• 8/1/2007
  • New York, NY
  • Marilyn Chase
  • Wall Street Journal Online (ww.wsj.com)

Advocates Beat Back Effort To Limit Use of Popular Drugs That May Carry Heart Risks

The Centers for Medicare and Medicaid Services — amid pressure from patient advocacy groups, medical societies and legislators — released new rules on its coverage of anemia drugs that are significantly less stringent than what the agency had originally planned.

The proposed changes, aimed at improving patient safety, had caused a public uproar for the past two months. More than 2,600 public comments were filed, many complaining that the proposals were Draconian and threatened to compromise patients’ quality of life by withholding needed treatment.

The new guidelines apply mostly to people with cancer who are receiving chemotherapy that causes anemia — a lack of red blood cells that ferry oxygen around the body. They also apply to myelodysplasia, a disorder of the bone marrow. Anemia can cause crushing fatigue, shortness of breath and cardiac arrhythmia.

The anti-anemia drugs — Amgen Inc.’s Epogen and Aranesp and Johnson & Johnson’s Procrit — were hailed a decade ago as alternatives to blood transfusions, which despite improved screening still carry a small risk of infections and immune reactions. But recent research has suggested that overuse of these drugs — known medically as erythropoiesis-stimulating agents, or ESAs — may carry serious risks.

A number of studies show increased cardiovascular risks among patients on the drugs, and raise questions about whether they fuel the growth of tumors in cancer patients. The Food and Drug Administration recently required new warnings on the drugs’ labels about the risks, helping spur CMS to consider limiting use.

Under the new guidelines, CMS will pay for treatment with ESAs only when hemoglobin — a measure of red blood cells — is less than 10 grams per deciliter of blood. Previously proposed restrictions would have forced doctors to wait until hemoglobin dropped below 9 — a level protested as too severe by many doctors and medical organizations. In men, the normal range is from about 14 to 18; in women, 12 to 15.

“Our goal was to maintain physician autonomy while ensuring the safety of our Medicare beneficiaries in light of FDA boxed warnings,” said CMS Acting Deputy Administrator Herb Kuhn in a prepared statement issued late yesterday.

Another issue on which CMS relented was its earlier statement disallowing treatment for a bone-marrow disorder called myelodysplasia. CMS earlier had said MDS patients would be covered only if they were part of a patient database. The final rule imposes no federal restriction, but leaves up to local contractors that provide CMS coverage whether to cover MDS treatment — a use of anemia drugs that isn’t formally approved by FDA but that has become part of standard medical care.

CMS currently spends about $5.4 billion a year on ESA treatment, which is used for correcting not only anemia related to chemotherapy and bone-marrow disease, but also due to kidney failure and dialysis. Kidney patients are covered by separate CMS rules and will come up for a hearing this fall by an FDA advisory panel.

To be sure, the Medicare agency still seeks to curb what it sees as risky or excessive use of anemia drugs. The rules disallow coverage of ESAs to treat any anemia of cancer that isn’t related to chemotherapy, or that results from radiation therapy alone. In addition, CMS says it won’t cover any use of ESAs for anemia-related to vitamin or mineral deficiency, or ESA use to prevent chemotherapy-induced anemia. It also ruled out treating patients with leukemia, uncontrolled hypertension, or certain other conditions where it is feared the drugs might hurt more than help.

The decision by CMS has been closely watched, in part because patients left anemic by chemotherapy or bone-marrow disorders say the treatment not only helps them avoid transfusions, but also enables them to regain a modicum of energy needed to lead a normal life.

Edward Shelton, a 43-year-old San Francisco math teacher, says this spring, his energy had crashed. Going to the supermarket after work overwhelmed him. He forgot why he walked into a room. He took to using a calculator for simple problems he once worked out in his head. “I was feeling really awful [and] out of breath,” he recalls.

An annual checkup found Mr. Shelton was anemic. His hemoglobin level in April was about 10 grams per deciliter of blood.

Mr. Shelton’s hemoglobin had fallen to 9 by a follow-up visit in May, and a race was on: His doctor prescribed him injections of an anti-anemia drug. But Mr. Shelton’s levels fell further before he could begin the drug, and he wound up requiring a blood transfusion. He eventually did begin taking Procrit, which he says gave him his life back. But he would have preferred to avoid the transfusion, which took about six hours — or most of a work day — to complete.

Experiences like Mr. Shelton’s help illustrate the concern many doctors have had about waiting too long to begin anti-anemia drugs.

Samuel Silver, chairman of the subcommittee on reimbursement of the American Society of Hematology, had gone to Washington in recent days to negotiate with CMS. Late yesterday he cheered signs that the agency was responsive to medical concerns. “It appears that they listened to the scientific arguments that were made,” says Dr. Silver, who is also professor of internal medicine at the University of Michigan, Ann Arbor.

Both ASH and the American Society for Clinical Oncology had protested the earlier proposed changes. A spokeswoman for ASCO said the society’s leadership was still digesting the new 61-page CMS coverage decision, and hadn’t had time to study the changes. Both ASCO and ASH receive funding support from the makers of ESA drugs, but said their concerns stemmed from a desire to preserve doctors’ medical decision-making and patients’ access to care.

Joseph Bailes, chairman of ASCO’s government-relations council, has noted previously that Medicare and Medicaid decisions touch off wider ripples and eventually affect most Americans in the form of similar restrictions by private insurers.

Even before CMS finalized its rules, at least one insurer, Blue Shield of California, had adopted some of the new CMS guidelines for its 3.3 million members.

“Our concern was that the dosage has been too high and there are high risks from side effects,” a Blue Shield spokesman said.

The impetus for the change is research highlighting a number of risks with the anti-anemia drugs. Last fall, two New England Journal of Medicine studies found that chronic kidney-disease patients were more prone to hypertension, strokes and heart attacks when treated aggressively with these drugs.

Early this year, two more findings increased concerns. In one study, cancer patients with anemia not linked to chemotherapy or radiation who took the drugs experienced more deaths than those on a placebo. The other study, focused on patients with head and neck cancer, found that adding Aranesp to radiation therapy was linked with worse localized tumor progression and a small increase in deaths.

Amgen and J&J had noted that most of the problems have been linked to studies that pushed hemoglobin targets higher than 12 — which is the target for which the drugs are approved by the FDA — suggesting excessive dosage is the culprit.

The drugs’ makers had argued against the proposed changes at CMS for months. In Thousand Oaks, Calif., a spokesman for Amgen said, “We are continuing to review the CMS decision and will work cooperatively with CMS to ensure that patients receive the treatment they need.” A spokeswoman for J&J’s Ortho Biotech unit said yesterday that management was still studying the new rules. Some observers yesterday said they would have preferred that CMS wait and not come out with a decision before the FDA issues its own additional guidance on ESAs, which is expected following an oncology advisory committee meeting.

The cancer community wasn’t unanimously opposed to a tightening of CMS rules. James Doroshow, who heads the division of cancer treatment and diagnosis at the National Cancer Institute, said in an interview on the New England Journal of Medicine Web site that he would use anemia drugs in patients with hemoglobin of 8 to 9, especially where heart disease makes transfusions inappropriate. But he said he would avoid using them in cancer patients with higher hemoglobins or who had certain tumors.

Among the avalanche of protests preceding yesterday’s concessions, members of Congress had also sent the agency letters weighing in on the issue. In one letter, a bipartisan group of 46 senators acknowledged problems with overuse, but had said the originally proposed restrictions as written would have denied appropriate treatment and required too many chemotherapy patients to rely on blood transfusions.