Astrazeneca and Seroquel Escape Lawsuits

Back in April 2010, Astrazeneca settled the federal investigation into its marketing practices for Seroquel for a mere $520 million. I say "mere" because Seroquel alone brings in this much revenue to AZN in a few weeks. They made almost $5 billion on the drug last year. The settlement is barely dissuasive in the financial sense. We all know if you can get your product used in off-label areas where you can be the first atypical used, then your foothold will be strong and marketing costs will stay low. If you happen to get the indication later, then that's just icing on the cake (See Seroquel in Bipolar and Depression and Austism).

Now, Astrazeneca is settling its lawsuits with individuals. Yesterday they announced that 17,500 of the suits had been settled for only $198 million. I don't know which firm AZN retains, but those suits earned every penny. $198 million barely registers. Probably 2 weeks of Seroquel sales. This is all great news for AZN as they work to put the bad press behind them. There are many lawsuits left, which is good because there isn't much time left for Seroquel which goes off-patent in March 2012 if AZN can fend off Teva for that long. That's plenty of time to transition physicians and patients to XR though which currently has a patent through 2017.

Astrazeneca's Seroquel Bipolar Depression DTC TV Ad Hits the Airwaves

For a multi-billion dollar drug with an opportunity to have patient-driven prescriptions, it's surprising that it's taken this long for Astrazeneca to finally get around to a DTC TV campaign for Seroquel XR. Given that the ad is so depression-focused I wonder if the marketing team at AZ had been making this ad for the depression indication for which they're still waiting on FDA approval. If you mute the ad and just look at it, it could easily be an ad for any of the products currently advertising for major depression. I wonder if they just got tired of waiting on the approval and had the ad agency change the voiceover to accomodate the comparable indication that they do have in bipolar depression. Just an outsider's guess.

The ad itself is pretty depressing. I know the Abilify ads were criticized for being too "sunny" in their conclusions, but geez this ad could use a little. If I wasn't depressed before viewing it, I sure am now. The fair balance is rough too. All 53 seconds of it. It's always hard to hear the drug you're taking has an increased risk of DEATH.

The one thing this ad will accomplish if it doesn't get lost in the other 85 seconds is that some patients can take just 1 pill. It's the last thing we hear before the fair balance kicks in. This of course is basically the only advantage of Seroquel XR over it's soon-to-be-generic parent Seroquel. However, the suggestion is erroneous. Patients suffering from Bipolar disorder rarely can take a single medication to control their systems, esp. given the associated comorbidities to manage as well as the drugs to counter act the side effects of Seroquel. Still, the 1 pill promise could drive patients to talk to their doctor about Seroquel which is the first step in this ad paying off for AZ. It will be interesting to see if their print campaign is revised to coincide with the TV spot as well as whether AZ will seek better ad spot availability by creating a 60 second version.

FDA gives Astrazeneca a Little Slap for Off-Label Promotion

Shame on Astrazeneca for getting ahead of itself and promoting an off-label use of Seroquel. Naughty, naughty. Yes, I know that Seroquel is probably the atypical antipsychotic most used in depression, probably even more than Abilify (which has an indication in adjunctive use AND the DTC campaign to back it up). Perhaps this sales rep is among the list of upcoming layoffs...

Here's the FDA letter for those who care to get the whole dirt.

TRANSMITTED BY FACSIMILE James L. Gaskill, Pharm.D. Director, Promotional Regulatory Affairs AstraZeneca LP 1800 Concord Pike, P.O. Box 8355 Wilmington, DE 19803-8355
RE: NDA # 20-639, 22-047
Seroquel (quetiapine fumarate) Tablets Seroquel XRTM (quetiapine fumarate) Extended Release Tablets MACMIS ID #16370

Dear Dr. Gaskill:
The Division of Drug Marketing, Advertising, and Communications (DDMAC) of the U.S. Food and Drug Administration (FDA) has become aware of oral statements made by an AstraZeneca LP (AZ) sales representative on January 3, 2008, to a healthcare professional, and a mailing from AZ dated January 4, 2008, to the same healthcare provider, regarding its drugs, Seroquel (quetiapine fumarate) tablets (Seroquel) and Seroquel XRTM (quetiapine fumarate) Extended Release Tablets (Seroquel XR). The representative and the mailing recommended or suggested a use for Seroquel and Seroquel XR that has not been approved by FDA, and thus created a new "intended use" for Seroquel and Seroquel XR for which the products lack adequate directions. Thus, these promotional activities and materials misbrand the drugs in violation of the Federal Food, Drug, and Cosmetic Act (Act), 21 U.S.C. 352(f)(1), and FDA implementing regulations. 21 CFR 201.1 00(c)(1) & 201.128.

