(Complimentary Newsletter from Target Health Inc.)
Saturday, January 16, 1999
Contents:
1. WHAT'S NEW
2. CELEBREX - THE POLITICS OF
MEDICINE
3. FDA APPROVALS
4. DIABETES AND ASPIRIN
5. MIGRAINE
6. PUBLIC HEALTH
--Immunizations
--Stroke
7. FDA
8. Target Health Inc.
What's New? BACK
TO TOP
This week TARGET HEALTH would like to
welcome R. Zozula (UMDNJ), S. Rauscher, H. Hoag, C. Otley and D. Dillman (ARC-CENTERS) and
J. Raibman (LYONS LAVEY NICKEL SWIFT).
Dr. Jules Mitchel ofTARGET 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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CELEBREX CRISIS -
THE POLITICS OF MEDICINE BACK
TO TOP
The HMO business must realize that without effective, not just cheaper drugs, healthcare costs will never decrease. Pharmaceutical companies do not develop me-to drugs at costs of hundreds of millions of dollars. What they do is develop drugs with unique mechanisms to improve on current therapies. The endoscopic data supporting Celebrex increased ability to reduce GI symptoms is clear. Long-term clinical trials are underway to look at long-term ulcer rates. The following summarizes the positions of several HMOs on the use of Celebrex for their clients. It appears that if the HMO's had their way, they would like to put Celebrex on their formulary when it becomes a generic drug. Any comments?
The United Healthcare Corp. has given Celebrex the lowest reimbursement it offers, while Kaiser Permanente of California is considering not covering Celebrex at all. Two other large insurers, Wellpoint Health Networks Inc. and Aetna U.S. Healthcare, have restricted the use of Celebrex. As a result, arthritis sufferers who want to try Celebrex, a new anti-inflammatory drug that was recently approved by the FDA, may have to pay for the drug themselves.
The reasons for shunning Celebrex appear to be universal. While Aetna and United Healthcare are still reviewing the drug and may change their policies, Wellpoint and Kaiser Permanente both noted that Celebrex is much more expensive than generic brands, regarded by doctors to be equally effective. These early limits on coverage may quickly evolve into a national pattern, which could be financially troublesome for the 13 million Americans who currently take anti-inflammatory drugs like Celebrex. The resistance to cover Celebrex by some insurers comes as a surprise to many in the healthcare industry. Many of the nation's top rheumatologists have heralded Celebrex as a breakthrough, given that some studies suggest the drug is less likely to cause ulcers and gastrointestinal bleeding than many medications.
The problem concerning Celebrex arouse when the data presented to the FDA by SEARLE, Celebrex's manufacturer, and PFIZER, the drug's co-marketer, did not fully convince the FDA about the ability of Celebrex to reduce GI symptoms in comparison with currently marketed NSAID's. As a result, the FDA asked for more long-term studies and required the NSAID class label warning of the risk of gastrointestinal bleeding and ulcers.
Every once in a while there is a new drug approval for an indication for which alternative medications are not available or the alternative medications are not based on modern concepts or technology. TARGET HEALTH is pleased to announce a new drug developed by OTSUKA PHARMACEUTICALS for the treatment of Intermittent claudication.
Intermittent claudication affects several million predominantly elderly Americans. It can greatly impair their ability to walk without considerable discomfort and can seriously affect their ability to exercise or even engage in ordinary activities of daily life. Intermittent claudication results from peripheral arteriosclerotic vascular disease, a condition more commonly known as atherosclerosis or hardening of the arteries. Atherosclerosis occurs when deposits of fatty substances build up, in this case in the legs, leading to an inadequate blood supply to the leg muscles. Standard effective treatments include intensive exercise regimens and drug treatments, i.e., pentoxifylline (Trental). Under certain circumstances, re-vascularization procedures are performed to open the leg arteries or to provide a replacement artery.
