Paging Salmon -- for additional color, and perspective, here -- but Greg Miller, writing at GeigerCount.com, certainly has the broad outlines correct, based on what I'd known to date about Schering-Plough to New Merck's Saphris®/Sycrest® (asenapine):
. . . .[Pfizer's now ex-R&D head] LaMattina was also wrong with asenapine. Pfizer’s decision to withdraw from the development of asenapine sparked interest with Fred Hassan, Schering-Plough’s chief executive. On March 11, 2007, Schering-Plough bought Organon, known for its birth control pills, for $14.4 billion. In August 2009, at a time when Schering-Plough was in the process of being integrated into Merck, the FDA approved asenapine tablets for the treatment of schizophrenia and bipolar disorder.
Merck launched the drug under the brand name Saphris and marketed it as a maintenance treatment of schizophrenia, a chronic, severe and disabling brain disorder and as adjunctive therapy to lithium or with valproate for bipolar 1 disorder. The FDA had also issued a black box warning saying that elderly patients with dementia-related psychosis should not use Saphris.Results showed that this patient population when treated with Saphris had twice the risk of death than those treated with placebo. The most common cause of death was found to be related either to cardiovascular or infectious causes. In September 2010 a sublingual formulation of asenapine was approved by the FDA as well as by European authorities. This enabled the first market introduction in Europe, where the drug was called Sycrest and indicated for the treatment of moderate to severe manic episodes associated with bipolar 1 disorder. . . .
I would counter that, given the market's actual reaction to Saphris -- arguably, here in the states, and certainly in Europe, Pfizer's LaMattina was. . . right. What did "Fast Fred" Hassan spend on asenapine? Perhaps $750 million to $1 billion -- all in(?). And it isn't even generating $100 million in worldwide annual sales, even a full year on. And that's before we talk about the inappropriate use of the drug, at state-funded mental hospitals, as a chemical restraint.
Paging Salmon. . . . STAT!
3 comments:
I would disagree about your assessment that Greg Miller has the broad outlines on Saprhis/Sycrest being correct.
Let me illustrate with Mr. Miller's own statements.
Miller - “On Monday, November 27 (2006)… Pfizer announced that it withdrew from collaborating with Organon in a development program for asenapine, an experimental drug for the treatment of schizophrenia and acute mania associated with bipolar 1 disorder. The decision came after Pfizer scientists began to review results from an interim analysis of a phase 3 trial with schizophrenia patients in October.”
Wrong - the phase III studies in schizophrenia had concluded and this was the final analysis not an interim analysis.
Miller - “Pfizer scientists were afraid that the results might not be sufficient for a 2007 NDA filing with the FDA and lowered their earlier commercial expectation for asenapine accordingly.”
Correct – if you look at the data in the FDA reviews the phase II study failed, 2 phase III studies were negative, and the third phase III study was equivocable with the 5 mg dose showing efficacy and the 10 mg dose not showing efficacy.
In total,it’s likely Pfizer thought that they needed to do at least 1 more study and possibly more to get a second positive study to meet the legal requirements for approval. Doing so would likely delay filing for at least 2 years (2009 with the best case for approval being 2010) after Risperidal had gone off patent (2008) and becoming uncomfortably close to when Zyprexa would go off patent (2011). This also does not take into account their thoughts on what they were seeing in the safety database at that point,
Miller - “Concurrently with Pfizer’s announcement, Toon Wilderbeek, Organon’s president and a board member of Akzo Nobel, a Dutch company that fully owned Organon said that they would assess whether further trials might still be required in order to be able to submit a strong NDA file.”
Correct – this is simply a less noticable way of saying what I said above.
(Continued.)
Miller - “In August (13th) 2009, at a time when Schering-Plough was in the process of being integrated into Merck, the FDA approved asenapine tablets for the treatment of schizophrenia and bipolar disorder. Merck launched the drug under the brand name Saphris and marketed it as a maintenance treatment of schizophrenia, a chronic, severe and disabling brain disorder and as adjunctive therapy to lithium or with valproate for bipolar 1 disorder.”
Wrong. It was not initially approved for maintenance treatment it was for the treatment of acute psychotic attacks (6 weeks only). It wasn’t approved for maintenance therapy until a year later on Sept 3rd, 2010.
Wrong again. It was not approved as adjunctive therapy in bipolar disorder. It was approved as monotherapy in acute manic attacks.
Miller - “The FDA had also issued a black box warning saying that elderly patients with dementia-related psychosis should not use Saphris. Results showed that this patient population when treated with Saphris had twice the risk of death than those treated with placebo.”
Wrong. Although Saphris has a black box warning regarding use in dementia related psychosis this is class labeling and is due to deaths observed in this population with off-label use of other antipsychotics. These labeling changes were communicated to JNJ for Rispredal on August 17, 2005, for Supplement No. 42 with the FDA’s letter to JNJ stating “These “Changes Being Effected” supplemental new drug applications provide for revised labeling regarding mortality in elderly patients with dementia-related psychosis.
We completed our review of these supplemental new drug applications and they are approved, effective on the date of this letter, for use as recommended in the final printed labeling (FPL) submitted on April 29, 2005 (attached).
Changes to the Zyprexa labeling was approved on February 16, 2006 with the FDA letter to Lilly stating The May 9, 2005 Supplement (No. 032) “Changes Being Effected” supplemental new drug applications provide for a Boxed Warning and Bolded Warning section of the labeling concerning increased mortality in elderly patients with dementia-related psychosis.
Miller - “In September 2010 a sublingual formulation of asenapine was approved by the FDA as well as by European authorities.”
Wrong. The initial US approval was Aug 13, 2009 and the EU approval was Sept 22, 2010. Doesn’t this guy even read what he wrote elsewhere in his article.
Finally I noticed the GeigerCountReport website states:
“We follow the paper trail of biotech and pharma companies, and put the facts in context.”
Yeah riiiiiiight.
I think Pfizer got it right and Freddie and with some shenanigans at the FDA simply put some lipstick on a pig and sold Saphris to the first sucker he could find.
Salmon
Fabulous, Salmon -- THANKS!
This will be a new post for all the Sunday morning coffee sippers -- okay?
Nice work!
I knew you'd likely happen by. . .
Namaste
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