Will New Anemia Drug Top Current Treatments?

A new drug designed to treat patients with a rare form of anemia could possibly have wider applications, perhaps replacing other anemia treatments that have been linked to an increased risk of death, cancer and stroke, experts say.

The drug, Hematide, was successful in treating patients who have pure red-cell aplasia, a condition caused by antibodies to a hormone needed to produce red blood cells. It's a "devastating condition that many patients have died from and ties patients to blood transfusions every two weeks for the rest of their life," said lead researcher Dr. Iain C. Macdougall, from King's College Hospital, London.

But the real breakthrough is being able to make drugs in a new way that could have wide application for many diseases, he said.

"It is possible to create drugs that are cheaper and simpler to make," he said. "The question is whether all expensive protein therapeutics can get peptide mimetics. This is what we call a peptide mimetic -- it mimics the protein," he said.

The report is published in the Nov. 5 issue of the New England Journal of Medicine.

For the study, Macdougall's group treated 14 patients with chronic kidney disease who were anemic because of antibodies that prevented other anemia treatments from making red blood cells.

Twelve weeks after the first dose of Hematide, a synthetic peptide-based erythropoietin agonist, none of the patients needed blood transfusions, the researchers found. In addition, the amount of antierythropoietin antibodies decreased and in six patients became undetectable.

One patient developed antibodies to the drug and had to go back to receiving regular transfusions, the researchers noted.

Some experts think Hematide could replace other anemia drugs used to treat anemia caused by kidney disease or chemotherapy, if it turns out to have fewer adverse side effects. However, Macdougall is cautious about making such claims.

"That's speculation," he said. "There is no way our paper suggests that, and there is no hard scientific evidence that would suggest that."

Dr. H. Franklin Bunn, research director of the hematology division at Brigham and Women's Hospital and Harvard Medical School, both in Boston, and author of an accompanying journal editorial, said that "down the road this drug may have some advantages over regular erythropoietin drugs."

But he said it is too early to tell whether Hematide can replace the erythropoietin drugs Procrit and Aranesp, which are associated with heightened risk of heart attack, cancer and stroke.

For now, Hematide is "the treatment of choice for patients who have developed antibodies against erythropoietin. And that's all you can say at this point. but I am curious to find out whether this drug will be able to be used and be effective and safe in a wider setting," Bunn said.

Other experts are more optimistic. Dr. Charles Bennett, a hematologist/oncologist at Northwestern Memorial Hospital and Jesse Brown VA Medical Center in Chicago, said that "we are going to look at this in five years and see that it's a breakthrough paper."

It's hoped this drug will take the place of erythropoietin drugs and not have the side effects associated with them, Bennett said.

Dr. Jochen Reiser, chief of nephrology and hypertension at the Leonard M. Miller School of Medicine of the University of Miami, voiced similar hopes. "In some patients where Procrit has proven not to be beneficial, maybe this peptide has an additional potential that Procrit doesn't have or works better."

Whether Hematide will overcome the side effects associated with Procrit is still hard to say, Reiser said.

"If the side effects come from increasing the amount of red blood cells, then no, it would have the same effects, but if they are substance-related side effects that have nothing to do with the red blood cells, then yes -- that can be looked at now," he said.

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Study finds stroke risk from anemia drug Aranesp

A new study raises fresh safety concerns about widely used anemia medicines, finding that the drug Aranesp nearly doubled the risk of stroke in people with diabetes and chronic kidney problems who are not yet sick enough to need dialysis.

The study is the largest ever of these blood-boosting drugs and the only one that compared them to a dummy treatment. The medicines have become blockbuster sellers because they lessen the need for transfusions, but their ability to prevent heart attacks, kidney failure or other problems have not been proven.

Over the last two years, the federal Food and Drug Administration has repeatedly strengthened warning labels on Aranesp, Epogen and Procrit as concerns rose that they may worsen survival in certain cancer patients, especially at higher doses. Amgen Inc. of Thousand Oaks, Calif., makes all three drugs, although New Brunswick, N.J.-based Johnson & Johnson sells Procrit.