FDA has approved Pletal (cilostazol) a new drug for treating stable intermittent claudication. This drug is the first to be approved for this indication in more than 15 years. Pletal has not been evaluated either for safety or effectiveness among patients with more severe peripheral vascular disease who have claudication pain at rest, leg ulcer or gangrene. Pletal was studied in eight clinical trials (most of three to six months duration). In 6 of the 8 studies, patients treated with Pletal (at either 50 or 100 mg taken twice daily) compared to those treated with a placebo, were able to walk further before claudication began and also before the pain became intolerable and forced them to stop walking. Additionally, patients treated with Pletal reported a greater increase in both walking distance and walking speed during daily routines.
Clinical studies in several thousand patients did not identify serious toxicity, but there are two important concerns with the use of Pletal. The first concern is that Pletal is pharmacologically related to a group of drugs studied for heart failure, the phosphodiestrase III inhibitors, several which have shown increased deaths rates in patients with severe heart failure. It is not known what effect these drugs have on people with less severe heart failure or no heart failure. Pletal was studied in about 2100 patients with claudication, many of whom had other conditions such as a history of heart attacks or diabetes, but the patients did not have severe heart failure. In the patients studied there was a low mortality rate, 0.8% in patients treated with Pletal, 0.7% in placebo patients. There was insufficient evidence to determine whether Pletal has an adverse survival effect in patients without heart failure. Labeling will state that Pletal should never be used (is contraindicated) in patients with heart failure. The labeling will also point out that there is insufficient information to determine whether Pletal has an adverse survival effect in patients without heart failure.
The second concern is that Pletal has not been studied in combination with clopidogril, a drug recently approved for use in patients with peripheral vascular disease to reduce the rate of serious events (heart attacks, stroke, and death). Clopidogril was not available while Pletal was being developed, but is potentially important for patients with peripheral vascular disease. Concern arises because both Pletal and clopidogril inhibit platelet function, and it is possible that combined use could lead to excessive bleeding. Pletal was, however, used with aspirin, which also inhibits platelet function, without an apparent adverse interaction.
DIABETES AND ASPIRIN
BACK TO TOP
In comparison to controlled clinical trials, epidemiological studies allow for broad stroke evaluation of data from large numbers of patients. Another approach to evaluate clinical data is to analyze published data across many studies through the use of meta-analyses. TARGET HEALTH specializes in both traditional and meta analyses and has just completed complete data management and analyses for an NDA in the area of fertility.
According to a recent published report in The American Journal of Medicine (Am J Med 1998;105:494-499), the absolute benefit of aspirin therapy in diabetic patients with coronary artery disease is greater than in patients without diabetes. In order to examine the benefits of aspirin therapy, a multicenter team examined outcomes in this patient population over a 5-year period. More than 10,000 patients with and without noninsulin-dependent diabetes mellitus were identified during screening for the Bezafibrate Infarction Prevention Study. More than half of the patients in each group reported that they were on aspirin therapy at baseline. Overall cardiac mortality among diabetic patients treated with aspirin was 10.9% versus 15.9% in the nonaspirin group. The corresponding all-cause mortality rates were 18.4% and 26.2%, respectively. After accounting for possible confounding factors, the hazard ratios for cardiac and all-cause mortality in aspirin users versus nonaspirin users were similar for diabetics and nondiabetics.
Migraines are one of the most debilitating diseases. Since the development of Sumatriptin by GLAXO-WELLCOME, several pharmaceutical companies started development programs. MERCK recently received approval for rizatriptin and other companies such as PFIZER have new products in the pipeline. The following summarizes the results of one of MERCK's supported clinical trials:
According to a report in the November/December issue of Headache, oral rizatriptan appears to provide more rapid relief of migraine pain and related symptoms compared with oral sumatriptan. Rizatriptan is a newly developed 5-HT1B/1D selective receptor agonist. A large number (1,268) of migraine patients were randomized to 5 mg rizatriptan, 10 mg rizatriptan, 100 mg sumatriptan or placebo. All of the subjects were outpatients treated during a single migraine episode. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour. Both agents were significantly superior to placebo. After adjusting for age, it was found that 10 mg rizatriptan had an earlier onset than 100 mg sumatriptan in time to pain relief through 2 hours. The differences between rizatriptan and sumatriptan were reported to be significant and clinically relevant. It was also concluded that the increased efficacy of rizatriptan 10 mg did not appear to be accompanied by an increase in overall side effects relative to sumatriptan 100 mg.
