Zestoretic

More than half of all PBMs' prescription drug expenditures are represented by nine therapeutic categories, and DCMR has been tracking these average expenditures by category on a quarterly basis for three full years. As of the first quarter of 2003, these nine categories represent almost 56% of PBMs' drug expenditures, with psychiatric drugs the persistent leader at 11.67%. Ulcer/GERD drugs follow, representing more than 9% of all PBM drug costs, and cholesterol drugs represent almost 8%.

It is important to evaluate drug expenditures by therapeutic category, as each class is vulnerable to different market influences. Today's top cost-control strategies for the drug benefit--generic substitution, member copays, prior authorization, step therapy and rebate opportunities--have varying potential for success in different therapeutic categories. In addition, some of these therapeutic categories are also being targeted by specialty pharmacy products--such as biologicals and injectables--which are much more expensive to make, deliver and administer.

These data were originally collected to allow individual health plans and PBMs to compare their costs to a national average. This is even more relevant now, because the data appear to reflect the impact of major events on drug benefit costs--events such as OTC and generic availability of leading products, and changes in national guidelines for diagnosis and treatment.

Drug Makers Vie for Claritin's Abandoned Rx Share

The big news in the allergy and asthma category over the past 12 months has been the OTC availability of non-sedating antihistamines (NSAs)--the class of products that has driven drug costs in the allergy arena for the past decade. OTC availability of Claritin allowed payers to place the remaining Rx NSAs at the highest copay level, and in some cases to require a trial of OTC Claritin before covering Allegra, Zyrtec or Clarinex. Even payers that did not take this aggressive stance could potentially gain negotiating power and anticipate better pricing from manufacturers.

Despite this undeniable opportunity for payers, allergy drug costs continue to represent more than 4% of total drug costs as of the first quarter of 2003--even before the spring allergy season kicked in. The manufacturers of Allegra, Zyrtec and Clarinex have not let up on the DTC advertising campaigns, and they believe they have strong consumer loyalty for their brands.

And now consumers are being bombarded with ads for a different type of allergy treatment--nasal sprays such as Flonase, Nasacort, Nasonex, Rhinocort and Vancenase. They have hit the airwaves with information for consumers about their superior effectiveness and safety--and it's all true. The steroidal action of these sprays is highly effective in controlling nasal allergy symptoms, particularly congestion, and has been proven in many studies to be safe and non-sedating because they are not systemic.

GlaxoSmithKline has an ad campaign that directly suggests consumers who are unhappy their insurance no longer covers Claritin should switch to Flonase. Payers are backing this effort. Flonase has preferred brand status on many MCO formularies, including those of Aetna, Anthem and CIGNA. And WellPoint has included a trial of Flonase in its step-therapy protocol for allergies.

Step therapy and prior authorizations are being aggressively implemented for allergy drugs. This is not only to deter utilization of Rx NSAs, but also to combat the latest threat to MCOs' allergy budget--Singulair. Merck's popular asthma drug product was approved in January 2003 for controlling allergy symptoms, and now the company is promoting it heavily for that purpose. Singulair is a leukotriene receptor antagonist that is steroid-free and has convenient once-daily dosing.

Other drugs in that class, such as Accolate and Zyflo, could potentially benefit from off-label use for this new indication. The allergy drug market in the U.S. is about 50 million people, compared with only 17 million for asthma. Merck anticipates Singulair sales will increase by 53% in 2003.

Singulair may be more effective at controlling congestion and stuffiness in some patients than are traditional NSAs. And it is safe and convenient for use in children. However, Singulair costs around $78 per month retail, compared with $56 per month for Flonase, so WellPoint is requiring a trial of both Flonase and Claritin before covering Singulair for allergy use.

On the horizon, Genentech's Xolair is under review at FDA for treatment of allergic asthma, with a decision expected this month. Xolair, which works by inhibiting immunoglobulin epsilon (IgE), is a first-in-class product that is viewed as a significant clinical advancement by the Asthma and Allergy Foundation of America. Xolair is administered by injection once or twice a month, and the most optimistic analysts predict it will generate annual sales of $750 million by 2008.

