The Next Blockbuster Drugs: A $170 Billion Opportunity

Safety and efficacy data are critical to drug candidates. But what really makes a potential drug attractive is strong top-line data, a new biotech-based treatment, and a massive potential market.

With help from Thomson Pharma and our own backlog of coverage, BioHealthInvestor.com, a a673b.bigscoots-temp.com website, sought to find the most promising biopharmaceutical candidate from both biotech and pharmaceutical companies in each of the top 10 most prevalent medical conditions in the U.S.

To do so, we reviewed data and Thomson Pharma revenue projections for 745 prescription drugs. We started by identifying the top sellers in each of the top 10 conditions, then looked at promising candidates that threaten to one day supplant the market leaders.  All of these challenger treatments can lead easily to a blockbuster drug status, meaning annual sales of $1 billion or more.

Click here for the top 10 medical conditions, sales estimates for the top drugs, and the up-and-coming biotech-based candidates:

1. CHOLESTEROL FIGHTERS:

Exercise. Lose weight. Avoid trans fats. Sound familiar?  Millions in the U.S. already have tried those things to some degree their bad cholesterol still is not at reasonable levels. It’s why cholesterol-lowering agents are the No. 1 type of prescribed medication in the U.S., and are expected to generate $27.4 billion in sales this year, according to Thomson Pharma estimates.

Cholesterol-lowering agents are arguably the top U.S. lifestyle drug. An American Journal of Medicine article in June suggested that Americans have worse health habits than they did 18 years ago. Waistlines are expanding. Physical activity has decreased, and so has healthy eating. It’s why doctors are apt to prescribe cholesterol-lowering drugs such as statins to patients as young as their late-20s. The drugs have been shown to cut cholesterol, and thereby reducing the risk of heart disease.

In the future, even patients with normal cholesterol levels may be prescribed statins. An American Heart Association study in November showed that AstraZeneca’s (NYSE: AZN) statin Crestor dramatically cut deaths, heart attacks and strokes in patients that had fine cholesterol levels, but high levels of a heart disease-related protein.

There are about 34 million people in the U.S. that would benefit from taking statins to cut their heart attack and stroke risk, the AHA says. But that number could potentially increase by another 10 million if the new data were to be adopted into the association’s guideline.

The class-leading drug is Lipitor from Pfizer Inc. (NYSE: PFE), with about 41 percent of the market, and expected sales of about $11.2 billion this year. Other heavyweights include Crestor, with projected sales of $4.9 billion, and Merck’s cholesterol eating non-statin, Zetia, with projected sales of $2.1 billion.

The Potential Blockbusters:

The up-and-coming cholesterol-lowering candidate to watch is a potential biopharmaceutical from Aegerion Pharmaceuticals called Lomitapide. It is a small molecule drug that works to reduce blood levels of cholesterol and triglycerides by limiting the production of lipoproteins from the intestine and liver.

Privately held Aegerion Pharma released interim Phase III data for Lomitapide in June. Among patients studied, Lomitapide reduced bad cholesterol by 44 percent. Interestingly enough, Aegerion entered into collaboration with Pfizer Inc. (NYSE: PFE) and the University of Pennsylvania for a cross-license relationship covering a range of patents related to the use of microsomal triglyceride transfer protein inhibitors.
2. INSULIN AND DIABETES TREATMENTS:

The U.S. Centers for Disease Control says that $116 billion was spent on treating diabetes in the U.S. in 2007. And because it’s a disease where a quarter of the 23.6 million affected are unaware that they have it, sales of these treatments may soon climb under proposed health care reform plans.

For many who have it, diabetes requires insulin or other daily medications. Expected 2009 spending on those drugs is $23.3 billion, according to Thomson Pharma data, second only to cholesterol-fighting drugs.

The vast majority of Americans diagnosed with the disease have Type 2 diabetes, a condition where insulin levels rise because the body fails to properly use it. Over time, the disease can cause malfunctions of the eyes, kidneys, nerves and heart. It’s a main reason diabetes is the seventh-leading cause of death.

Daily medications are a fact of life for the majority of patients with Type 1 diabetes, which used to be called juvenile diabetes. And it is creating billions in profit for drug companies that treat patients with Type 2 diabetes, as well.

Leading diabetes drugs include several long-acting insulins. Once-weekly dosing is a huge opportunity, considering the daily needle-pricks required for many with both Type 1 and Type 2 diabetes. The best-seller is the Sanofi-Aventis (NYSE: SNY) drug Lantus, with expected revenue in 2009 of more than $4 billion. Yet the current drug to beat for long-lasting insulin may be from Novo-Nordisk (NYSE: NVO), following recent data that showed a potential link to cancer risk among Lantus patients.

