Today’s New York Times is running a story by Alex Berenson in the business section about Genentech’s Avastin, A Cancer Drug Shows Promise, at a Price That Many Can’t Pay. “Doctors are excited about the prospect of Avastin, ” Berenson writes, “a drug already widely used for colon cancer, as a crucial new treatment for breast and lung cancer, too. But doctors are cringing at the price the maker, Genentech, plans to charge for it: about $100,000 a year.”

“That price, about double the current level as a colon cancer treatment, would raise Avastin to an annual cost typically found only for medicines used to treat rare diseases that affect small numbers of patients. But Avastin, already a billion-dollar drug, has a potential patient pool of hundreds of thousands of people — which is why analysts predict its United States sales could grow nearly sevenfold to $7 billion by 2009.

Doctors, though, warn that some cancer patients are already being priced out of the Avastin market. Even some patients with insurance are thinking hard before agreeing to treatment, doctors say, because out-of-pocket co-payments for the drug could easily run $10,000 to $20,000 a year. “

The Food and Drug Administration approved Avastin for patients with advanced colon cancer in 2004 after trials showed that it extended these patients’ lives by a median of 5 months.

What Berenson’ story buries on its second page is that Avastin came under scrutiny this week after unexpected patient deaths caused suspension of enrollment in a study to see if this drug helps prevent colon cancer recurrence. The group of patients in question were taking Avastin along with another chemotherapy regimen, XELOX (Capecitabine Plus Oxaliplatin). Since the trial began in December 2004, seven patients taking that combination died, four of them suddenly, Roche said in a press release.

Paul Elias reported yesterday in the Miami Herald, “Drug companies stop recruiting for cancer drug test after deaths.” See also Bloomberg News, Deaths During Roche Clinical Test Slow Program, February 13. The Times, too, carried this story yesterday in the business scetion as written by the Associated press (Deaths Halt Enrollments in a Drug Trial).

Berenson in the Times writes today:

Studies show that Avastin can prolong the lives of patients with late-stage breast and lung cancer by several months when the drug is combined with existing therapies. Genentech expects to seek federal approval later this year to sell it specifically for those diseases. But even now, doctors, who are free to prescribe the drug as they see fit, are using Avastin for some breast and lung cancer cases — and finding its cost beyond the means of some patients.

“Avastin is a superb drug, but its cost is already discouraging patients and doctors from using it,” said Dr. David Johnson, who heads the cancer unit at Vanderbilt University and is a former president of the American Society of Clinical Oncology. “I wish it were one-tenth the cost, and if it were I would be giving it to almost everybody.”

With colon cancer, a year of Avastin treatment costs about $50,000. But the drug will be used at higher doses for lung and breast cancer, and Genentech does not plan to reduce the unit price, even though the additional cost of producing a higher dose is minimal. Roche executives described the pricing plans were described in a recent interview.

Because Genentech is a leading developer of cancer therapies, some doctors also fear that the company’s pricing plans for Avastin — around $8,800 a month — may encourage other companies to charge more for their own oncology drugs. That could potentially drive up the overall cost of cancer treatment to unsustainable levels, they say.

Only on the next page does a reader see that Berenson knew about the deaths before choosing price as his lead. “Earlier this week Roche stopped recruiting patients for one clinical trial that included Avastin,” he writes, “while researchers try to explain the deaths of several patients. But doctors generally view Avastin as one of the safest cancer treatments. About 200 clinical trials including Avastin are taking place worldwide.”

Then it’s back to the billions this drug is expected to earn: “With Avastin’s expanded use, analysts expect the drug’s sales to soar to $7 billion in the United States alone by 2009, compared with $1.1 billion last year. Over the same period, Genentech’s overall profits are forecast to triple, to $4 billion in 2009, as sales — $6.6 billion last year — climb to $18 billion.

“They are certainly blazing new ground with the price of the drug,” said Geoffrey C. Porges, an industry analyst at Sanford C. Bernstein & Company. “They’re saying, we think this is fair value, at least on a relative basis.”

And it could that patients are paying to much for the drug through failure to test whether lower doses are sufficient. Berenson writes:

The higher cost of using Avastin in breast and lung cancer, compared with colon cancer, is a result of cancer drugs’ being priced on the basis of weight. In colon cancer, Genentech tested Avastin at a dose of 5 milligrams of the drug per kilogram — or 2.2 pounds — of the patient’s body weight. But in lung and breast cancer, the company tested the drug at a dose of 10 milligrams per kilogram of body weight.

Because the actual cost of producing Avastin is a fraction of what Genentech charges for it, some analysts and doctors had expected the company to lower Avastin’s price per milligram for use in lung and breast cancer.

Dr. Leonard Saltz, an oncologist at Memorial Sloan-Kettering Cancer Center in New York, noted that Genentech had not tested the Avastin at the dose level for colon cancer in large-scale trials of lung and breast cancer. As a result, no one really knows whether the lower dose might turn out to be equally effective in lung and breast cancer, he said. Besides costing less, he said, a lower dose might have fewer side effects.

“There are no meaningful data to allow us to address that question,” he said.

Dr. Desmond-Hellmann said that Genentech was assuming that some cancer doctors might, in fact, use Avastin at the lower dosage to treat breast and lung cancer. That is a reason the company does not want to lower Avastin’s per-milligram price, she said, because doing so would cut too deeply into revenues if doctors do not prescribe the higher doses that were used in the breast and lung cancer trials.

“We don’t actually know whether physicians will actually use Avastin as was used in the clinical trials,” she said.

But Dr. Saltz and other doctors said that they would almost certainly stick to the higher Avastin dose that was tested in the clinical trials, for fear that a lower dose might not be as effective.

Clinical trials are supposed to establish the most effective dose with minimum side effects. From Berenson’s account, it sounds like Genetech is so profit-driven that it may be using clinical trials to establish not the safest and most effectoive but the most profitable dose. And using fear to drive profits. Let’s hope that’s not why more deaths than expected occured in the colon cancer clinical trial.

Avastin side effects, manufacturer’s patient brochure.