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Similar to Update on Recent OPDP Letters and FDA Bad 2012
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Update on Recent OPDP Letters and FDA Bad 2012
- 1. Alan Bergstrom Senior Director, Commercial Regulatory Affairs CBI 14th Annual Forum on Off-Label Guidelines October 11, 2012 Update on OPDP Letters, Off-Label Settlements, and FDA Bad Ad Program
- 2. The content, views, and opinions in this presentation are my own and do not in anyway represent the views or opinions of Daiichi Sankyo, Inc.
- 3. 3 What is Off-Label Information •HCPs can lawfully use or prescribe products for uses or indications not described in approved labeling. •FDCA and regulations prohibit a manufacturer from introducing new drugs or devices into interstate commerce for a use that FDA has not determined to be safe and effective •Statements that promote a drug or device for uses other than those approved by FDA may be used as evidence of a new use. •Introducing a product into commerce for such a new intended use would generally violate the law.
- 4. 4 Recent OPDP Letters re Off-label use •In 2010, 48 Untitled Letters or Warning Letters were issued. 3 were for unapproved uses. 2 of these were Warning Letters. •In 2011, 31 letters total, of which 3 were unapproved uses. •Through August 2012, 20 letters total, 2 for unapproved uses
- 5. 5 Recent OPDP Letters re Off-label use •Amgen 5/24/2010 - oral statements at ASHP that VECTIBIX is a first- line therapy which is an unapproved use •Forest 4/28/2011 - oral statements by a sales rep that SAVELLA is approved for fibromyalgia and useful in back pain and mood disorder •Ortho-McNeil, Janssen 8/26/2011- Oral statements at ASHP that NUCYNTA is effective in Diabetic Peripheral Neuropathic Pain •Sunovion 12/14/2011-Oral statements to an HCP about ongoing studies for use of LATUDA in bipolar disorder Oral Statements by Sales Reps
- 6. 6 Recent OPDP Letters re Off-label use •Merck 2/28/2012-oral statements by a physician speaker at promotional event suggesting SAPHRIS was safe and effective for an unapproved use Oral Statements by Speaker
- 7. 7 Recent OPDP Letters re Off-label use •Slate Pharmaceuticals WARNING Letter 3/24/2010 - website and consumer video for TESTOPEL which promoted treatments for depression, ED, T2DM, mood disorders, loss of sexual interest, and for increased muscle mass and bone strength •Novartis WARNING Letter 4/21/2010 – website which promoted Gleevec for neoadjuvant therapy prior to surgery Websites and Consumer Video
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- 13. 13 Recent OPDP Letters re Off-label use •Ferring 3/30/2012- sales aid for FIRMAGON suggests an unapproved new use as neoadjuvant use prior to radiation or to treat rising PSA levels Sales Aid
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- 15. 15 Off-Label Settlements •Ortho-McNeil Pharm. LLP and Ortho-McNeil Jansen - TOPAMAX - $81.5M •AstraZeneca LLP and AstraZeneca Pharm. LP – SEROQUEL $520M •Novartis Vaccines - TOBI $72.5M •Eisai – ZONEGRAN $11M •Allergan – BOTOX $600M •Forest - CELEXA, LEXAPRO $313M •Novartis – TRILEPTAL $185M •Kos Phar – NIASPAN, ADVICOR $51.4M •Elan Corp ZONEGRAN $214.5M •Total $2,048M 2010
- 16. 16 Off-Label Settlements •Merck – VIOXX $950M •NovoNordisk – NovoSeven $25M •Pfizer – DETROL $14.5M •Scios – NATRECOR $85M •UCB – KEPPRA $35M •Total $1,109M 2011
- 17. 17 Off-Label Settlements Total for 2010 and 2011 was $3.157 Billion
- 18. 18 Notable Off-Label Settlements •Settled for $321 million (criminal) and $628 million (civil) involving off- label promotion of VIOXX • DoJ press release announcing the settlement specifically refers to Warning Letter issued in Sept 2001 •Promotional audio conferences June 2000 in which VIOXX was promoted for unapproved uses and unapproved dosing regimens. • …effective in terms of treating patients with rheumatoid arthritis. • …safe and effective for …prevention of cancer and invasive cancer, and for the treatment • …COX-2 seems to be able to interfere with programmed cell death. Therefore you get this increased cell growth which allows polyps to form, cancer and then invasive cancer. And by blocking COX-2 you can actually prevent the development of colon polyps, cancer and invasive cancer. • …within one or two pills acute attacks of gout were being shut down. • …potential uses of these drugs, the most exciting right now I guess in two areas, one is Alzheimer’s disease… Merck 12/16/2011
- 19. 19 Notable Off-Label Settlements •Abbott – $1.5 billion for the off-label promotion of DEPAKOTE for agitation, aggression in elderly dementia patients, and schizphrenia •GSK – $3 billion for the off-label promotion of PAXIL for treating depression in patients under 18 and WELLBUTRIN for weight loss, sexual dysfunction, substance addictions and ADHD •These two settlements exceed the $3.157 billion collected in 2010 and 2011. 2012
- 20. 20 Bad Ad Program Initial kick-off May 2010 Letter to 33,000 HCPs, PR, informational video, Bad Ad brochure, exhibits at 15 medical conferences, Bad Ad webinar In the first year, received 328 reports of potentially untruthful or misleading promotions (188 from HCPs, 116 by consumers, 24 from pharma) Issued 5 letters For 2011-2012 – continued to raise awareness through CE program, case studies and Bad Ad journal ad Issued 3 letters For the future, will continue CE programs, continue liaison with healthcare organizations, and pursue additional opportunities with medical, pharmacy, and nursing schools to enhance education.