The Potential Blockbusters:

The true up-and-comer, however, may be an inhalable biopharmaceutical insulin candidate from Mannkind Corp. (Nasdaq: MNKD) called Afresa. It’s true that inhalable insulin has been under development for a long time that has had issues from the start. But MannKind shares recently posted a new 52-week high on Afresa study data. In a late-stage study, the Valencia, Calif.-based company said Afresa’s performance was shown to be comparable to injectable insulin.

Expectations are rising that Mankind may soon secure a worldwide marketing and development partner for Alfresa, and that it likely will be an approved product by next spring.

One possible partner might be Pfizer Inc (NYSE: PFE), which started switching its Exubera inhaled-insulin patients to MannKind’s experimental product. The companies had been partners until Pfizer pulled Exubera from the market in 2007 after showing poor sales.

3. BLOOD PRESSURE

High blood pressure has become the norm for U.S. seniors; two-thirds of Americans age 60 or older have the condition. It’s one of the most prevalent health plagues in the country, affecting men and women equally.

Overall, 29 percent of adults age 18 or older have hypertension, including about 7 percent of those who do not know they have the condition, according to the CDC. And 68 percent of those with the condition are taking medications to bring their BPs down. It’s why spending on blood pressure meds is expected to top $21.4 billion this year, according to Thomson Pharma data.

High blood pressure boosts the risk of heart attack, heart failure, stroke, and kidney disease. On the other hand, a common factor for those over 80, worldwide is normal or low blood pressure.

The CDC’s facts and figures do not include an additional 28 percent of the U.S. adult population that has pre-hypertension, a diagnoses that raises the chances of a person developing high blood pressure.

The top-selling blood pressure drug is Novartis AG’s (NYSE: NVS) Diovan. It is expected to post 2009 sales of about $5.9 billion, according to Thomson Reuters data. But that number could fall dramatically when the pill’s patent expires in 2012. The other big high-blood pressure treatment is Merck & Co. (NYSE: MRK)’s drug Cozaar, with expected sales this year of about $4.4 billion. Its patent is set to expire in 2010.
The Potential Blockbusters:

Although some concerns have been raised about its side effects, especially at high doses, the up-and-coming candidate to watch for high blood pressure is a biopharmaceutical from Gilead Sciences Inc. (Nasdaq: GILD) called Darusentan.

In May, the company announced data from one of its two Phase III clinical trials of the candidate in patients with resistant hypertension. The drug showed significant improvements in both systolic and diastolic blood pressures vs. placebo. Provided the second Phase III study backs up the efficacy data and raises no new safety concerns, the drug could receive FDA approval as early as 2011.

4. IMMUNE SYSTEM BOOSTERS/SUPRESSANTS

One giant category of drugs that covers everything from vaccines to anti-rejection transplant drugs is called immunomodulators — drugs that either stimulate or suppress the body’s immune system.

A growing number of the immunomodulators in development are biopharmaceutical compounds, such as recombinant proteins and peptides, monoclonal antibodies, and vaccines that are being used to fight multiple types of conditions and diseases, including some types of cancer.

The biggest drugs in the category are designed at least partially as a treatment for arthritis, the leading cause of disability in the U.S, and one that affects more than half of seniors. The CDC projects that the number of people age 65 or older who have arthritis or chronic joint symptoms will nearly double from 21.4 million in 2001 to 41.4 million in 2030, as more people are living longer.

About $20.7 billion is expected to be spent on immune system modulators in 2009, a number that is expected to grow as the number of treatments that work with the body’s immune system increases.

One of the top immune system suppressants — and the top-selling immunomodulator overall — is the Abbott Laboratories Inc. (NYSE: ABT) drug Humira, which works to shut down the body’s inflammatory response for patients with arthritis and Crohn’s disease. It was created using a particular type of human immune cell, which was a clone of a single parent cell. Popular competing drugs are Johnson & Johnson’s (NYSE: JNJ) Remicade, with expected sales of about $4.3 billion this year, and Amgen Inc. (NYSE: AMGN) and Wyeth’s (NYSE: WYE) Enbrel, with expected sales of about $3.4 billion.

The Potential Blockbusters:

The company to watch in immunomodulation is Array Biopharma Inc. (Nasdaq: ARRY), which has five total MEK inhibitor candidates, and two that could eventually find markets in both cancer and rheumatoid arthritis — ARRY-162 and ARRY-300.

