AA&MDSIF - FDA warning information

Medicare Coverage for Growth Factors

Note: this page will be updated as developments occur, so please check back often.

On May 14, 2007, the Centers for Medicare and Medicaid Services (CMS) issued a "Proposed Coverage Decision Memorandum for the Use of Erythropoiesis Stimulating Agents (ESAs) in Cancer and Related Neoplastic Conditions." Many MDS patients are currently being treated with ESAs or growth factors (Procrit, Epogen, and Aranesp), reducing or eliminating their need for transfusions. CMS proposed to stop paying for ESAs for the treatment of MDS as well as other non-bone marrow failure conditions, yet research supports the use of ESAs for patients with bone marrow failure. The AA&MDSIF strongly objected to this proposal. On July 30, CMS issued its final decision in which it reversed its original proposal that Medicare beneficiaries with MDS could not receive ESAs. The policy does, however, allow local Medicare contractors to develop their own "reasonable and necessary" policy on coverage of ESAs for MDS (and other conditions not included in the NCD). Some carriers have implemented policy changes; the Foundation has been monitoring these changes and will comment as appropriate.

The complete background information on this issue and the actions the AA&MDSIF has taken on behalf of patients who benefit from growth factors are outlined below.

FDA Change to Safety Information for Erythropoiesis-Stimulating Agents (ESAs) Results in Policy Changes from Medicare

On March 9th, the Food and Drug Administration (FDA) issued a strict warning on the overuse of growth factors or erythropoiesis-stimulating agents (ESAs) for the treatment of anemia after studies showed that ESAs caused dangerous and life-threatening side effects, such as increased tumor growth and heart attacks, in cancer and kidney patients with anemia. These studies, however, did not include patients with rare bone marrow failure diseases and their findings do not appear to be relevant to bone marrow failure.

A "black box" warning was then added to the label for Aranesp, Epogen, and Procrit with instructions for the doctor to prescribe the lowest dose necessary to keep the patient from needing a blood transfusion. The FDA also announced that it would bring this issue to the attention of the Oncologic Drugs Advisory Committee (ODAC) at its May 10th meeting. ODAC members would provide the FDA with their input into a need for more changes to the drug's label as well as a need for more studies on the safety of the drug. (Drug "labels" can be thought of as detailed "instructions" about the drug. Labels explain what studies have been conducted on the drug, what diseases the drug treats, what side effects are known, how the drug is thought to work, what precautions should be taken, and so on. All drug labels must be approved by the FDA.)

ESAs, which promote red blood cell growth, are currently approved by the FDA for use in patients with chronic kidney failure who have anemia and in cancer patients who have anemia from chemotherapy. It is prescribed "off-label" for patients with bone marrow failure diseases (i.e., the FDA has not approved a label that includes the use of ESAs specifically for bone marrow failure). Because the use of ESAs for MDS is supported by research findings published in the USP-DI, a drug compendium that Medicare, by law, uses to determine what drugs it will or will not pay for, Medicare has covered ESAs for MDS. (Many private insurance companies also use similar publications to determine what drugs they will cover, or they simply follow Medicare's policies.) As a result of the new black box warning, several regional Medicare carriers have announced in recent days that they will no longer pay for ESAs unless it is used according to the FDA-approved label and revised dosing instructions. The carriers' action may affect people with rare bone marrow failure syndromes as well.

What this Development Means for MDS, Aplastic Anemia and PNH Patients
Because bone marrow failure patients rarely reach hemoglobin levels >12 with the growth factors and because the problems with growth factors seem to be at levels above 12, the consensus from experts in hematology is that MDS patients do not generally share the same risks as patients who were part of the ESA studies. Moreover, there have been some studies of ESAs in bone marrow failure patients that do not indicate any harm. In addition, clinical practice guidelines published by the American Society of Clinical Oncology and the National Comprehensive Cancer Network also support certain uses of ESAs for treatment of myelodysplasia in select patients. More studies on ESAs in bone marrow failure patients would help to better understand the drug and its impact on this unique patient group. (AA&MDSIF encourages patients, with consent from their physician, to participate in approved clinical trials that foster our understanding of treatment options for MDS.) Until then, if you have been taking growth factors, talk to your doctor about your situation: the warning from the FDA must be assessed for each individual patient with bone marrow failure.

The ODAC Meeting
The FDA's Oncologic Drugs Advisory Committee met on May 10 to discuss the off-label use of ESAs. The Foundation, in its role as an advocate for patients, attended the entire ODAC meeting; board member John Theriault whose father has benefited from ESAs, presented the Foundation's statement. The Foundation's position is simple: the studies that concerned the FDA�with good reason�do not apply to people with bone marrow failure and bone marrow failure patients do not have the same risk factors as the cancer and kidney patients in the data examined by the FDA. Moreover, in looking at the risks and benefits of ESAs for MDS patients, there is generally a greater benefit than risk.

