Amgen Revives Defunct Drug as Old Therapies Seek New Cure

Amgen Inc.’s experimental drug rilotumumab, set aside by the company after it disappointed in a study, has been revived after a fresh look at data in gastric cancer found it helped a group of patients.

Rilotumumab used with chemotherapy almost doubled the survival rate for patients with high levels of c-Met, a protein linked to cancer growth, Thousand Oaks, California-based Amgen said yesterday in a statement. The data, released in advance of the American Society of Clinical Oncology meeting that starts June 1 in Chicago, have spurred the company to pursue a late-stage trial of the drug, said David Chang, Amgen’s vice president of oncology development.

The results are part of a significant shift taking place in how drugs are discovered and who they’ll work best for, said Marc Boutin, executive director of the National Health Council, a Washington-based group of patients’ advocates and health-care companies. This personalized medicine approach is becoming more important for drugmakers to reduce the time and cost of testing therapies and increase the chances of success, he said.

“Some of the early studies that were done with rilotumumab did not give us the level of evidence that would make us advance the program,” Chang said in an interview. “When the biomarker data came out, that tipped the balance.”

Amgen declined less than 1 percent to $70.54 at the close of trading in New York. The shares had gained 16 percent in the past 12 months.

Personalized Medicine

Personalized medicine involves determining whether a patient is genetically susceptible to a particular disease or would be especially responsive to certain treatments. More than 72 such therapies are available now, a fivefold increase from the 13 available in 2006, according to the Personalized Medicine Coalition, an industry advocacy group based in Washington.

Roche Holding AG’s breast cancer drug Herceptin was one of the first cancer medicines aimed at patients whose tumors have a particular genetic abnormality, known as HER2. In August, Basel, Switzerland-based Roche won U.S. regulatory approval for Zelboraf, a melanoma drug that works on patients whose tumors have a certain gene mutation. Both have companion diagnostic tests to determine if patients have the biomarkers.

The initial results from Amgen’s rilotumumab study in gastric cancer patients, released last year, showed the drug in combination with chemotherapy improved progression-free survival 33 percent, to 5.6 months from 4.2 months. Chang said that alone didn’t seem to warrant a larger, costlier study of the therapy, which Amgen, the world’s biggest biotechnology company, acquired a decade ago when it purchased Immunex Corp. for $16.8 billion.

Closer Review

The company analyzed the data further and found patients with high levels of c-Met, or MET, showed better results. C-Met is a protein that plays a vital role in spurring embryos to grow as well as healing wounds in adults. It is activated when bound together with another protein, hepatocyte growth factor/scatter factor. The process can go awry and create runaway cancer cells. Rilotumumab blocks the two from attaching.

Gastric, or stomach, cancer killed 736,000 people worldwide in 2008, second only to lung cancer, according to the World Health Organization. The American Cancer Society estimates there will be 21,320 new cases in the U.S. this year.

Rilotumumab and chemotherapy drugs extended the survival rate for gastric cancer patients with high MET expression to 11.1 months compared with 5.7 months for similar patients taking a placebo and the chemotherapy drugs, Amgen said in the statement and a summary of the study. Individuals with low MET expression tumors did worse on the therapy.

“That’s when we had a little bit of an ‘ah ha’ moment,” Chang said.

Different Targets

Len Lichtenfeld, deputy chief medical officer for the American Cancer Society, said advances in gene sequencing mean new cures may be found among older medicines or compounds that companies may have given up on.

“There are a whole slew of drugs and chemicals sitting on the shelves of companies, that have been looked at in the past, and probably need to be re-examined,” Lichtenfeld said in a telephone interview.

Pfizer’s lung cancer drug, Xalkori, approved last year, also only works for patients with a certain gene abnormality. While 1 percent to 7 percent of non-small cell lung cancer patients have this genetic aberration, the medicine reduced tumor size in 57 percent of those patients and stopped progression of the disease in 87 percent.

Journal Article

Pfizer only refocused its clinical trials on patients with this particular abnormality after reading an article in the medical journal Nature detailing it in 2007, said Robert Sweetman, the New York-based drugmaker’s senior director of U.S. medical affairs, oncology.

“We were totally able to stop the ship in mid-ocean and reverse course,” Sweetman said in an interview.

Pfizer’s drug also appears to stop several deadly children’s cancers driven by the same gene abnormality, according to initial study results reported yesterday in advance of the cancer meeting.

Prior to having the tools to sequence tumors quickly and cheaply, researchers might look at demographic data to determine why some patients did better than others on certain medications, he said. Now they can try to figure out beforehand which patients will respond best.

“I think there’s pretty wide agreement that the days of finding medicines that will work for tens, in not hundreds of millions of people at a time are probably over,” said Boutin, of the National Health Council.

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