Background According to the Indications and Usage section of its FDA-approved product labeling (PI),1 Seroquel is indicated, among other things, for the following:

Bipolar Disorder
SEROQUEL is indicated for the treatment of both: • depressive episodes associated with bipolar disorder • acute manic episodes associated with bipolar I disorder as either monotherapy or adjunct therapy to lithium or divalproex. The efficacy of SEROQUEL was established in two identical8-week randomized, placebo-controlled double-blind clinical studies that included either bipolar i or II patients. Effectiveness has not been systematically evaluated in clinical trials for more than 8 weeks. The efficacy of SEROQUEL in acute bipolar mania was established in two 12-week monotherapy trials and one 3-week adjunct therapy trial of bipolar I patients initially hospitalized for up to 7 days for acute mania. Effectiveness has not been systematically evaluated in clinical trials for more than 12 weeks in monotherapy. The efficacy of SEROQUEL as adjunct maintenance therapy to lithium or divalproex was established in 2 identical randomized placebo-controlled double-blind studies in patients with Bipolar i Disorder. The physician who elects to use SEROQUEL for extended periods in Bipolar Disorder should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

Schizophrenia
SEROQUEL is indicated for the treatment of schizophrenia.
The efficacy of SEROQUEL in schizophrenia was established in short-term (6-week) controlled trials of schizophrenic inpatients. The effectiveness of SEROQUEL in long-term use, that is, for more than 6 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use SEROQUEL for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.
According to the Indications and Usage section of the FDA-approved Pi2 for Seroquel XR:
SEROQUEL XR is indicated for the treatment of schizophrenia.
The efficacy of SEROQUEL XR in schizophrenia was established in part, on the basis of extrapolation from the established effectiveness of SEROQUEL. In addition, the efficacy of SEROQUEL XR was demonstrated in 1 short-term (6-week) controlled trial of schizophrenic inpatients and outpatients.
The effectiveness of SEROQUEL XR in long-term use, that is, for more than 6 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use SEROQUEL XR for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.
Promotion of Unapproved Use