Editor's Notes
- Once a drug or medical device has been approved or cleared by FDA, generally, health care professionals can lawfully use or prescribe that product for uses or treatment indications that are not included in the product's approved labeling. The Federal Food, Drug, and Cosmetic Act (FD&C Act) and FDA's implementing regulations prohibit manufacturers and distributors (firms) from introducing new drugs, new animal drugs, and most Class III medical devices into interstate commerce for any intended use that FDA has not determined to be safe and effective. Statements that promote a drug or medical device for uses other than those approved or cleared by FDA may be used as evidence of a new intended use. Introducing a product into commerce for such a new intended use without FDA approval or clearance would, under these requirements, generally violate the law.(Guidance on Unsolicited Requests)
- Amgen VECTIBIX is indicated as single agent for EGFR expressing metastatic colorectal carcinoma with disease progression on or following fluoropyridine, oxiplaytin and irinotecan containing regimens. On Tues Dec 8, 2009, ~ 11:35 during 44th ASHP Midyear Clinical Meeting and Exhibition a rep said to a DDMAC rep (in word or substance) that VECTIBIX “is also indicated for patients who have progressed” and that liver issues and neuorpathies were not as big of an issue compared to FOLFOX or FOLFIRI suggesting that it could be used as first line therapy instead of while on or following FOLFOX or FOLFIRI. SAVELLA is approved for management of fibromyalgia. On Wed, May 12,2010, during a detail with a physician said that it is useful or back pain and mood disorder (elevates mood and relives depression). Also that it is approved for depression in EU. BAD AD Complaint NUCYNTA indicated for relief of moderate to severe acute pain. Tues, Dec 8, 2010, at ASHP DDMAC witnessed rep stating that NUCYNTA is useful in the treatment of Diabetic Peripheral Neuropathic Pain. Although the indication is broad, DPNP is a chronic pain condition that would require a specific indication. (studies were fro 72 hours or 10 days in buinionectomy or end stage degenerative joint disease LATUDA - On Tuesday, May 17, 2011, at approximately 1:40 PM, a sales representative from Sunovion made a sales call to a psychiatrist at his office. During this sales call, the sales representative indicated that Latuda is only approved for schizophrenia use, but studies for use in bipolar disorder are being done and it is only a matter of time before it is approved for bipolar disorder. The sales representative continued the discussion of the unapproved use of Latuda for bipolar disorder by pointing out that two other psychiatrists in the area are using Latuda for the treatment of bipolar disorder, and both are pleased with the results in these patients. Overall, the sales representative spent a considerable amount of time during the sales call discussing the off-label use of Latuda in the treatment of bipolar disorder. According to its PI, Latuda is only indicated for the treatment of patients with schizophrenia. Therefore, the oral statements made by the sales representative misbrand the drug by suggesting a new “intended use” for Latuda for which the PI lacks adequate directions for use.2
- SAPHRIS is indicated for the treatment of schizophrenia….. Or as monotherapy or adjunctive therapy (with lithium or valproate) for the acute treatment of manic or mixed episodes associated with bipolar I disorder. On Apr 26, 2011 a speaker physicain delivered a lunch presetnation to a group of physicians. He indicated that he prescribes SAPHRIS for the treatment of Major Depressive Disorder just as he might use ABILIFY. BAD AD Complaint
- TESTOPEL (letter issued 3/24/2010 and posted 4/16/2010) is indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone such as primary hypogonadism and hypogonadotrophic hypogonadism. Several webpages have mentioned testimonials for reclaiming life in patients with depression, erectile dysfunction, Type 2 Diabetes and HIV. Also promoted the beneifts of treatment with TESTOPEL as improved mood, increased sexual interest, restoration of erectile function, increased muscle mass, and increased strength of bones. GLEEVEC (letter posted 5/4 but issued 4/21/2010) is indicated (among others) as adjuvant therapy of adult patients following complete gross resection of Kit (CD117) positive gastrointestinal stromal tumors (GIST). The professional and consumer portions of the website promote GLEEVEC for neoadjuvant use before surgical resection of GIST tumors. Although the webpages did not explicitly use the tradename GLEEVEC, the footnotes on the pages clearly indicated the established name for GLEEVEC and the text mentioned the NCCN Treatment Guidelines for GIST which exclusively recommend the use of GLEEVEC for neoadjuvant therapy. Therefore the webpages suggest a new, unapproved use for GLEEVEC for which safety and effectiveness have not been established. There is no safety and efficacy information regarding use of Gleevec before surgery.