The new study tested Aranesp in a different group of patients: 4,038 people with Type 2 diabetes, kidney problems and moderate anemia — problems that often go hand in hand. The goal was to see if the drug could prevent heart attacks, heart failure, strokes or the need for dialysis.

It not only failed to do that, but "we uncovered a risk that I think is substantial for stroke," said study leader Dr. Marc Pfeffer, a heart specialist at Brigham and Women's Hospital in Boston.

Strokes occurred in 101 patients given Aranesp and 53 patients given dummy shots. Looked at another way, the risk of suffering a stroke was about 1 percent per year in the placebo group and about 2 percent in those given Aranesp.

For many people, "this risk will outweigh its potential benefits," the study's authors conclude.

Results were published online Friday by the New England Journal of Medicine and were to be presented at a conference of kidney specialists in San Diego. Amgen sponsored the study. Pfeffer has consulted for the company and two authors work for it.

Dr. Roger Perlmutter, Amgen's head of research and development, said the magnitude of stroke risk "surprised us." The potential risk of stroke has been listed on Aranesp's label since the drug was approved in 2001, but "we will definitely update the label" because of the new study's results, he said.

Aranesp did reduce the need for transfusions — 297 people on the drug needed them versus 496 of those getting dummy shots. However, there was only a modest improvement in how fatigued people said they felt in the Aranesp group.

The study's results may not apply to people already on dialysis, Dr. Philip Marsden of St. Michael's Hospital and the University of Toronto in Ontario, Canada, writes in an editorial in the medical journal. For them, the quality of life improvement from fewer transfusions may be greater.

Also on Friday, the New York Attorney General's office said it and 15 states were suing Amgen, claiming the company gave kickbacks and weekend retreats to medical providers to help boost Aranesp sales, and encouraged them to bill third parties, including Medicaid, even though the drug was available to them at no cost.

A statement by the company said the allegations were "without merit."

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Home Remedies for Anemia Treatment

Anemia is a blood disorder that occurs when the quantity of the red blood cells decreases in our body. Anemia generally means lack of blood. The Hemoglobin helps the red blood cells to carry the oxygen from the lungs to all other parts of our body. Also the formation of the hemoglobin depends on adequate dietary supplies of iron and protein and other nutrients. There are many home remedies for anemia treatment.


Some types of Anemia

* Iron deficiency anemia: It is the common type of the anaemia. Iron is also required for the formation of hemoglobin. When there is the less iron in the body it can causes iron deficiency anaemia.

* The Aplastic anaemia: basically It is caused when the body stops making enough red blood cells and the chances of infections increases to great extent.

* Underlying diseases: Such certain conditions can affect the formation of red blood cells to a great extent.

* Vitamin deficiency anaemia: This is also called megaloblastic anemia. This is mainly caused due to the deficiency of the folic acid or vitamin B12.

Home Remedies for Anemia treatment

* Eat 3-4 apples daily to increasing iron content in the body and it is one of the best home remedies for anemia treatment.

* Also vitamin B12 is necessary for both preventing and treating anemia. Some rich sources of vitamin b12 are animal protein and organic meats.

* Tea and coffee should be avoided as, tea and coffee hinder with the iron absorption.

* Beets juice contains potassium, phosphorus, calcium, iron, copper, protein, fat, and vitamins B1, B2, B6, C and P. So it is good for anemia cure.

* Cold-water bath are advisable daily. As it is very valuable method in anemia cure and best among home remedies for anemia treatment.

* The cold friction and the hot Epsom baths for 5-15 minutes once a week are advisable for anemia cure.

* Also Sunbaths are very beneficial as sunlight stimulates the production of red cells.

* The 3-4 dried figs are advisable day for anemic persons.

