- Eltrombopag Shows Promise in Early Studies
- Preventing Glucocorticoid-Induced Bone Thinning
- Two ITP Drugs Moving Forward
- Privigen Stabilizer Passes Test
- Rigel Says R788 Passes Phase 2 Safety Study
- New Law Gives FDA More Authority Over Drug Safety
- Researchers Watch New Platelets Form
- Study Shows Stress Harms Health
- Vitamin D Protects DNA and Lowers Inflammation
- Exercise Reduces Fatigue
- Health Info via Cell phones
(Note: There was much ITP news presented at the recent American Society of Hematology meeting. We will send a special e-mail with some of the findings. See http://www.hematology.org for more information)
ELTROMBOPAG SHOWS PROMISE IN EARLY STUDIES
Two studies of eltrombopag, a small molecule that binds to the thrombopoietin receptor on megakaryocytes to spur platelet production (called a TPO mimetic), suggest the oral compound can increase platelet counts. The first study, from Cornell Weill Medical Center, was a phase 1, placebo-controlled trial of eltrombopag at 3 different dose levels for people with ITP. The two higher dosages raised platelet counts and decreased bleeding. The second study, from Duke University, tested the drug for thrombocytopenia with cirrhosis due to hepatitis C infection. Platelet counts rose with the drug, enabling initiation of antiviral therapy. But questions remain.
Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007;357:2237-2247.
McHutchison JG, Dusheiko G, Shiffman ML, et al. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med. 2007;357:2227-2236. [Editorial pg. 2299]
PREVENTING GLUCOCORTICOID-INDUCED BONE THINNING
Patients with ITP often take glucocorticoids, such as prednisone, to suppress the immune system and block platelet destruction. But a major adverse event is osteoporosis, or thinning of the bones, that increases risk fracture. Patients are usually treated with bisphosphonates, such as alendronate. A study from Alabama suggests that another drug, teriparatide, may work just as well or better for patients with the most severe bone loss. A separate article in the same issue noted that quinolones, a type of antibiotic, may increase risk for tendon injury, more so in the elderly and persons taking corticosteroids.
Saag KC, Shane E, Boonen S, Marin F, Donley DW, Taylor KA, Dalsky GP, Marcus R. Teriparatide or Alendronate in Glucocorticoid-Induced Osteoporosis. N Engl J Med. 2007;357:2028-2039. [Editorial pg. 2084]
Sambrook PN. Anabolic Therapy in Glucocorticoid-Induced Osteoporosis. N Engl J Med. 2007;357:2085-2086.
TWO ITP DRUGS MOVING FORWARD
Ligand Pharmaceuticals (San Diego) has completed a Phase 1 dose-escalation study of its small molecule, non-peptide TPO mimetic, called LGD-4665. Its partner, GlaxoSmithKline, reported it will submit a new drug application to the FDA for eltrombopag (Promacta), another TPO mimetic, by year’s end for treatment of short-term ITP.
PRIVIGEN STABILIZER PASSES TEST
CSL Behring (Bern, Switzerland) announced that a stabilizer used in Privigen, the company’s immune globulin intravenous liquid does not cause neurological problems, as has been reported for a different stabilizer. The stabilizer in Privigen, L-proline, is a natural amino acid the enables Privigen to be stored at room temperature up to three years. The FDA approved Privigen in July 2007 for treatment of ITP. It will be available in first quarter 2008.
RIGEL SAYS R788 PASSES PHASE 2 SAFETY STUDY
Rigel Pharmaceuticals reported its phase 2 study of R788, the oral Syk kinase inhibitor, improved platelet counts in patients with ITP for whom other treatments had failed. Primary side effects were gastrointestinal.
NEW LAW GIVES FDA MORE AUTHORITY OVER DRUG SAFETY
President Bush signed a new law in September to overhaul FDA monitoring of drug safety. The main improvement, according to its proponents, is that drug makers will now be required to post all their clinical trial results for marketed drugs in an NIH-supported database [clinicaltrials.gov]. It also gives FDA power to demand clinical trials on marketed drugs, fine companies for noncompliance, and establish a database of electronic medical records of 100 million people so that experts can look for emerging problems with drug safety. The law is in response to a rash of safety issues that have surfaced in the past few years.
Wadman M. New Law Gives FDA More Influence To Monitor Drug Safety. Nature Medicine. November 2007; 13(11):1269.
RESEARCHERS WATCH PLATELETS FORM
Harvard-based scientists used special microscopy to watch how platelets are generated in the bone marrow of mice. Megakaryocytes in the bone marrow are the source of platelets. Their images showed that when blood flows through the microvessels in the marrow, so-called “proplatelets” are sheared off of the megakaryocytes and sent into the blood stream.
Junt T, Schulze H, Chen Z, Massberg S, Goerge T, Krueger A, Wagner DD, Graf T, Italiano JE, Shivdasani RA, von Andrian UH. Dynamic Visualization of Thrombopoiesis Within Bone Marrow. Science. September 21, 2007;317(5845):1767-1770.
STUDY SHOWS STRESS HARMS HEALTH
Chronic stress has been linked with elevated IL-6 (interleukin-6, a particular cytokine), an inflammatory marker, according to findings of the Multi-Ethnic Study of Atherosclerosis (MESA), a large cross-sectional study. The MESA study, with 6,814 participants, measured the inflammatory markers: C-reactive protein, IL-6, and fibrinogen. The study found elevated IL-6 concentrations in subjects with higher levels of chronic stress. The study’s lead author, Dr. Nalini Ranjit (University of Michigan), said “…problems of psychosocial stress and lifestyle risk factors—particularly obesity—should be considered together during management of CVD (cardiovascular disease) and other inflammation-related chronic disorders.”
Ranjit N, Diez-Roux AV, Shea S, et al. Psychosocial factors and inflammation in the Multi-Ethnic Study of Atherosclerosis. Arch Intern Med 2007; 167:174-181.
VITAMIN D PROTECTS DNA AND LOWERS INFLAMMATION
Vitamin D may reduce risk for aging and inflammation-related diseases by protecting the ends of chromosomes, according to a British study of more than 2,000 women. Poor vitamin D status is associated with increased risks for diseases involving inflammation, including multiple sclerosis, rheumatoid arthritis, and type 1 diabetes. One marker of chronic inflammation and aging is decreased length of telomeres, the ends of chromosomes that keep the DNA on the chromosome stable. The researchers measured blood levels of vitamin D and the length of the telomeres of white blood cells and found that women with higher vitamin D levels had longer telomeres—evidence that optimal vitamin D status may provide a benefit during the aging process.
Richards JB, Valdes AM, Gardner JP, et al. Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women. American Journal of Clinical Nutrition November 2007;86:1420–25.
EXERCISE REDUCES FATIGUE
Physical activity can reduce fatigue among cancer patients, according to a review of 17 studies. The study was specific to cancer-related fatigue, but people with ITP are known to experience fatigue as well. Studies of cancer patients indicate that exercise can reduce fatigue by improving heart and lung fitness and muscle strength.
Medscape, November 2, 2007.
HEALTH INFO VIA CELLPHONES
Health providers and insurance companies are beginning to offer reminders and other health information via text messaging on cell phones. One service, via Intelecare Compliance Solutions in New Haven, CT, offers reminders to take pills, refill prescriptions, take vital signs, or keep appointments.
Zimmerman, R. Don’t 4Get Ur Pills: Text Messaging for Health. The Wall Street Journal, November 20, 2007, Page D1.