(Complimentary Newsletter from Target Health Inc.)
Saturday, January 2, 1999
Contents:
1. WHAT'S NEW
2. NATURAL PRODUCTS AND ALTERNATIVE
MEDICINE
3. APPROVALS AND AGREEMENTS
--Celebrex (Searle)
--Modafinil (Cephalon)
--Levaquin (Ortho McNeil)
--Otsuka and Pharmacia & Upjohn
4. FDA
--Y2K
5. Target Health Inc.
What's New? BACK
TO TOP
This week TARGET HEALTH would like to
welcome A. Tano (OTSUKA PHARMACEUTICALS), I. Goldstein (BOSTON U. SCHOOL OF
MEDICINE), T. Wakefield, Dan Myers and P. Andrews (U. MICHIGAN SCHOOL OF MEDICINE.)
M. Padval (PRIMEDICA) and W. Burke (ERNST & YOUNG).
Our friend and colleague Dr. Joe Lombardino has retired after over 40 years at PFIZER. Dr. Lombardino was one of the discoverers of FELDENE, PFIZER's breakthrough NSAID for the treatment of rheumatoid arthritis and osteoarthritis. There are few in the pharmaceutical industry who can match Dr. Lombardino in terms of courage, persistence and high ethical standards. TARGET HEALTH wishes Dr. Lombardino success in his new endeavors.
Dr. Jules Mitchel of TARGET HEALTH will be lecturing on February 2, 1999 at the 14th Annual Dermatologic Conference on Insights into Evolving Issues in Dermatology at the Robert Wood Johnson Medical School. The topic will be Regulatory Aspects of Product Development. Dr. Mitchel will be joined by colleagues Ron Trancik (PHARMACIA & UPJOHN), Doug Canfield (CANFIELD SCIENTIFIC) and Otto Mills (UMDNJ). For more information please contact Dr. Mitchel at TARGET HEALTH.
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NATURAL PRODUCTS
AND ALTERNATIVE MEDICINE BACK
TO TOP
While Natural Products and Alternative Medicine are here to stay, these treatments and therapies are not as rigorously tested as those in traditional Western medicine. The FDA's powers to regulate in these areas need to be strengthened and reporting of adverse events expanded. The FDA does have a website for Natural Product adverse event reporting and one would be amazed as to its content. For more information, please contact TARGET HEALTH.
Natural Products
A report of an active compound in green tea, epigallocatechin gallate (EGCg), which in vitro inhibits the growth protein of cancer cells, was presented at the 38th American Society for Cell Biology meeting in San Francisco. EGCg inhibits the overactive form of quinol oxidase (tNOX) on the surface of cancer cells without inhibiting the function of normal quinol oxidase (NOX) in cell division. In testing the effects of various compounds on tNOX, it was found that infusions of black tea inhibited tNOX at dilutions of 1:10. Similar testing of green tea showed tNOX inhibition at dilutions of 1:100 to 1:1000, which suggested that green tea is rich in some substance that inhibits the enzyme. In vitro studies of mammary carcinoma cells showed that EGCg inhibited growth of cancer cells and induced apoptosis. EGCg did not kill normal mammary gland cells and cervical carcinoma cells reacted the same to EGCg as did mammary carcinoma cells. In the presence of EGCg, the cancer cells literally failed to grow or enlarge after division.
Alternative Medicine
Based on a recently publish survey (Int J Risk Safety Med 1998:11;99-106), it has suggested that complementary and alternative medicines may cause a much higher incidence of adverse reactions than previously suspected. The warning follows a survey of 1,521 family physicians. Of 686 physicians who replied to the survey, 78 (11%) submitted 96 separate reports of suspected adverse events which were judged to be serious. The survey identified spinal manipulation as the most common cause of serious adverse events. Other specific events identified were associated with acupuncture (hepatitis B, pneumothorax and a lodged broken needle), aromatherapy (allergic reaction and cardiac arrhythmia) and hypnotherapy (severe hallucination and emotional distress).
