An important new article in the New England Journal of Medicine takes a critical look at pharmaceutical companies for their Direct-to-Consumer (’DTC’) advertising of drugs. The piece by Dr. Miriam Schuchman, “Drug Risks and Free Speech — Can Congress Ban Consumer Drug Ads,” offers a fresh perspective on drug safety risks.

This is particularly important at a time when Vioxx was withdrawn from the market for being associated with coronary safety risks, followed by the recent NEJM report and FDA announcement that diabetics using Avandia had a 43-percent greater risks of heart attack risks than those not taking the GlaxoSmithKline drug.
What does this mean for Pfizer’s Exubera? Dr. Shuchman raises a point that this blog has reported on for over a year: that the FDA granted approval to put the inhaled insulin on the market, “despite the fact that safety studies are still under way.” She is a national correspondent for the NEJM.
Does this show greater caution at the FDA, or drug approvals as usual? It would not.

Take the example of Zelnorm, a drug that, until recently, was used to treat women with irritable bowel syndrome (’IBS’).
Dr. Schuchman says that Zelnorm sales benefited from DTC exposure while it was on the market for four (4) years. That was, until “the FDA withdrew it this past March because it didn’t consider the drug’s benefits sufficient to justify exposing patients to even low risks of a cardiac event.”

But Shuchman reports that “although the drug was only 5 to 10% more effective than placebo for women and was not shown to work at all for men, the belly-baring ad seems to have worked wonders: U.S. doctors wrote 2.1 million prescriptions for Zelnorm in 2005.”

That raises even more questions about Exubera when Pfizer launches DTC ads for the drug this summer. Despite poor Exubera sales, the advertising campaign could be a shot in the arm for Pfizer. Whether the drug will have adverse long-term effects on diabetics’ safety, however, is still an open question.

The latest issue of BusinessWeek has an article on Exubera that, if accurate, may not bode well for Pfizer’s hope that it’s new inhaled insulin will be a blockbuster drug.

It cites “mounting resistance from patients and physicians” to using the diabetes drug as one reason why some Wall Street analysts remain skeptical of Pfizer’s prediction that Exubera’s could bring $2 billion in annual sales for the drug company.

Real insiight comes from the magazine’s interview with a 57-year-old insulin-dependent Type 1 diabetic, Janet Ruhl:

She thinks Exubera will be hard to use and could cause lung damage. “It looks like a terrible idea,” Ruhl says.

It’s a good idea that the spoke with an insulin-dependent diabetic. Part of Pfizer’s marketing campaign has been to try and scare folks into thinking that diabetics should be afraid of injections. If insulin dependent diabetics and their doctors are already skeptical about the drug’s safety, that’s a problem for Pfizer.

As this blog first observed over 3 months ago, that’s what Pfizer’s “Breeze Study” did when trying to recruit diabetics for an Exubera safety study by using loaded language suggesting that diabetics should fear injectable insulin over Pfizer’s inhaled insulin — a drug that Pfizer and the FDA already know has certain safety risks.

The BusinessWeek article also highlighted the potential liabilities (e.g., pulmonary risks) and safety risks of the drug — something this blog has been following closely for the last 6 months.

Could Exubera turn out to be a bigger safety risk for some diabetics than is already known? That sounds like a bit too much like Vioxx dangers and product liability litigation down the road. If that happened, what a nightmare for diabetics and their healthcare practioners that would be.

Is marketing Pfizer’s new inhaled insulin as being just as good as injectable insulin a Pfizer marketing ploy, even if there may not be proof of such an effect on diabetics? Does the company want to sell billions of dollars worth of the new drug? These are obvious question diabetics should be asking themselves if they’re even considering trying the new inhaled insulin from Pfizer and Nektar Therapeutics when it hits the market in July 2006.

As Exubera-Risks.com observed yesterday, the U.K.’s healthcare watchdog NICE found that Pfizer’s submissions to the agency in favor of winning approval for coverage by Britain’s National Health Service were “positively misleading, and biased in favour of inhaled insulin,” and that the “most misleading bit in Pfizer’s materials” was that they purported to show that Exubera gave diabetics “better blood sugar control” when, in fact, “the [inhaled insulin drug] trials showed no difference.” According to NICE, the research just wasn’t there to support Pfizer’s position.
This is not the first time that marketing efforts appear to have been used to try to convince diabetics and health care providers to use Pfizer’s new FDA-approved drug that insulin shots can be scary, horrific, or bad. Is playing on patients real, or newly-imagined fears, an effective inhaled insulin marketing strategy?  It’s too early to know the answer, since Exubera has not yet hit the market.