The furthest along of the two early candidates is ARRY-162, which is now in a Phase II trial in 200 patients with rheumatoid arthritis. So far, the candidate has been well tolerated and with no patients that discontinued the study due to an adverse event. The efficacy data in that trial is expected to be released in September, an event that’s a likely catalyst for the company’s stock.

Meanwhile, ARRY has a Phase I of ARRY-300 in rheumatoid arthritis under way, and in mid-July filed an investigational new drug application for ARRY-162, in anticipation of a Phase I cancer trial.

5. ASTHMA

One type of trauma that will get you in to see an emergency room doctor than most any other is an asthma attack. The reason is simple: breathing is the most critical necessity of life.

The CDC says that about 7.3 percent of adults and 9.1 percent of children have asthma, the most common respiratory disease other than sinusitis. In 2004, the most recent CDC data available, some 4.2 percent of people in the U.S. had at least one asthma attack. The disease leads to nearly 2 million emergency room visits a year, and tens of thousands of missed days of school and work.  It’s the reason that about $20.2 billion will be spent on asthma medications in the U.S. this year, according to Thomson Pharma.

The most commonly prescribed asthma drug is GlaxoSmithKline’s (NYSE: GSK) Advair, with projected sales of $7.4 billion. It works to boost lung function by opening restricted airways and tamping down inflammation. Another popular drug is Merck & Co’s (NYSE: MRK) Singular, which helps to block genetic signals that trigger airway constriction.

The Potential Blockbusters:

Perhaps the asthma drug to watch is fluticasone furoate, developed by GlaxoSmithKline, in partnership with Theravance Inc. (Nasdaq: THRX). The two companies are working on a potential follow-up to Advair.

Glaxo and Theravance announced results of three separate Phase IIb studies of the candidate across a range of eight doses in more than 1,800 patients. Fluticasone furoate was effective in all but the lowest dose tested. Only the highest dose showed a statistically significant boost in a side effect typical of its type of inhaled steroid. A Phase III trial could start early next year.

6. ANTIPSYCHOTICS

Mental illnesses might not be top of mind when it comes to a list of top medical conditions. Yet one in four adults in the U.S. has a diagnosable mental disorder in a given year. About 6 percent have a serious mental illness, according to the National Institute of Mental Health.

One of the top mental illnesses being treated with prescription drugs is bipolar disorder, a disease that can cause extreme mood swings, from infrequent manic highs to more common depressive lows. It is the leading mental health diagnosis that contributes to lost work productivity. The median age for the disease’s onset is 25 years, which is why many with bipolar disorder are on antipsychotic medications for most of their adult lives.

Nearly $16.7 billion will be spent in the U.S. this year on medications to treat mental illnesses including bipolar disorder, according to Thomson Pharma. The top drug in the category is the bipolar disorder drug Seroquel, made by AstraZeneca plc (NYSE: AZN), with expected sales of $5.4 billion, accounting for about a third of all antipsychotic drug sales. The No. 2 drug in the category is Eli Lilly & Co.’s (NYSE: LLY) Zyprexa, for treating bipolar disorder and schizophrenia. Expected sales this year are $4.6 billion.

There are other potential markets for drug manufacturers, and for some drugs already in the category. Mental illnesses that may require antipsychotics include major depressive disorder, anxiety disorder, panic disorder, and obsessive-compulsive disorder. Many affected by mental illness have multiple disorders and phobias.

The Potential Blockbusters:

There are a number of seemingly promising antipsychotic drug candidates, but one at the top of the list is paliperidone palmitate for treating schizophrenia. The drug is being developed by Johnson & Johnson (NYSE: JNJ), with NanoCrystal technology from Elan Corp. (NYSE: ELN).

The FDA in August 2008 asked for more data on the drug before allowing it on to the U.S. market. But it has not asked for additional trials. The drug was effective in studies, with only 10 to 15 percent of patients relapsing, vs. 40 percent in the placebo group.

The main advantage of paliperidone palmitate could be in its delivery. It’s an injection taken once monthly, which in theory could make it much easier for schizophrenics to stay on their medications.

7. HEARTBURN DRUGS

Heartburn, or acid reflux, is very common, very uncomfortable, and a condition that can lead to more serious medical conditions if left untreated. It’s why $13.1 billion will be spent this year on a particular class of prescription acid reflux medications, according to Thomson Pharma data.

Roughly 60 million adults report suffering from acid reflux at least once a month, according to the American College of Gastroenterology. And about 20 percent of those people develop a more serious condition associated with immune system weakness and a higher esophagus cancer risk.

The most common prescription treatment for acid reflux is a class of drugs called proton pump inhibitors. They work to block the production of stomach acid that causes heartburn. Unlike fast-acting medications like over-the-counter antacids, proton pump inhibitors take much longer to work, but they offer long-lasting relief.