APPROVALS AND AGREEMENTS
BACK TO TOP
TARGET HEALTH is committed to getting products to the market place and works closely with sponsors and the FDA to make it all happen. Another IND has just been tentatively approved in the Division of Reproductive Drugs and the recently submitted NDA is under active review..
Celebrex
In the US, more than three million suffer with rheumatoid arthritis (RA) and 16 million more with osteoarthritis (OA). Both diseases cause painful inflammation and joint deterioration. The FDA has just approved Celebrex (celecoxib) for the treatment of RA and OA. Celebrex is an NSAID that blocks production of prostaglandins by inhibiting the enzyme cyclooxygenase-2 (Cox-2). Unlike other NSAIDS, Celebrex does not inhibit the enzyme cyclooxygenase-1 or COX-1. Inhibition of COX-1 is believed to contribute to some of the adverse effects of NSAIDS, including upper gastrointestinal ulcers. It is therefore hoped that Celebrex will have safety advantages compared to other NSAID products. Additional studies and post-marketing experience will add substantially to the understanding of how the overall risks and benefits of Celebrex compare with those of other NSAID products.
Celebrex was found to be an effective arthritis treatment in placebo and active-controlled clinical trials that enrolled 2100 patients with rheumatoid arthritis and 4200 patients with osteoarthritis. Celebrex was compared to other NSAID products in several of these clinical trials by using endoscopy to determine the incidence of stomach and upper intestinal ulcerations. In these studies, it was showed that patients taking Celebrex had a substantially lower risk of ulcers detected by endoscopy over the study period of 12 to 24 weeks when compared to patients who took other NSAIDS.
However, according to the FDA, since NSAID products can cause a range of gastrointestinal problems, and patients with endoscopic ulcers may often recover without special treatment and without experiencing any serious symptoms or complications, additional studies in many thousands of patients would be needed to see whether Celebrex actually causes fewer serious gastrointestinal complications than other NSAID products. Until such studies are done, the drug labeling for Celebrex will include the standard warning for doctors and their patients about the risks associated with all NSAIDS, including risks of GI ulceration, bleeding and perforation. The labeling advises patients taking these drugs to be alert for ulceration and bleeding that can occur with or without warning. Patients should promptly report signs and symptoms of gastrointestinal ulceration or bleeding, skin rash, unexplained weight gain, or swelling to their physicians.
In addition, Celebrex does not affect platelet aggregation (clumping) an important part of the blood clotting process. Many other NSAID products can interfere with this platelet function, which may increase the risk of bleeding complications in some patients. However, Celebrex does not appear to be different from other NSAIDS in its effects on the kidneys. Celebrex is manufactured by SEARLE and will be co-marketed with PFIZER.
Modafinil
TARGET HEALTH is sure that our friend and colleague, Dr. James Cappola (CEPHALON) is pleased with the good news from FDA this month that CEPHALON received approval of modafinil (Provigil), the first nonamphetamine approved for the treatment of narcolepsy. FDA granted approval based on results of two phase III trials that involved more than 550 patients with narcolepsy who received either modafinil or placebo. Modafinil appears to lack the adverse effects often seen with amphetamines, such as jitteriness, anxiety and heart palpitations. Modanafil also does not cause hepatotoxicity, which can occur with amphetamine use. According to CEPHALON, 5% of the clinical trial patients had to discontinue therapy due to adverse events. However, most of the adverse events, which included headache, infection, nausea, nervousness, anxiety and insomnia, were mild to moderate in severity.
The FDA approval is for the once-daily 200 mg dose of modafinil and it is expected to be classified as a Schedule IV controlled substance. A Schedule IV drug is one that has a low potential for abuse relative to the drugs or other substances in Schedule III, which are drugs that might lead to moderate or low physical dependence or high psychological dependence. Other Schedule IV drugs include Xanax and Valium. Possible off-label uses of modafinil may include treatment of excessive daytime sleepiness and other symptoms of sleep disorders.
