Anemia is common in dialysis-dependent kidney disease.
Most common reasons:
1. Iron deficient from (most common reason):
Supply: not eating enough, not bioavailable, can't tolerate oral iron
Loss: from constant blood draws and labs, GI bleeding, blood loss during dialysis and dialysis itself
2. Decrease in or lack of EPO
* EPO only works if bioavailable iron is present
3. Chronic inflammation / chronic disease
Addressing iron deficiency in many cases can correct anemia and obviate need for EPO. If a steady state of iron can be provided without see-saw pattern of iron levels then the amount of epo can be decreased and used at stable weekly levels. EPo resistance occurs bcz of receptor saturation but more often bcz of iron deficiency. So iron in itself not only can maintain hemoglobin levels but can increase effectiveness of EPO.
IV/parenteral, and oral iron supplementation are necessary. If the SFP iron is a bioavailable form, then there is no question that in a random group of dialysis-dependent chronic renal failure patients that not only iron deficiency can be corrected, but also anemia bcz iron deficiency is the most common (even worldwide) cause of anemia in CRF. So if one group the control group gets no iron and the treatment group does get iron in a random group with no one getting extra iron from any other source, its common sense that the treatment team will maintain iron and hgb levels better keeping all variables constant and allowing enough time to pass as we know these patients lose at least 1-2 grams of iron per year.
The real issue is not the study results. This is an answer that doesn't even require a study as long as above items hold true. Real issue is company red tape and internal issues.
So will giving iron to one group and not the other demonstrate a difference over a year's time? That's a no-brainer. Regarding the company management, that's an issue I'm divided on.
Damaged kidneys, as is the case in patients on dialysis, do not produce sufficient levels of erythropoietin; thus the production of red blood cells is severely affected. Even with proper levels of iron in the patients blood stream it does not circumvent the use of ESA, such as Epogen.
Each time a patient is subjected to dialysis, the patient loses more iron from the blood stream. Iron that is currently being used in dialysis patients can cause severe allergic reactions as the molecule size is greater than 45000 daltons in size, causing the body to have an exaggerated response.
RMTI has successfully found a way to replace the lost iron, which is a precursor to red blood cell production in a innovative manner. Patients are administered SFP during dialysis. Patients have dialysis on MWF or TTHSAT, at least 3 days a week, pending they follow their fluid restriction.
ESA in the US is limited to Epogen, marketed by Amgen and accounted for nearly 2 billion dollars in sale last year. The FDA has been closely monitoring ESA usage due to recent allegations of pharmacy kickbacks by Amgen, for which it was fined $24.9 million. ESA drugs are notorious for their unsafe profile and can lead to a significant increase in Hgb and HCT levels causing a myriad of cardiac problems including MI's, CVA, etc.
KERX was able to show a reduction of 25% in ESA use with their iron replacement therapy in their latest clinical data update. If RMTI is able to show an equal or greater reduction, while maintaining Hgb levels, expect the share price to go parabolic. If you consider the fact that:
1. KERX does no sales and has a market cap of $610.43 million with current outstanding shares of 81.72 million and
2. RMTI has a market cap of $142.88 million with current outstanding shares of 37.54 million with sales of 50 million last year.
3. RMTI renegotiated a contract with Davita and signed a contract with Nxstage.
4. Clinical trials have almost ended, so costs will drop and profit increases
SFP iron can be beneficial if bioavailable by:
1. Addressing iron-deficiency (most common cause of anemia - barnone,)
2. Making EPO more effective (hence need for less on a weekly and longer-term basis)
3. It provides an efficient method of continuous iron supplementation so when EPO is given and removes a large portion of iron from the stores for hemoglobin production, that iron is replaced in the body for other uses including constant red blood cell turnover.
4. Decrease need for IV iron administration
5. Perhaps even find a method to be used in other patient populations such as those with inflammatory bowel disease who have poor uptake from the GI tract.
I think SFP can be a great product and based on population data and knowing the most common cause of anemia in the general public and chronic renal failure, it does not take a scientist to know that the CRUISE 1/2 results will be successful. You know iron is needed for red blood cell production. They turnover every 90-120 days. You plan the study for 12 months. You withhold iron supplementation from the controls and give SFP iron to the treatment arm and who is going to do better with all other variables kept constant, of course the SFP group. So people arguing about whether the results will be favorable or not are arguing for no reason as long as everyone in the study gets the same amount of ESA/EPO and external iron.
My only issues are with company long-term management as the issues with FDA and internal issues and lawsuits do not add to stock security and confidence.
I am not disagreeing with the utility of SFP iron as a smart and efficient way of addressing iron concerns in dialysis patients who are prone to iron loss. Instituting SFP iron along with dialysate is a very smart, efficient, and easy method of administration. Most patients have a long-term dialysis catheter or AV-fistula that is used for the nearly every-other day sessions and it beats having to get IV infusions which definitely have side-effects. I can see the SFP as providing a method of stabilizing and maintaining iron levels on a longer basis.
My big point is that while erythropoietin production from the kidneys diminishes in patients with renal failure, at the early stages and even late stages, EPO levels are not always lacking. Usually the first and most overall common reason for anemia is iron-deficiency whether it be from lack of intake/supply, increased loss or lack of a bioavailable form. If your car stops running, you check the most common cause of failure first, not the most obscure cause. In the case of anemia, it is iron deficiency. This is a world-wide proven cause. So you check labs and evaluate the levels of free iron, transferrin, ferritin (long-term iron storage), type of anemia (hypochromic, hyperchromic, microcytic) to make sure that there isn't additional causes for anemia such as folate or B-12 deficiency or chronic inflammation that are causing the anemia before starting EPO from the gate.
My argument (which is positive for SFP iron - IF it is actually bioavailable) is that taking a 100 random people from the country with dialysis-dependent chronic renal disease and anemia (even those without anemia), you are more apt to improve hemoglobin levels by just trying iron supplementation in the majority with addl benefit of low-cost. Additionally, it is those individuals that are iron-deficient that tend to not respond to EPO as well as someone who is healthy. SFP iron is definitely a great method to address the most common reasons for anemia