Healthy Skepticism Library item: 11801

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Publication type: news

Johnson A.
Insulin Flop Costs Pfizer $2.8 Billion
The Wall Street Journal 2007 Oct 19A1
http://online.wsj.com/public/article/SB119269071993163273.html?mod=blog

Full text:

Pfizer Inc.‘s decision to shelve a novel insulin inhaler and take a $2.8 billion pretax hit on the product — one of the drug industry’s costliest failures ever — rids the company of an albatross. But it suggests the risks Chief Executive Jeffrey Kindler and other industry executives face as they steer makers of traditional pills more deeply into biotechnology drugs.

The world’s largest drug maker by sales said it is pulling Exubera, a biotech medication that offers diabetes patients an alternative to injected insulin, after the product recorded a disappointing $12 million in sales this year, in part due to concerns among doctors about its long-term safety. Earlier the company predicted the drug would be a $2 billion-a-year product.

Drug companies often cancel drugs during human trials, and occasionally after they go on the market if there are any red flags about safety. But to pull a new drug from the market because it didn’t sell — in the absence of a red flag — is almost unprecedented.

“This is one of the most stunning failures in the history of the pharmaceutical industry,” said Mike Krensavage, an analyst at Raymond James & Associates. “I hope it would give Pfizer pause about buying any more assets.”

During a conference call with analysts, Mr. Kindler said yesterday that he would take a hard look at how his company could have made such a mistake, which contributed to a sharp decline in the company’s third-quarter earnings. “We will, of course, evaluate closely what happened here,” Mr. Kindler said. He added, “When I started this job it was clear that this business needed to be fixed in a lot of ways.”

Mr. Kindler added that Pfizer is canceling plans to develop a next-generation inhaler. Pfizer declined to make executives available for an interview.

The company’s stock slipped a penny yesterday to $24.54 in 4 p.m. composite trading on the New York Stock Exchange.

Pharmaceutical makers are desperate to replace chemical-based medicines whose patent protections are expiring. Lacking new drugs, they are making big investments in fancy ways to deliver existing ones or are plunging into development of so-called biologics, or large-molecule drugs. Pfizer deepened its commitment to biologics earlier this month, announcing that it would open a research facility in the San Francisco area. A biologic is a protein made in living cells out of genetic material.

Shifting to biologic drugs is a complex and costly endeavor. Making insulin, for example, usually requires specialized facilities that turn genetically engineered bulk insulin crystals into a purified liquid or powder. Inhalers use much more insulin than syringes, because much less of the drug makes it into the bloodstream, which means manufacturers have to produce much more bulk product. By contrast, many so-called small molecules, or pills, can be made out of standard chemicals in the same plant using the same equipment.

Exubera typifies the challenge. Pfizer launched the product in July 2006 with a limited push to doctors who specialize in diabetes. It projected the drug could hit $2 billion by 2010. But the unwieldy device, a tube about the size of a flashlight, drew unfavorable reviews from the outset from doctors and investors.

The path that ended yesterday began in 1996, when Pfizer struck a deal with a precursor to Nektar Therapeutics, which was studying inhaled insulin. The idea was that diabetics didn’t like to prick themselves with needles several times a day to deliver the insulin they need to balance their blood sugar, and would welcome a convenient inhaler that they could load with drugs and puff.

People familiar with Pfizer’s thinking at the time say the drug’s biggest hurdle was thought to be whether insulin could be delivered into the blood stream by an inhaler in a way as consistent as with a standard needle and syringe. When the device cleared that hurdle, Pfizer threw its effort behind the project, with highly visible backers such as then-Chief Executive Henry “Hank” McKinnell and Karen Katen, who later became president for human health and one of Mr. Kindler’s rivals for the top job.

In 1998, Pfizer teamed with German company Hoechst Marion Roussel AG to make the insulin, and pledged to build a Frankfurt plant that would employ 200 people. Pfizer declined to say how much it spent on the Frankfurt facility and another in Terre Haute, Ind., but told investors yesterday that it would write off $454 million in fixed assets and $661 million in inventory. The charges sent its third-quarter profit down 77% to $761 million, or 11 cents a share, on revenue of $11.99 billion.

