By Martha Rosenberg, Contributor | March 13, 2016
Last Updated: March 14, 2016 2:20 pm
Asthma is big business for Big Pharma. Advair was the third bestselling drug in the world in 2013 and the asthma drugs Singulair and Symbicort were also blockbusters. So it is no surprise the prospect of a high-tech injectable drug that stops an allergic response by binding to Immunoglobulin E (IgE) made Big Pharma sit up and take notice.
Xolair (omalizumab), developed from humanized rodent cells (yes, you read that right), is part of Big Pharma’s new wave of bio-engineered liquid drugs, rolled out when blockbusters like Lipitor and Viagra went off patent. Injected drugs/biologics can earn $20,000 or more per patient per year and are resistant to the quick generic competition that threatens easier-to-replicate pills. Currently biologics Humira and Enbrel are bestselling drugs.
Novartis and Genentech, which decided to co-market Xolair, sought FDA approval for four conditions in 2001—pediatric and adult asthma, and pediatric and adult seasonal allergic rhinitis symptoms (SARS). But the FDA only approved Xolair to treat one, in 2013— “moderate to severe persistent asthma” in patients over 12 whose symptoms are “not adequately controlled on inhaled corticosteroids” and who have a positive skin test or reactivity to an allergen.
The limited number of patients who could be prescribed Xolair under this approval was a big disappointment. But so was the reason for the restricted indication: in clinical trials, the FDA had detected signs of early stage malignancies! The FDA also detected many anaphylactic responses (life threatening allergic responses) which earned Xolair a black box warning. Years later, Xolair was also linked to a higher risk of heart attack, mini-stroke, chest pain, and blood clots.
Unsavory Sales Schemes Charged
How do you sell a drug too dangerous for children and too dangerous for seasonal allergic rhinitis symptoms that costs up to $24,000 a year? A drug that can only be used after corticosteroids have failed and a IgE serum test has been conducted? A drug so linked to anaphylaxis it can only be administered in a medical setting where patients have to remain for two hours of observation? (Amounting to four to eight hours of doctor and patient time a month, since the drug is given every two or four weeks.)
How do you sell a drug too dangerous for children and too dangerous for seasonal allergic rhinitis symptoms that costs up to $24,000 a year?
By breaking the law, according to whistleblowers who sold Xolair at Novartis and Genentech—allegedly with a scheme of kickbacks and bribes, misinformation about Xolair’s approved uses, and risks and insurance fraud.
Novartis, Genentech, and Roche (which acquired Genentech in 2009) “determined as early as 2003 that they would never succeed in transforming Xolair into a blockbuster or near-blockbuster drug unless they broke the law,” say their complaints. “And that is exactly what they have knowingly done, by aggressively and illegally marketing Xolair, on a national basis, to induce HCPs [health care providers] to prescribe Xolair for wide-ranging use—despite the drug’s very limited efficacy and proven threats to patient safety.”
According to complaints, doctors and medical staff who could boost Xolair prescriptions received American Express travelers checks, expensive tickets to sports and entertainment events, opulent meals, and even trips to the Bahamas. Often payments were disguised to look medically-related, such as payments for bogus studies and to “advisory board” members, trips to “speaker” programs at fancy country clubs and casinos, unrestricted grants and honoraria of $1,000 to $3,000 that denoted no work.
Doctors and medical staff who could boost Xolair prescriptions received American Express travelers checks.
Because Xolair can cost up to $24,000 a year and doctors have to sign a SMN (Statement of Medical Necessity) to assure private and government reimbursement, sales reps “instructed and nudged” office staff to submit Xolair claims “at improper rates.” Reps were ordered to work medical settings in poor neighborhoods where patients were more likely to be on Medicaid, say complaints.
Reps also conducted off-label marketing—disregarding approved FDA uses and identified risks. They were told to use the made-up term “active asthma” when calling on doctors instead of “moderate to severe persistent asthma,” which would have limited sales. They were also told to assure doctors a two-hour wait to monitor for anaphylaxis was unnecessary and that patients in some cases could self-administer Xolair at home.
And, in blatant disregard of Xolair’s indications and safety profile, reps were even told to call on pediatricians and claim that Xolair was safe for children under 12, according to whistleblowers.
No ‘Day in Court’ for Whistleblowers Yet
Many, perhaps most, pharma companies have settled cases pertaining to bribes, kickbacks, and off-label marketing. Pfizer, GlaxoSmithKline, Johnson & Johnson, Bristol-Myers Squibb, Eli Lilly, and Victory Pharma have settled cases in recent years.
In blatant disregard of Xolair’s safety profile, reps were told to claim that Xolair was safe for children under 12, according to whistleblowers.
Yet, despite an 11-year legal journey which included deposing Novartis and Genentech reps and even “wiring” one to collect evidence, whistleblower complaints have gone nowhere. Judge William Young of Boston tossed out the main complaint a year ago claiming that “fraud was probable” but an appeal is going nowhere fast.
Some suggest the reason is Genentech is increasingly enmeshed with government.
A sign in front of the headquarters of Biotech firm Genentech in South San Francisco, Calif., on July 14, 2008. (Justin Sullivan/Getty Images)
Robert Califf, M.D., the newly appointed FDA Commissioner, served as “director, officer, partner, employee, advisor, consultant, or trustee” for Genentech, according to Medscape—a fact that has disappeared from both the Medscape and Genentech sites. And in 2013, Google created Calico, a research and development company run by the chairman and former CEO of Genentech. Since then, Google life-sciences ventures have lured away Thomas R. Insel, director of the National Institute of Mental Health—a move that shocked many.
Whistleblower complaints have gone nowhere.
As whistleblower complaints about Xolair sales tactics go nowhere, there is clear evidence of patient harm. A 2011 government Pediatric Postmarketing Adverse Event Review found “81 serious pediatric reports” and five deaths in children 0–16. Another study found “20 infants had congenital anomalies confirmed,” when their mothers were exposed to Xolair while pregnant.