New Cholesterol Guidelines Costly to PBMs

In June 2001, new government guidelines tripled the number of Americans who are candidates for drug therapy to lower their cholesterol. We speculate that this factor is at least partially responsible for the fairly dramatic increase in PBM expenditures on cholesterol drugs. According to Medco Health Solutions' 2003 Drug Trend Report, spending on cholesterol-lowering drug products rose 14% during 2002 for Medco clients.

Lipid-lowering agents are the third largest category of prescription drug expenditures. Products driving costs in this therapeutic class are Lipitor, Zocor and Pravachol. These products are all still a couple years away from generic competition, and new products continue to be introduced.

Zetia, marketed by Schering-Plough and Merck, was approved in October 2002, but is not yet available on most health plan formularies. AstraZeneca's Crestor has still not been approved in the U.S., but the manufacturer has been participating in one study after another to demonstrate its effectiveness against competing statins. An FDA panel is scheduled to review Crestor in July.

Diabetes--Well-Managed but Underdiagnosed

Diabetes is approaching epidemic proportions in the U.S., affecting 17 million people and killing 200,000 per year. A person with diabetes averaged $13,243 in 2002 health care costs, compared with $2,560 for a non-diabetic person, according to the American Diabetes Association. Direct medical costs for the U.S. are pegged at $91.8 billion in 2002.

Of those direct medical costs, we estimate that only about 5% are represented by PBM-covered drug expenditures for diabetes. Prescription drug products for diabetes include Avandia, Actos, Avandamet and others. There is some opportunity for generic substitution now that Glucophage and Glucotrol are generically available. Express Scripts has been making aggressive efforts to increase utilization of generic Glucophage.

Given the high prices of some of these products (ranging from $75 to $160/30) and the high incidence of diabetes, we would expect PBM costs in this area to be even higher than they are. Unfortunately, diabetes is not a problem that is easily solved with a pill. Lifestyle modifications and monitoring of blood glucose levels are imperative to success for most patients. The "hands-on" care required to treat diabetes is a significant part of the costs. Most major payers, including those with their own PBM operations--such as Aetna, Anthem, CIGNA and PacifiCare--are using disease management programs for diabetes (figure 2).

In the near future, MCOs are likely to increase preventive programs for diabetes, in alignment with the government's goal to put America on a diet. Diabetes is one of the most common and dire consequences of obesity. Government data show that national obesity costs are comparable to those of smoking, and that overweight children are increasingly being diagnosed with Type 2 diabetes. HHS Secretary Tommy Thompson has called for both insurance companies and restaurants to make efforts toward preventing and reducing obesity.

Approximately six million people are believed to have undiagnosed diabetes, so widespread screening efforts could potentially increase the market for diabetes drugs.

Prescribers Respond to New Hypertension Care Guidelines

A variety of medications are prescribed to control blood pressure, although a third of all patients fail to adequately lower their blood pressure. Medications in this therapeutic category include: diuretics, angiotensin converting enzyme (ACE) inhibitors, beta-blockers, alpha-blockers and calcium channel blockers.

In December 2002, a government-sponsored study concluded that diuretics--the oldest and cheapest alternative --should be the first line of therapy for hypertension. Our data show a dip in PBM costs for hypertension products in the first quarter of 2003. The ALLHAT study was widely publicized, so it is possible that it has had an impact on physician prescribing during this quarter, and that our data reflect this.

In May 2003, the National Heart, Lung and Blood Institute released new blood pressure guidelines that increased the number of Americans with hypertension by 45 million. This almost doubles the U.S. market--to 95 million--for anti-hypertensive drug products. The new guidelines also encourage wider use of drug therapy for controlling hypertension. For this reason, any gains made by increased utilization of diuretics may be offset in the future by increased diagnosis of hypertension.