* Honey plays very important role in improving the health and in the anemia cure. The Lemon and honey or apple cider vinegar is beneficial when taken during the morning. These are some best home remedies for anemia treatment.

by : steven marks
Source : www.articlealley.com

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Expect FDA Approval of AMAG Pharmaceutical's Feraheme

expects the U.S. Food and Drug Administration (FDA) to decide on the marketing application of AMAG Pharmaceuticals, Inc.’s (AMAG) Feraheme (formerly known as Ferumoxytol), designed for the treatment of iron deficiency in anemia patients with chronic kidney disease (CKD), including dialysis dependent and non-dialysis dependent CKD patients.

Anemia is a condition of abnormally low levels of red blood cells (RBCs) in the blood and hemoglobin. Hemoglobin is a protein present in RBCs that is responsible for transporting oxygen to the body tissues. Deficiency of iron is one of the reasons behind the development of anemia in CKD patients.

Kidney disease eventually leads to kidney failure, a condition in which the kidney fails to perform its functioning of removing wastes from the body in the form of urine. Regular dialysis is required when both the kidneys have stopped working. Dialysis is a medical procedure of removing impurities and waste products from the blood, when the kidneys are unable to do so.

Feraheme, the lead pipeline candidate of AMAG, is being tested for the treatment of iron deficiency in anemia patients with CKD and as an agent to improve the visibility of internal bodily structures (contrast agent) during magnetic resonance angiography (MRA) in peripheral artery disease (PAD) patients. MRA is a non-invasive medical imaging technique, which is used to produce detailed three-dimensional images of the blood flow in the blood vessels.

PAD is a condition that reduces the blood flow in the legs.

Anemia is a major problem associated with CKD. Iron replacement therapy, currently available in both oral and intravenous/IV (injected in the veins) formulations, is the existing standard treatment for anemic CKD patients. However, oral iron replacement therapies are associated with various side effects (like diarrhea and cramping) and the injectable products take a long time to be administered.

If successfully developed and approved, Feraheme could emerge as the preferred iron replacement therapy for anemia patients with CKD, promoting safety and faster administration. We estimate the peak revenue potential of the drug at approximately $450 million, or 49.08% of the company’s current market capitalization.

Potential Impact:

Feraheme, the lead pipeline candidate of AMAG, is under evaluation for the treatment of iron deficiency in anemia patients with CKD (including dialysis dependent and non-dialysis dependent patients) as well as a contrast agent for MRA in PAD patients. On May 25, 2008, AMAG entered into an agreement with 3SBio Inc. (SSRX), whereby SSRX obtained the exclusive rights to develop and commercialize Feraheme for CKD in China. In addition to this, AMAG is exploring potential partnership opportunities for the drug in other countries.

In December 2007, AMAG filed a New Drug Application (NDA) with the FDA for the approval of Feraheme for the treatment of iron deficiency in anemia patients with CKD. In October 2008, the company received a Complete Response Letter (CRL) from the FDA for the drug. In this letter, the FDA requested for additional information regarding the clinical trial data of Feraheme that had been submitted by AMAG and the company subsequently provided the relevant information to the FDA. However, in December 2008, the FDA issued another CRL to the drug. AMAG responded by resubmitting the NDA of Feraheme. The next crucial event for AMAG, the decision on the marketing application of Feraheme by the FDA, is expected by June 29, 2009.

CKD is characterized by a decline in the kidney functioning of an individual for a period of 3 months or more. Anemia, an under-recognized but characteristic feature of CKD, is associated with severe consequences such as cardiovascular disorders, hospitalizations and can even lead to death in the advanced stage CKD patients. In fact, anemia becomes more prevalent as the kidney functioning declines in the advanced stages, ranging from approximately 27% in the initial stages of CKD to 76% in the most advanced stages.

Anemia occurs due to iron deficiency in CKD patients, who require iron replacement therapy to manage their condition. Currently, iron replacement therapies are available in both oral and IV formulations. Oral iron replacement therapies suffer from the problem of being poorly absorbed in anemic patients and have a poor tolerability profile, thereby causing side effects like diarrhea and cramping, often resulting in discontinuation of treatment. Though IV therapies are far more effective than the orally administered ones, they also suffer from certain limitations.