On Thursday, January 3,2008, at approximately 3:00 p.m., a sales representative from AZ in the - bt4)-made an unsolicited sales call to a physician at his office. The representative stated that Seroquel was approved for treatment of major depressive disorder (MDD). This representation was not made in response to a request for such information by the physician. As a result of this representation, the physician requested that AZ provide written information to support the claim that Seroquel has been approved for the treatment of MDD. In response to this request, AZ sent the physician a mailing dated January 4, 2008. The mailing contained information about Seroquel and Seroquel XR's use for MDD, and included summaries of eight clinical trials with referenced citations. This mailng was not the result of an unsolicited request by the physician, but rather was prompted by the sales representative's statements.
According to their Pis, Seroquel and Seroquel XR are not FDA-approved for the treatment of MDD.3 Therefore, the oral statements made by the sales representative and the information provided in the January 4, 2008, mailng, misleadingly suggest a new "intended use" for Seroquel and Seroquel XR. Because the Pis for Seroquel and Seroquel XR lack adequate directions for this use, the drugs are therefore misbranded. Although the letter to the physician states that "(AZ) does not recommend the use of SEROQUEL or SEROQUEL XR in any other manner than as described in the enclosed prescribing information," this disclaimer is insufficient to mitigate the promotion of a new "intended use" for which the products lack adequate directions.
Conclusion and Requested Action
The oral statements made and information provided by AZ and its representative recommend or suggest a use for Seroquel and Seroquel XR that has not been approved by FDA, and thus misbrand Seroquel and Seroquel XR in violation of the Act, 21 U.S.C. 352(f)(1), and FDA implementing regulations. 21 CFR 201.1 00(c)(1) & 201.128.
DDMAC requests that AZ immediately cease the dissemination of violative promotional materials for Seroquel and Seroquel XR such as those described above. Please submit a written response to this letter on or before December 15, 2008, stating whether you intend to comply with this request, listing all promotional materials (with the 2253 submission date) in use for Seroquel and Seroquel XR as of the date of this letter, identifying which of these materials contain violations such as those described above, and explaining your plan for discontinuing use of such violative materials. Please direct your response to me at the Food and Drug Administration, Center for Drug Evaluation and Research, Division of Drug Marketing, Advertising, and Communications, 5901-B Ammendale Road, Beltsville, MD 20705-1266, facsimile at 301-847-8444. In all future correspondence regarding this matter, please refer to MACMIS #16370 in addition to the NDA number. We remind you that only written communications are considered officiaL.
The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibilty to ensure that your promotional materials for Seroquel and Seroquel XR comply with each applicable requirement of the Act and FDA implementing regulations.
Sincerely, {See appended electronic signature page} Amy Toscano, Pharm.D., CPA Regulatory Review Officer Division of Drug Marketing, Advertising, and Communications
1 At the time of this violative action, the approved Pi (and the version referred to within this letter) for Seroquel was the version dated July 30,2007. Although not relevant to the issues cited in this letter, the most recent version of the Seroquel PI was approved on May 13, 2008. 2 At the time of this violative action, the approved Pi (and the version referred to within this letter) for Seroquel XR was the version dated May 17, 2007. Although not relevant to the issues cited in this letter, the most recent version of the Seroquel XR Pi was approved on October 8, 2008. 3 Seroquel is approved for the treatment of depressive episodes associated with bipolar disorder, which is a disease state that is distinct from MDD. On October 8, 2008, Seroquel XR was also approved for the treatment of depressive episodes associated with bipolar disorder.
This is a representation of an electronic record that was signed electronically andthis page is the manifestation of the electronic signature. /s/ Amy Toscano 12/1/2008 03: 13: 05 PM

Astrazeneca Saves Seroquel

Astrazeneca got incredibly great news today from a NJ court that Novartis and Teva will not be able to pursue their desired genericization of Seroquel. This stands in stark contrast to yesterday's post on Risperdal which just went generic. This is good news for all the branded atypicals as now there is just risperidone as the sole generic. Had Seroquel gone generic it would've turned the atypical market upside down. Seroquel and Seroquel XR as branded products make up over a 30% share of all atypical antipsychotics as it is and with juggernaut new indications coming in Major Depressive Disorder and Generalized Anxiety Disorder, it's not going to get any smaller anytime soon. Had it gone generic, it's likely that Abilify and Geodon would have been particularly hard hit so I'm sure their respective marketing teams are exhaling a sigh of relief.

Astrazeneca's Major Depressive Disorder (MDD) filing for Seroquel on 2/29

Well, this answers the burning question of how many licks it takes to get to the Tootsie Roll center of a Tootsie Pop. The answer varies widely. Oops that's a different question. I meant how many filings does it take for Seroquel to get an MDD indication? 7? Well, maybe. Let's see we've got 4 for monotherapy, 2 for adjuctive therapy to ongoing anti-depressant therapy (like Abilify), and 1 more for maintenance. That's quite a shotgun effect. How exactly to you plan positioning for a product in MDD with this many possible outcomes?

The answer is it doesn't matter. Because regardless of the indication you still have to deal with the sedative, weight, and metabolic issues attached to your product and the class.

I wonder how many they'll bring for Generalized Anxiety Disorder (GAD) in the next couple of months. Should be interesting...

Atypical Anti-psychotic Monopoly

Perhaps it's more of a quintopoly. Since Abilify's launch in late 2002, Astrazeneca, Jansen, Eli Lilly, BMS/Otsuka, and Pfizer have had free reign over the atypical anti-psychotic market. Starting with schizophrenia but gradually expanding to bipolar disorder, autism, major depression, and generalized anxiety disorder coming soon, these products are infiltrating every corner of the mental health market in all age groups. I don't have a lot to say here, just that's interesting how the increasingly more restrictive FDA is crushing potential competition through its tenor. bifeprunox is dead. asenapine is alive and may actually get the bipolar mania label. And, Fiapta (iloperidone) is crippled by its patent life, lack of sales force, and second-line at best status in schizophrenia.

Damn it must feel good to be one of the big five.