Generic versions of many popular blood pressure drugs are beginning to be available, and this is a boon to payers. Express Scripts believes there will be significant opportunity for generic substitution of ACE inhibitors Accupril and Monopril starting this year. Lisinopril, sold under brand names Zestril/Zestoretic and Prinivil/ Prinzide, has been available generically since July 2002, and this is another factor contributing to reduce costs. Medco Health Solutions speculated that generic substitution of lisinopril would save its clients and members more than $100 million this year.

However, experts agree that most patients require more than one product for optimum control of hypertension. In fact, a report in the May 21, 2003, issue of the Journal of the American Medical Association finds that single-drug therapy is no more effective at lowering blood pressure than are simple dietary changes.

And because hypertension therapy is individual, payers are reluctant to institute widespread policies such as forcing a trial of diuretics. Therapeutic substitution to direct utilization toward generic products is also more difficult in this category because of the highly individual patient response.

And in response to the ALLHAT study, makers of the higher-cost hypertension drugs have ramped up promotion efforts. Armed with clinical data, sales reps are hitting the streets to convince doctors their products are better than a simple diuretic. Calcium channel blockers such as Cardizem and Norvasc are competing for the title of "most effective in controlling hypertension in African-American populations."

Last fall, Pharmacia won approval for a new product, Inspra (eplerenone), which does not yet appear on most national health plan formularies.

QL for Migraine Drugs

PBMs are spending 2% of their total drug expenditure on migraine medications, primarily Imitrex and Zomig. Other brands available to treat migraine include Amerge, Axert, Cafergot, DHE 45, Ergomar, Migranal, Migralam, Maxalt and Sansert.

The National Headache Foundation believes that 28 million Americans suffer from migraine, and spend about $4 billion a year on mediations to stop migraine pain. We estimate that PBMs are spending almost $2 billion a year on migraine-specific drugs such as Imitrex. Some portion of the NSAIDs cost category can also be attributed to migraines.

A majority of health plan formularies specify quantity limits for migraine medications. Because Imitrex comes in injection, pill, and nasal spray forms, quantity limits must be set for each dosage form. Typical limits are four injection kits, 20 pills, or six nasal sprays per 20-to-35-day prescription period.

DTC Still Drives Cox-2s

Non-steroidal anti-inflammatory drugs (NSAIDs) represent 5.92% of total drug costs today, and this percentage is increasing at a faster pace than are the other categories. The Cox-2 inhibitors, a relatively new class of brand-name medications prescribed to treat the pain and inflammation of osteoarthritis, primarily drive costs in this category. We estimate that about 68% of expenditures in the NSAIDs category can be attributed to Cox-2 drugs, primarily Celebrex and Vioxx.

Cox-2 inhibitors cost around $750 per patient per year. Alternatives abound for treatment of osteoarthritis, including some very low-cost generic Rx products and OTC products.

Other markets for these drugs include rheumatoid arthritis and severe menstrual cramping, but osteoarthritis is the primary target of these products, which are heavily advertised to consumers. In October 2002, the Centers for Disease Control and Prevention released a new estimate that 70 million people--a third of all adults--suffer from arthritis or joint pain. This estimate was revised up from 43 million.

Cox-2 brands are Celebrex, Vioxx, and the latest entry, Bextra. When Pharmacia/Pfizer introduced Bextra in March 2002, payers had reason to hope that the added competition would increase their negotiating power in this drug class. However, Bextra is made by Pfizer/ Pharmacia, the same company that makes Celebrex, so it doesn't really add another player to the game. In addition, Bextra's launch was followed by reports of serious adverse effects that prompted labeling changes.

Nevertheless, Bextra has made it onto the national formularies of most major payers, along with Celebrex and Vioxx. In addition to the cost issues, Cox-2s have been associated with an increased risk of cardiac problems. So most plans have instituted an across-the-board prior authorization requirement for Cox-2 drugs.

Aggressive drug cost management programs advocate a step-therapy approach to treating osteoarthritis pain. Many formularies specify a trial of OTC and generic Rx NSAIDs and/or a documented risk of gastrointestinal bleeding.