Some of the existing IV therapies like Venofer from Fresenius Medical Care AG & Co. (FMS)/Vifor International, a subsidiary of Galenica AG, which is a Switzerland-based company, and Ferrlecit from Watson Pharmaceuticals, Inc. (WPI)/Sanofi-Aventis (SNY) need to be administered slowly and periodically in small dosages to meet the total dosage requirement of patients. Most patients require a total of 1,000mg Venofer to obtain treatment benefit, however, this 1,000mg cannot be administered in a single administration. In non-dialysis dependent anemic CKD patients, the total dosage of Venofer is divided into 5 sub-dosages (200mg each), with each sub-dosage requiring 5-10 minutes for administration. These 5 sub-dosages are given at 5 different occasions distributed over a 14-day period. In dialysis dependent anemic CKD patients, the total dosage of Venofer is divided into 10 sub-dosages (100mg each) and each sub-dosage requires 5-10 minutes for administration. All these 10 sub-dosages are administered at 10 different occasions.

Ferrlecit is only approved for dialysis dependent anemic CKD patients and has to be furnished at a dosage totaling 1,000mg to show treatment effect. However, the entire dosage of Ferrlecit can also not be administered in a single administration and is broken into 8 sub-dosages (125mg each), with each sub-dosage taking approximately 10 minutes (which sometimes extends to 1 hour) for administration. These 8 sub-dosages are given over 8 consecutive dialysis sessions.

Another disadvantage of the IV therapies is that they are associated with rare and life-threatening anaphylactic reactions (severe, life-threatening allergic reactions, which are characterized by symptoms such as low blood pressure, wheezing, vomiting and diarrhea). All these factors have left the market open for more effective treatment options in development for this condition.

Feraheme demonstrates many benefits over the currently available iron replacement therapies. Previous clinical trials indicate that Feraheme does not cause the side effects associated with oral iron replacement therapies. Unlike the inconvenient dosing schedule of the existing IV iron replacement therapies, Feraheme can be rapidly administered in two 17-second injections. Moreover, no cases of serious anaphylactic reactions have been observed in the clinical trials of Feraheme. Driven by these advantages, Feraheme could emerge as a therapy of choice for anemia patients with CKD. The U.S. IV iron replacement therapy market (currently approximately $570 million) represents an attractive opportunity for AMAG, with approximately 354,000 CKD dialysis dependent patients and 1.6 million CKD non-dialysis dependent patients, being currently eligible for Feraheme treatment. We believe Feraheme could generate peak revenues of approximately $450 million, or 49.08% of the company’s current market capitalization.

Expectations:

We expect the FDA to approve Feraheme for the treatment of iron deficiency in anemic CKD patients, including dialysis dependent and non-dialysis dependent ones by June 29, 2009.

In December 2007, AMAG submitted the marketing application of the IV formulation of Feraheme for the treatment of iron deficiency in anemic CKD patients. The filing was primarily based on the data from three Phase III efficacy and safety trials and one Phase III safety trial.

Across all the Phases of the clinical trials, a total of approximately 2,800 dosages of Feraheme had been administered. However, there were no cases of anaphylactic reactions and no incidences of any drug-related deaths reported in the Feraheme patient group. Additionally, throughout the clinical trials, only three (0.17%) out of the 1,726 Feraheme patients experienced serious adverse events like cardiac problems, while one (0.35%) among the 289 oral iron replacement therapy patients and one (0.13%) of the 781 placebo patients experienced serious adverse events.

On October 20, 2008, the FDA issued a CRL to Feraheme, which reflected their view that the drug was not ready for approval. In the CRL, the FDA requested for additional information regarding the clinical trial data submitted by AMAG. The agency also asked for certain clarifications regarding its inspection of one of the Phase III trial sites of Feraheme in addition to raising a question regarding a pre-approval inspection of AMAG’s manufacturing facilities. AMAG indicated that all of these issues were addressable and submitted its response to the CRL on the basis of the existing clinical trial data and stated that no additional trial was needed to be initiated. The FDA accepted the response to the CRL on November 13, 2008 and assigned Feraheme a new approval date of December 30, 2008.