The FDA firmly noted in the hearing that its focus was only on patients who took ESAs to treat anemia due to chemotherapy for cancer, not people with bone marrow failure. In fact, an FDA staffer clearly stated that the issues with cancer are not relevant to MDS; the two are completely different diseases. Moreover, he said that the FDA would work with the Centers for Medicare & Medicaid Services (CMS) to make sure that coverage for ESAs will not be "swept away" for people with MDS. Hence, while ODAC members voted in support of label changes for ESAs and in support of more studies about the safety of ESAs in cancer patients, these actions are not meant to affect people with bone marrow failure. In other words, if your doctor thinks that you need growth factors to raise your hemoglobin to a safe level and you do not have the same risk factors as cancer and kidney patients, based on what we know now, the FDA actions are not likely to affect your doctor's decision.

Changes in Medicare
In March, the CMS opened a National Coverage Analysis (NCA) to evaluate the uses of ESAs in off-label or non-approved indications. CMS accepted all public comments submitted by April 13 (the end of the 30-day period), including those comments submitted by the Foundation on behalf of all bone marrow failure patients. On Monday, May 14, CMS issued its proposed decision memo in which it recommended, much to the surprise of the hematology community, not covering ESAs for anyone with MDS. The Foundation firmly believes that the CMS proposal is not supported by science: in fact, the use of ESAs for MDS is well supported by numerous studies. Moreover, the problems with ESAs seen in kidney and cancer patients are not seen in MDS patients, so, although not everyone with MDS needs ESAs or responds to ESAs, for many, many patients, ESAs are a crucial part of treating MDS. The AA&MDSIF is not aware of any scientific information that justifies not covering ESAs for MDS.

The Foundation also objected to the process CMS used to formulate its decision: CMS disregarded the scientific evidence we and other organizations included in our initial letters, even though the agency is supposed to consider all such comments, especially comments that include "clinical studies and other scientific information relevant to the technology under (consideration)." We also found the timing problematic: CMS issued the memo a mere two business days after the hearing of the FDA's Oncologic Drugs Advisory Committee and did not wait for that panel of experts to weigh in on the matter.

The AA&MDSIF again submitted comments to that effect on the proposed coverage policy, along with hundreds of other individuals and organizations, to CMS by the deadline of June 13. CMS reviewed the comments and issued its final decision on July 30. As noted above, CMS chose not to remove coverage of ESAs for MDS and reversed its original proposal that Medicare beneficiaries with MDS could not receive ESAs. The policy does, however, allow local Medicare contractors to develop their own "reasonable and necessary" policy on coverage of ESAs for MDS (and other conditions not included in the NCD), some carriers have implemented policy changes. The Foundation has been monitoring these changes and will comment as appropriate. Yet for many people, Medicare coverage on ESAs for MDS remains the same. Still, the AA&MDSIF is troubled by the different policies around the country and believes a uniform policy, grounded in science, is ideal. Yet there are not now enough studies to support a national coverage decision. More data are needed. To that end, the Foundation's Chairman of the Board of Directors and Chairman of the Medical Advisory Board wrote a letter to Amgen (the manufacturer of ESAs) and a letter to Ortho Biotech Products (a marketer of an ESA) as well as a letter to Johnson & Johnson (the parent company of Orth Biotech) calling on the companies to conduct the studies necessary to answer the unresolved questions on the use of ESAs in bone marrow failure diseases.

More information on Medicare's review can be found at CMS Tracking Sheet and at CMS Press Releases.

The American Society of Clinical Oncology (ASCO) has provided information about the Medicare Policy changes, including a list of carriers that have changed their policy.

The American Society of Hematology (ASH) has also provided information.

If you are unable to receive your medication, you can take the following actions:

If your doctor says that he/she cannot give you the growth factor because Medicare will not pay for it and if it is still medically appropriate for you to get the growth factor, ask your doctor to contact the carrier in your region to make sure that they understand your diagnosis. There is likely to be some confusion over coverage for MDS.
If that step is not effective, you can call AMGEN's Reimbursement Hotline at 800.272.9376 or Ortho Biotech's PROCRIT Line at 800.553.3851.
Inform the AA&MDSIF of any problems you encounter getting growth factors, especially if you are told that your local Medicare carrier has changed its policy. We can see whether or not the denial is in line with the local carrier's policy. If so, we can then talk to you about appealing the denial to your Medicare carrier.