ITP Treatments

Platelet Growth Factors ( TPO Receptor Agonists)

Platelet Growth Factors or Thrombopoietin (TPO) receptor agonists are a class of treatments that stimulate the bone marrow to produce more platelets. TPO, a protein made in the liver, naturally stimulates platelet production in the bone marrow. TPO receptor agonists bind to the same receptor as the TPO produced in the body. This prompts the megakaryocytes in the bone marrow to produce more platelets.

While ITP is often considered a disease characterized by platelet destruction, recent research has shown that many people with ITP also have unusually low platelet production. The additional bone marrow stimulation prompted by the TPO receptor agonists creates a sufficient number of platelets to overcome the platelet destruction or platelet production problems in most people who receive these treatments.

romiplostim (NPlate) - Amgen

Romiplostim is a manufactured peptibody (part peptide and part antibody) liquid that is given by weekly subcutaneous (under the skin) injection. On September 4, 2008, the US FDA approved romiplostim for adults with ITP (either splenectomized or not) who have failed at least one other treatment for the disease. Approval in other countries is expected in 2009.

Dose: The dose of romiplostim depends on the patient's weight and response to previous doses. The initial dose is 1 mcg/kg. The dose is reduced or discontinued if the platelet count rises too high or the patient doesn't respond.

Side Effects: The most common adverse reactions are joint and muscle pain, dizziness, insomnia, indigestion, and 'pins and needles' sensation. There is a potential for patients to develop reticulum (fibrous growths) in the bone marrow and also for the platelet count to drop below the pre-treatment count if the treatment is discontinued.

Risk Program: The FDA has mandated that romiplostim be available only through a risk assessment program (NEXUS) that includes physician and patient education and enrollment.

Assistance Programs: Amgen has established several programs to assist those people who are not insured, underinsured or who cannot meet the insurance co-payments.

Related Web Sites:

www.nplate.com
/www.fda.gov/cder/foi/label/2008/125268lbl.pdf

eltrombopag (Promacta) - GlaxoSmithKline

Eltrobopag is a small molecule (pill) taken daily.  On May 30, 2008, the FDA committee responsible for reviewing the clinical trial results recommended approval of eltrombopag by a vote of 16 to 0.  The drug is currently awaiting final approval by the FDA for the short term (6 week) treatment of ITP in adults.

Dose: In the clinical trials, patients were given various does of eltrombopag for six weeks.  The patients receiving 50 mcg or 75 mcg tablets had the best response.  Longer term clinical trials are in progress.  The pill must be taken on an empty stomach as other medications and food affect its absorption.

Side Effects:  The most common adverse reaction was a mild to moderate headache.  Elevated liver functions was present in some research subjects. Cataracts were observed in mice, but not in people.   As with other treatments in this class, the FDA is concerned about the development of reticulum and a drop in platelet count after stopping the drug. 

Risk Program: The FDA is requiring that a risk assessment program accompany eltrombopag approval. 

Assistance Program: Information on any company sponsored assistance program for eltrombopag will be available upon final FDA approval.

Related Web Sites:

/www.fda.gov/ohrms/dockets/ac/08/slides/2008-4366s1-02-GSK-corepresentation.pdfwww.fda.gov/ohrms/dockets/ac/08/minutes/2008-4366m1-Final.pdf

AKR501 – Eisai

AKR501 is a small molecule (once daily pill) that has stimulated platelet production in mice and healthy human subjects.  This compound was recently acquired by Eisai from MGIpharma, and previously, AKArx. A clinical trial for ITP patients is in progress. 

See www.clinicaltrials.gov/ct2/show/NCT00441090 for information on participating in the clinical trial.

LGD4665 – Ligand Pharmaceuticals

Ligand Pharmaceuticals is recruiting ITP patients for a six week clinical trial for this once daily pill.  This compound has increased the platelet counts and had an good safety profile in mice and healthy human subjects.

See http://www.clinicaltrials.gov/ct2/show/NCT00621894 for information on participating in the clinical trial