An ounce of prevention is often worth a pound of cure. As part of TARGET HEALTH's ongoing desire to disseminate timely information to our readers (in this case especially to those with children and grandchildren), the following from CDC is being reported:
Childhood Immunizations
CDC made two changes this year in the 1999 childhood immunization schedule. The new schedule is published in the January 15 issue of the Morbidity and Mortality Weekly Report (MMWR). CDC has recommended the use of the inactivated poliovirus (IPV) vaccine for the first two doses, at 2 months and 4 months of age, in the four-dose series. CDC has also recommended that the oral poliovirus (OPV) vaccine be given for the third and fourth doses, at 12 to 18 months and at 4 to 6 years. The CDC no longer recommends the OPV vaccine for the first two doses. For the first time, the CDC has recommended that the new oral rotavirus vaccine be given at 2 months, 4 months and 6 months of age, with the series to be completed before age one. The CDC has alerted healthcare professionals that Merck has discontinued production of the 2.5 g/0.5 mL pediatric dose of Recombivax HB hepatitis B vaccine. The 5 g/0.5 mL dose of the vaccine is now indicated for all vaccinees younger than 19 years of age.
In other changes, the diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) has now been designated as the preferred vaccine formulation for all doses in the immunization series. Finally, CDC has warned that combination vaccines containing Haemophilus influenzae type b (Hib) conjugate vaccine and DTaP are not for use in primary immunization. Use of the combination vaccine is restricted to infants between the ages of 15 and 18 months.
Stroke
In the January issue of Stroke (Stroke 1999;30:1-6.), it was reported that the relative risk of stroke in men who exercised less than one time per week, one time per week, 2 to 4 times per week or five or more times per week were 1.0, 0.79, 0.80 and 0.79, respectively. Men who exercised vigorously once per week experienced a 21% lower risk of total stroke than those who did so less frequently. The study evaluated exercise and stroke risk in more than 21,800 male physicians during more than 11 years of follow-up. Subjects had been randomized to receive aspirin alone, beta-carotene alone, aspirin plus beta- carotene or placebo. Age range was 40 to 84 years of age. The benefits of exercise on stroke risk appear to be mediated through lower body mass index, improved glucose tolerance, lower blood pressure and lower cholesterol levels.
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.
FDA approved 39 new drugs last year and the pharmaceutical industry will increase R&D investment to a record $24 billion in 1999. Research-based pharmaceutical companies pour back more than 20% of sales into R&D, a higher percentage than virtually any other industry. The pharmaceutical industry's ratio of R&D to sales is more than five times that of the aerospace industry.
Among the drugs brought to market in 1998 are:
a. A new AIDS medicine requiring only once-daily
dosing, which will simplify the complex drug regimen and enable more patients to follow
it.
b. The first medicine to treat Crohn's disease, a debilitating
gastrointestinal disorder.
c. The first new tuberculosis drug in 25 years, which offers a shorter
course of treatment and may help combat the problem of drug resistance.
d. Three new medicines for rheumatoid arthritis, which afflicts more than
2 million Americans.
e. Two new medicines for breast cancer, which affects 1 out of 10
American women.
f. A breakthrough drug for erectile dysfunction, a problem for an
estimated 30 million American men.
The drugs approved by the FDA in 1998 were reviewed in an average time of 11.7 months, compared to 16.2 months in 1997. The faster review times can be attributed to stricter FDA requirements for complete NDA submissions and to the availability of the user fees paid by pharmaceutical companies to enable the FDA to hire additional reviewers. Before user fees were established, it took the FDA an average of 30 months to review a new drug application. In the 1990s, the FDA approved 338 new drugs.
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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