However, it seems much like the strategy used to recruit patients to participate in the Exubera “Breeze Study” mandated by the FDA.  The FDA, as a pre-condition of Exubera approval, directed Pfizer to conduct a series long-term safety studies for pulmonary risks, use by children (currently prohibited) and other safety risks for diabetics using Exubera inhaled insulin over an extended period of time (5 - 7 years).

It comes as no surprise that Pfizer’s new Exubera inhaled insulin marketing campaign at the American Diabetes Association’s 2006 Scientific Sessions highlights safety concerns and potential drug risks.

Pfizer’s press release starts off by highlighting what it calls

New Long-term Safety and Efficacy Data:

Two studies assessed the long-term safety and efficacy of Exubera in patients with type 1 and type 2 diabetes. In these Phase III studies, the level of sustained blood sugar control in patients taking Exubera was compared to patients taking placebo. A similar comparison was made regarding respective differences in weight gain. (Saturday, June 10, 10:15-12:15, Washington Convention Center, Room 146 (Oral presentations 109, 110))

Misleading, however, is what Pfizer wants physicians, diabetics, and diabetes health  care professionals to believe is the defintion of a ‘long-term’ study of the drug’s safety.  It’s not a five (5) or ten (10)-year period. It’s just two (2) years.

That’s a serious sematic difference. Especially when the FDA conditioned its approval of Exubera on Pfizer’s commitment to undertake and report on long-term safety studies of Exubera even after the inhaled insulin is put on the market.

At the ADA, Pfizer is showcasing the following Exubera ‘long-term’ safety studies for Type 1 and Type 2 diabetics:

• Inhaled Human Insulin (Exubera®) Therapy Shows Sustained Efficacy and Is Well Tolerated over a 2-Year Period in Patients with Type 2 Diabetes (T2DM)
  
  
• Inhaled Human Insulin (Exubera®) Therapy Shows Sustained Efficacy and Is Well Tolerated over a 2-Year Period in Patients with Type 1 Diabetes (T1DM)

The FDA is requiring Pfizer, however, to conduct real long-term safety studies of at least 5 years.

Let’s wait and see how Pfizer spins this discrepancy at the ADA meeting.

According to the Washington Post, Congress’s investigative agency will release a new report today that is highly critical of the U.S. Food and Drug Administration (’FDA’) for lacking “clear policies for addressing drug safety issues.” Today’s Wall Street Journal highlights the report’s conclusion that the FDA “lacks a clear and effective process for making decisions about, and providing management oversight of” drug safety following a medication’s FDA approval.

The report from the Governmental Accountability Office (’GAO’) was launched after the Vioxx safety debacle in 2004, when Merck pulled the prescription pain relief drug from the market after an increased risk for heart attacks and strokes was found for users of the chronic pain-relieveing drug.
What will this mean for Type I or Type II diabetics who start to use Exubera, Pfizer’s new FDA-approved inhaled insulin? Potentially, quite a lot.
The FDA’s January 27, 2006 approval of Exubera directed Pfizer to conduct a long-term study of 5,000 patients using the new inhaled insulin.  This request reportedly stems from a concern that no sufficiently long-term safety data exists for the drug that could affect a patient’s pulmonary function.  The drug was approved with a list of FDA warnings, including that diabetics who smoke and others at risk for impaired or decreased lung function cannot us the drug.  Signficantly, the FDA did not approve Exubera for use by children with diabetes drug, given safety concerns.

Recently, Exubera-Risks reported what it learned about the Breeze Study seeking to recruit Type II diabetics to participate in a 26-week study for:

“men and women ages 18-80 years old with Type 2 Diabetes to participate in an approximately 26 week research study which will assess the safety and effects of investigational inhaled insulin (Exubera®) on your blood sugar control if you are already taking 2 or more oral medications.”

Will a 26-week study be sufficiently long to assess the drug’s long-term safety? That is a question one wonders whether the FDA and Pfizer have asked and answered.