Arthritis (all types) is the number one cause of disability in the U.S., and is only going to become a bigger problem for payers in the next several years, due to our aging demographics and our culture of demand. Patients with severe arthritis that is not relieved by oral prescription medications are beginning to demand services that are more expensive than any pill. Available therapies include physician-administered injections of corticosteroids, biological products such as Enbrel, Remicade and Synvisc, and surgical procedures such as knee replacements.

On the horizon, drug makers around the globe are frantically working on a next generation of Cox-2 drugs that combine other types of action to allay the gastrointestinal risks while maintaining the effectiveness of today's products. But conditions will have to be extremely favorable for new rival products to be launched in the U.S. Merck (maker of Vioxx) withdrew an application for its new drug, Arcoxia, until such time as it can win approval for a broad range of indications.

Psychiatric Drugs--Largest Category for Adults and Children

Psychiatric drugs are far and above the largest category of costs for PBMs. In part, this is due to the chronic or long-term nature of psychiatric complaints, the devastating effects of untreated psychiatric symptoms, and major clinical advances that have resulted in many high-cost new drug products over the last decade.

Another reason costs are so high in this category is because the psychiatric drug category is large and loosely defined. For most of the PBMs surveyed, it encompasses any product that acts on the central nervous system and/or is related to any type of behavior, mood or brain functioning. This includes products to treat attention deficit hyperactivity disorder (ADHD) and Alzheimer's disease, as well as depression, bipolar illness, anxiety and psychosis.

Since generic Prozac (fluoxetine) became available in fall of 2001, most payers have succeeded in switching many of their patients on a selective serotonin reuptake inhibitor (SSRIs) to generic fluoxetine, resulting in enormous savings on SSRIs. Express Scripts reported that its plan sponsors saved an average of $23.35 per Rx, for a total of $37.4 million due to the switch.

But at the same time, new drugs in other classes continue to be introduced and promoted. Geodon, an antipsychotic approved in early 2001, is now widely available on health plan formularies. This product costs more than $200 a month at retail. Abilify, an atypical antipsychotic launched by Bristol-Myers Squibb in November 2002, has not yet had an impact on health plan costs, but at retail this product is going for $365 per month. Abilify is associated with less weight gain than are traditional schizophrenia therapies.

On the antidepressant front, Pfizer's Pregabalin is a novel product in Phase III showing promise for a variety of symptoms. In trials, Pregabalin has shown efficacy at reducing symptoms as soon as one week after beginning therapy. The chief complaint about current medications is that they take a few weeks to begin working.

As many as one out of eight children may be taking ADHD medication. A study by Express Scripts, released in February 2003, found that the most commonly prescribed drugs for children were methylphenidate (Concerta, Ritalin), amphetamines (Adderall), dextroamphetamine sulfate (Dexedrine) and pemoline (Cylert).

However, drug usage for ADHD varied widely among states, indicating there are some strategies that can be employed to lower utilization. Factors cited by Express Scripts include controlled-substance laws, which vary by state; anti-Ritalin educational campaigns; direct-to-consumer advertising; physician practice style and expectations of parents and teachers.

Although Ritalin is widely available in generic versions, consumers prefer the new long-acting products that allow children to avoid a school-day dose.

Generic Savings Still to Come in Ulcer/GERD Category

The second largest category of spending is primarily driven by prescriptions for Prilosec, one of the best-selling Rx products ever. Prilosec became available in generic versions in December, and our data reflect a dip in costs for this category that correlates with this event.

Certainly the major PBMs were geared up and ready to switch their members to the new generic on an immediate basis. Generic suppliers, however, were not quite prepared to meet this demand. An initial lack of generic competition, and supply problems, challenged PBMs' plans for savings.

Meanwhile, the "little purple pill" has been replaced on television and radio by its successor, Nexium, which has demonstrated clinical advantages for severe cases of ulcer and gastroesophageal reflux disease. Still, payers are aggressively trying to control utilization of Nexium with prior authorization requirements. Most MCOs require a trial of their "preferred" formulary alternatives in this category, such as Aciphex and Prevacid. If efforts to control utilization of Nexium succeed, increased generic substitution of Prilosec could continue to pay off for plans. Peak savings will not be attained until several more generic makers enter the market.

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