approvable or approved.

The timing and circumstances are suspect and indicate collusion between FDA and Schering to manipulate the quarterly report and the stock price on an ongoing basis.