However, on December 22, 2008, AMAG announced that it had received a second CRL for Feraheme. This time also the FDA had raised some additional queries regarding the pre-approval inspection of AMAG’s manufacturing facilities. Additionally, there were some questions regarding Feraheme’s labeling-related decisions. Though the company is seeking an FDA approval of Feraheme for the treatment of iron deficiency anemia in all CKD patients, patients who are on dialysis and patients who are not on dialysis, it is the FDA who has to decide on the final labeling of Feraheme. In the CRL, the FDA mentioned that it is yet to take a final decision regarding the labeling of the drug.

On May 1, 2009, AMAG declared that all the outstanding issues related to the manufacturing sites of Feraheme had been successfully and satisfactorily settled with the FDA. Additionally, the company stated that it had successful interactions with the FDA regarding the content of the label of Feraheme. Given that all the manufacturing issues related to the drug have been resolved, the company is optimistic that the FDA will be able to take a final decision regarding the labeling of Feraheme.

On May 12, 2009, AMAG announced that their response to the second CRL has been accepted by the FDA and the agency has designated it a Class I resubmission, assigning it a new approval date of June 29, 2009.

Class I resubmission deals with minor application deficiencies, such as labeling issues, commitments to perform post-marketing studies, safety updates and other minor clarifying information. Class I resubmission starts a new 60 days review cycle.
Based on the fact that the company succeeded in satisfactorily answering the FDA’s queries regarding the manufacturing of Feraheme, the major concern of the agency, which was highlighted in both the CRLs, we are optimistic about the company receiving approval this time for Feraheme by June 2009.

The Product:

Chronic kidney disease (CKD) patients often suffer from anemia, a condition of abnormal reduction in the number of red blood cells (RBCs) and hemoglobin (the iron-containing protein present in RBCs) in the body. Hemoglobin carries oxygen to the body’s tissues.
The production of RBCs depends upon two factors: firstly a hormone called erythropoietin, which is produced by the kidneys, and secondly iron. Erythropoietin, after being released by the kidneys, travels to the bone marrow (the soft tissue in the center of bones, responsible for the blood cell production) via the blood. Upon reaching the bone marrow, erythropoietin stimulates RBC production. An adequate concentration of iron is also essential for the bone marrow to produce the hemoglobin part of RBCs since iron is an integral component of hemoglobin.
Both erythropoietin and iron should work together to produce the required amounts of RBCs in the blood. An imbalance in the erythropoietin and iron levels leads to anemia.
The diseased kidneys in CKD patients do not produce the required amounts of erythropoietin. As a result, the bone marrow produces lesser amounts of RBCs, which is insufficient to meet the body’s RBC requirement. Additionally, CKD patients suffer from increased iron loss due to inadequate nutrition (which results in poor dietary iron intake), blood loss caused by multiple blood draws, dialysis (if needed), gastrointestinal bleeding and surgical procedures. Iron deficiency and an inadequate supply of erythropoietin together make patients anemic.
Anemic CKD patients are often treated with Erythropoietin Stimulating Agents (ESAs), like Amgen Inc.’s (AMGN) Epogen, to increase the production of RBCs. ESAs are synthetic versions of the natural erythropoietin and function in a similar manner to the natural hormone. The initiation of ESAs result in rapid increase in the production of RBCs. Besides erythropoietin, iron is another prime requirement for the production of RBCs. Thus, the rapid increase in RBC production on the initiation of ESAs involves an increased usage of iron in the body. CKD patients have low levels of iron in the body. Long-term usage of ESAs depletes the existing iron reserves in these patients and the consequent iron deficiency limits the effectiveness of ESAs. As a result, the majority of CKD patients require iron replacement therapy to replenish their iron levels.
Feraheme, an intravenously (IV) administered iron replacement therapy, works to replenish the iron levels, which is lost in anemic CKD patients with iron deficiency.
Advantages of Feraheme:

Avoids the Side Effects Associated with Oral Iron Replacement Therapies – Oral iron replacement therapies have limited efficacy and they do not adequately increase the body's iron levels in anemic CKD patients. Additionally, oral iron replacement therapies are poorly absorbed in anemic CKD patients, resulting in unwanted side effects such as diarrhea and cramping, often leading to the discontinuation of treatment. In contrast, the IV formulation of Feraheme provides greater amounts of iron in anemic CKD patients, while avoiding the side effects linked with oral iron replacement therapies.
Rapid Administration and Less Frequent Dosing – The existing IV iron replacement therapies (like Venofer from FMS/Vifor International and Ferrlecit from WPI/SNY) need to be administered slowly and in small dosages over several sessions to meet the body’s total iron requirement. The recommended dosage of Venofer is 1,000mg, which cannot be administered at a single go.
In non-dialysis dependent CKD patients, the total dosage (1,000mg) of Venofer is divided into 5 sub-dosages (200mg each), with each sub-dosage requiring 5-10 minutes for administration. The 5 sub-dosages are given in 5 different occasions within a 14-day period.
In dialysis dependent CKD patients, the total dosage (1,000mg) of Venofer is divided into 10 sub-dosages (100mg each), with each sub-dosage administration requiring 5-10 minutes. All these sub-dosages are administered in 10 different occasions.
Ferrlecit, which is approved only for dialysis dependent CKD patients, has a recommended dosage of 1,000mg. Like Venofer, Ferrlecit cannot be given in single administration. The total dosage is broken into 8 sub-dosages (125mg each), taking approximately 10 minutes (which sometimes can extend to an hour) for administration of each sub-dosage. These 8 sub-dosages are given over 8 consecutive dialysis sessions.

In contrast, Feraheme is rapidly administered in two 17-second injections, making it more patient friendly.

The Market:

Chronic kidney disease (CKD) is the gradual and usually permanent loss of kidney functioning, which occurs as a result of physical injury or a disease (such as high blood sugar or high blood pressure) that damages both the kidneys. This loss of kidney functioning is gradual that may take even months or years. In CKD, the tiny filters in the kidneys (called nephrons) are damaged and the kidneys ability to remove wastes from the body gets declined.

Based on the severity of the disease, CKD is divided into 5 categories ranging from Stage 1 to Stage 5. Stage 5 is the most severe condition, which is characterized by total or near-total loss of kidney functioning and patients requiring dialysis or kidney transplantation to stay alive.

Anemia, an abnormal reduction in RBCs, is a rational consequence of CKD. This is because the damaged kidneys are incapable of producing sufficient amounts of erythropoietin, a hormone stimulating RBC production. Thus, CKD patients are at high risk for developing anemia and the treatment of anemia in CKD patients is extremely important to keep them healthy.

To increase RBC production, anemic CKD patients are treated with ESAs. The production of RBCs also requires iron, thus increasing the utilization of the existing iron stores of the body. The continuous usage of ESAs initiates an increased usage of iron in the body, thereby causing a progressive reduction in the body’s iron reserves, resulting in an iron deficiency. This decreases the effectiveness of ESAs as a treatment of anemia. Additionally, blood loss caused by multiple blood draws, surgical procedures, dialysis as well as due to gastrointestinal bleeding, reduces the iron levels in CKD patients. Therefore, a majority of CKD patients eventually develop iron deficiency anemia, requiring iron replacement therapy.

Source : seekingalpha.com

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AMAG says FDA accepts resubmission of anemia drug NDA

AMAG Pharmaceuticals Inc (AMAG.O) said U.S. health regulators accepted the resubmission of the new drug application for its experimental anemia drug ferumoxytol.

The U.S. Food and Drug Administration has designated the resubmission as a complete, Class 1 response, which typically means it will review the drug within a 60-day period.

AMAG, which received a second complete-response letter from FDA in December, said the FDA has set June 29 as a new target action date to complete the review of the drug.

The company, which received the first complete response letter from the FDA in October, is seeking approval for ferumoxytol to treat iron deficiency anemia in patients with chronic kidney disease.

Source : www.reuters.com

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