Paris-based Sanofi-Aventis ultimately bought the German company and assumed its relationship with Pfizer, and the two companies presented Exubera to the U.S. Food and Drug Administration in 2005. At a meeting with analysts the following year, Ms. Katen told investors that their average forecast for Exubera sales in 2010 — $1.15 billion — was too low; Pfizer put it closer to $2 billion. World-wide sales for all insulin in 2006 were $8.7 billion, according to Credit Suisse.

But the concept of inhaling insulin was dogged by safety concerns, and regulators took a tough stance in reviewing the product. At issue: only about 10% of the insulin inhaled gets into the bloodstream, raising the question of what long-term effect the other 90% might have on the lungs.

Last year, Exubera finally cleared regulatory review but with a label that cautioned against its use by smokers or asthmatics and recommended regular lung exams. Pfizer bought out Sanofi’s share of the product for $1.3 billion.

Exubera’s problems continued. Although the drug was approved in January, it wasn’t introduced fully until September because of manufacturing problems. Once on the market, diabetes specialists said it was hard to use. Patients need to insert packets of powder into the device measured in three or nine milligrams — not the units doctors are used to. The company had problems getting insurance companies to cover the treatment at a favorable rate, and a British medical committee said Britain’s health authorities shouldn’t pay for it at all because it didn’t offer advantages over less-expensive therapies. Exubera costs about $5 a day while injectible insulin costs about $2 to $3 a day.

The Exubera device, which some compared unflatteringly to a bong for smoking marijuana, could also be embarrassing to use in public.

“I can teach someone how to use an insulin pen in five minutes, but it would take nearly an hour to teach a patient to use inhaled insulin,” says Anastassios Pittas, an endocrinologist at Tufts-New England Medical Center.

Pfizer said on the call with analysts yesterday that Exubera struggled because patients were resistant to beginning insulin therapy early in their disease, and were reluctant to visit the doctor for the lung-function tests required by regulators.

Still, Pfizer promoted the drug until the bitter end. In July, the company rolled out slick television commercials with the catch line “Now I get it,” to get patients comfortable with the inhaler. Earlier this week, Exubera was introduced in Canada.

Pfizer said yesterday that it will work with doctors over the next couple of months to move patients off Exubera. The company won’t lay off more salespeople, after cutting its sales team by 20% within the past year, but is considering what to do with its facilities in Germany and Indiana. It said 600 people are on paid leave at the Indiana plant pending that decision.

The news that Pfizer was abandoning Exubera came as a surprise to Nektar of San Carlos, Calif., from which Pfizer licensed Exubera. Nektar issued a scathing news release late yesterday accusing its partner of a poor marketing job and of not alerting Nektar it would be terminating their licensing deal. Pfizer says it told Nektar of its plans minutes after releasing the news, because the announcement was material for both companies.

Also up in the air is the market for other inhaled-insulin products still in development. Part of Exubera’s problem — the safety concerns that come with inhaling a drug — will be hard to surmount for any product that goes into the lungs, in the absence of long-term data. There is also the question of whether patients want to inhale insulin, or are really resistant to needles. In the 11 years since Pfizer bought into the idea, insulin pens have made injecting the drug less painful than the traditional needle and syringe.

It remains unclear whether other inhaled-insulin products can succeed where Pfizer’s drug failed. Eli Lilly & Co. plans to seek marketing approval from the FDA for its inhaled insulin in 2009. Lilly President John Lechleiter defended his company’s product and the need for an insulin inhaler on a call with investors yesterday. Lilly’s device is much smaller than Exubera, about the size of a cellphone. It comes in more understandable dosages that convert easily with standard insulin, Lilly says. Credit Suisse forecasts the product’s 2012 sales at $500 million.

NovoNordisk A/S and Abbott Laboratories are also in the running. NovoNordisk, which hopes to file its device for FDA approval in 2009 or 2010, uses liquid aerosol insulin instead of powder, which it says can cause patients to cough. Its device is slightly bigger than Lilly’s but lets patients choose a wider range of dosages.

Write to Avery Johnson at avery.johnson@WSJ.com