- Here is the page with claims of benefit of Testopel therapy Improved mood Increased sexual interst Restoratin of erectile function Increased muscle mass Increased strength of bone
- Example page for a future video of a patient with depression talking about how Testopel helped him to reclaim his life. Similar pages for for pateint testomonial video for erectile dysfunction, type 2 diabetes, HIV
- FIRMAGON is a GnRH antagonist indicated for the treatment of patients with advanced prostrate cancer. USE FIRMAGON FIRST, USE FIRMAGON FIRST IN 3 PATIENT TYPES (#1 planning hormone therapy prior to radiation and #2 considering hormone treatment due to rising PSA levels FIRMAGON is not indicated as neoadjuvant therapy or for rising PSA levels. It is approved for advanced prostrate cancer. While FIRMAGON’s indication is a general one, pivotal trials specifically excluded recruiting patients indicated for neoadjuvant hormonal therapy and those receiving neoadjuvant hormonal therapies.
- TOPAMAX approved as an anti-epileptic drugn for the tx of partial seizures but not for any psychiatric use. Doctor for a day program, join with reps in details, speaker meetings and dinners to promote for psychiatric uses. Whistle blower SEROQUEL originally aprpoved in 1997 for tx of manifestations of psychotic disorders, narrowed in 2000 to tx o short term tx of schizophrenia only, in 2004 approved for short term tx of manic episodes associated with bipolar disoprder. In 2006 approved for bipolar depression. Promoted for agression, alzheimer’s, anger management, anxiety, ADHD, dementia, depression, moeed disorder, PTSD, and sleeplessness. Targeted to docs wgho typically do not treat schizophrenia or bipolar disorder such as geriatricians, PCPs, pediatricians, and long term care facilities. Whistleblower Also Letter Dec 2008 to AZ for sales rep statements regarding use of Seroquel for Major Depressive Disorder. Physician requested more information and received a mailing about 8 trials in MDD which was not the result of an unsolicted reqeust. Novartis Vaccines TOBI approved for tx of certain cystic fibrosis patients. Promoted off-label for other diseases and for cystic fibrosis patients who did not meet the limitations in the Pi and for whom TOBI was not a medically accepted tx. Whistleblower ZONEGRAN – Approved for tx of partial epileptic seizures in adults. Both Elan and Eisai promoted for modd stabilizaton, migraine, chronic daily headaches, eating disorders, obesity, weight loss, and siezure sin children under 16. Whistleblower Allergan BOTOX Among other indicatinos is approved for cervical dystonia (involuntary neck muscle contraction). Promoted fro pain and headache through a promotional campaign which stated that cervical dystonia was underdiagnosed and that doctors could diagnose CD based on headache and pain symptoms. Also trained doctors and how to obtain reimbursement for this off-label use. Whislteblowers Forest CELEXA and LEXAPRO approved at the time for the tx of adult depression. Activities included directing sales reps to promote to physicians who treated children and adolescents. And hiring speakers to talk to pediatric specialists. It was only later that Lexapro was approved for MDD in adolescents 12-17. Whislteblower Novartis TRLIPEPTAl
- Not included in this is the recent settlement by J&J for off-label promotion of Risperdal to the tune of up to 2 billion.
- Comprehensive reviews – meaning a strong level of knowledge about misleading promotion 87/188, 24/116, and 14/24 respectively. So 125 of the 328 reports were of high enough quality to trigger an investigation For 2010-2011 issued 5 letters - the letter to Forest previously discussed was a Bad Ad Complaint For 2011-2012 issued 3 letters - the letter to Merck previously discussed was a Bad Ad Complaint Initial kick-off May 2010 Letter to 33,000 HCPs, PR, informational video, Bad Ad brochure, exhibits at 15 medical conferences, Bad Ad webinar In the first year, received 328 reports of potentially untruthful or misleading promotions (188 from HCPs, 116 by consumers, 24 from pharma) Issued 5 letters - the letter to Forest previously discussed was a Bad Ad Complaint For 2011-2012 – continued to raise awareness through CE program, case studies and Bad Ad journal ad Issued 3 letters - the letter to Merck previously discussed was a Bad Ad Complaint For the future, continue CE programs, continue liaison with healthcare organizations, and pursue additional opportunities with medical, pharmacy, and nursing schools to enhance education.