Levaquin
Levaquin (levofloxacin tablets/injection), a leading prescription antimicrobial, has received FDA approval for the treatment of uncomplicated urinary tract infection, a condition affecting one in five U.S. women. The new indication is for short-course therapy with Levaquin once-daily for three days in the treatment of mild to moderate uncomplicated urinary tract infection (acute cystitis) in women, caused by the organisms Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus. Since its U.S. introduction in 1996, Levaquin has gained widespread use in the treatment of adults with mild to moderate complicated urinary tract infections and acute pyelonephritis, as well as community-acquired pneumonia, acute maxillary sinusitis and acute exacerbation of chronic bronchitis.
Levaquin was studied for the treatment of urinary tract infection in a double- blind multicenter trial, in which 545 subjects were assigned randomly to three days of levofloxacin 250 mg once-daily or ofloxacin tablets/I.V. 200 mg twice- daily. Ninety six percent of all pathogens were eradicated in the levofloxacin group, compared with 95% for ofloxacin. Symptoms were cured or improved in 98% of patients receiving levofloxacin, and in 97% of those receiving ofloxacin. Drug-related side effects occurred in 3.4% of subjects receiving levofloxacin and in 7.5% of those receiving ofloxacin.
Otsuka and Pharmacia & Upjohn
PHARMACIA & UPJOHN announced the signing of a binding letter-of-intent to co- promote Pletal Tablets (cilostazol) in the US with OTSUKA AMERICA PHARMACEUTICALS. Pletal is currently under FDA review for the treatment of symptoms associated with intermittent claudication, a symptom of peripheral arterial disease that occurs in the lower extremities. In addition to the U.S., the agreement also provides PHARMACIA & UPJOHN with exclusive marketing rights to Pletal in Canada and possibly other markets as agreed by the two companies
TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients and FDA. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available. For additional information, please contact Dr. Jules T. Mitchel at TARGET HEALTH.
Y2K
The Federal Government has established a World Wide Web site to provide information on the "Year 2000" status of medical devices and scientific laboratory equipment (biomedical equipment). There is a chance some of these products will experience problems associated with the use of date information on January 1, 2000 if the computer systems, software applications or imbedded chips used in these devices and equipment contain two-digit fields for representation of the year. In such a circumstance, the software program will not be able to distinguish the year 2000 from the year 1900. When the device needs to calculate a date to work, this can potentially lead to the product failing to function as expected. Analysis of the year 2000 problem shows the most likely errors will result in printed test results that are incorrectly dated or self evidently wrong but some may more directly put patients at risk.
The website, administered by the FDA for the government's Chief Information Officers Council Subcommittee on the Year 2000, is intended to give product users in healthcare facilities and research laboratories and other interested parties one comprehensive resource for information about the "Year 2000 compliance" of biomedical equipment. "Year 2000 compliance" means that the product accurately processes and stores date and time data during, from, into and between the 20th and 21st centuries, and the years 1999 and 2000. (Processing and storing data may include calculating, comparing, displaying, recording and sequencing operations involving date and time data, including correct processing of leap year data.) To be Year 2000 compliant, products must function as intended or expected, regardless of the date.
Should they not be corrected in time, Year 2000 date problems potentially could pose serious health and safety consequences. A medical device function which depends on a calculation involving a date and which is performed incorrectly as a result of a date problem could lead to a risk to the patient. One example is a product used for planning the delivery of radiation treatment using an radioactive isotope as the radiation source. An error in the calculation of the radiation source strength on the day the therapy is to be delivered could result in an incorrect treatment and have adverse consequences for the patient. For more information, please contact Dr. Jules Mitchel at TARGET HEALTH.
TARGET HEALTH INC. is a full service CRO with staff dedicated to all aspects of Regulatory Affairs, Clinical Research, Biostatistics, Data Management, Strategic Planning and Drug and Device Development. TARGET HEALTH also has a group of specialized advisors in the areas of Toxicology, Analytical Methods Validation, Product and Process Development, Quality Assurance, Manufacturing and Animal Health.
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