The top prescription heartburn treatment by far is AztraZeneca plc’s (NYSE: AZN) “purple pill” Nexium, with 2009 expected revenue of about $5.6 billion, and more than 40 percent market share. The No. 2 is Takeda Pharmacetical’s Prevacid, with roughly 17 percent share, and projected revenue of about $2.2 billion.

The Potential Blockbusters:

There appear to be few significant near-term challengers on the horizon to the Nexium; the drug does not start coming off patent until 2015. But one company with a candidate that could be a contender is Orexo AB, with its OX17 proton pump inhibitor. It is being developed for the treatment of gastro esophageal reflux disease, the most serious form of acid reflux. It combines two substances in an effort to provide both long-lasting and fast-acting heartburn relief.

In a Phase II trial last year, OX17 quickly proved effective in working fast and continuing to work to reduce stomach acid.  Earlier this year, Orexo signed an exclusive development deal with a yet-to-be-named partner. The company expects to announce a licensing deal for its OX17 program this year, as well.

8. ANTI-CANCER ANTIBODIES:

Cancer kills about 1,500 people a day in the U.S., more all conditions other than heart disease. And according to the American Cancer Society, it accounts for nearly one of every four deaths.  That said, there are more than 3 times the number of cancer survivors in the U.S. today than in 1970, largely due to advances in anti-cancer antibodies that are prolonging lives. About $13 billion will be spent on the drug class this year, according to Thomson Pharma.  There are many targeted cancer treatments, so our focus is on cancer treatments which have been indicated to have a broader use.

Modern cancer treatments are antibodies that target tumor cells, and have far less of an impact on healthy cells. The scientific names of all drugs in the class end in the letters “mab”, for monoclonal antibodies. Most either bind to tumor cells and release toxins, or work at the cellular level to halt the growth of tumors.

The most popular drug in the class is owned by Roche’s (RHHBY) Genentech in Herceptin, which blocks chemical signals that can stimulate breast cancer growth. Expected sales are $4.4 billion in 2009. Breast cancer is the No. 1 cancer in women, with an expected 192,370 cases this year, according to the National Cancer Institute.

The second-best selling cancer drug is Genentech’s Avastin also now under Roche after it acquired Genentech, which is used to shut off the blood supply in cancer cells that have spread to other parts of the body. It’s approved in small-cell lung cancer, as well as colon and breast cancers. Expected sales this year are about $3.2 billion.

The Potential Blockbusters:

The monoclonal antibody candidate to watch is a candidate from Eli Lilly (NYSE: LLY) via its recently acquired ImClone Systems and its IMC-1121b, which is in an ongoing Phase III trials and might some day be a rival to Herceptin for breast cancer treatment. It’s designed to block a signaling pathway that’s key to new blood vessel formation in growing tumors. It aims to stunt tumor growth by starving off the blood supply. The candidate had favorable safety and efficacy data in an early trial. It may have potential to also treat melanoma, renal and liver cancers.

There are many potential interesting anti-cancer candidates and/or new drugs, including Genentech’s breast cancer candidate Omnitarg. But the reason IMC-1121b is of particular interest is that it targets patients that cannot receive Herceptin. It also represents a bold move for ImClone if it can move into an area of biopharma where Roche’s Genentech now dominates.

9. ANTI-CLOTTING DRUGS

Blood clots are a leading killer. The CDC says about 350,000 to 600,000 Americans have a clot or one that leads to a pulmonary embolism each year, and that at least 100,000 people die as a result.  The trouble with clots is that half the people who have them do not know it; they find out when they start having chest pains labored breathing, a rapid heart rate, and seek emergency medical attention.

Anti-clotting drugs are expected to be a $10.9 billion enterprise this year, according to Thomson Pharma estimates. One main reason is that it is often prescribed as a preventive measure to those most prone to a clot, such as people who have had recent surgery, or ones that have had an artery blockage in the past, and need to be especially careful to avoid clotting.

The top name in the anti-clot game is Bristol Myers’ (NYSE: BMY) Plavix, with expected revenue of $9.5 billion this year, making it the No. 2 prescription drug in the U.S., second only to Lipitor. Plavix has about 86 percent market share. There are few noteworthy challengers, but one Ono Pharmaceuticals in Japan, with a drug called Limaprost, marketed as Opalmon.

The Potential Blockbusters:

The contender here is Eli Lilly & Co. (NYSE: LLY) with its Effient, which was approved in July 2009. It was more effective than Plavix in preventing heart attacks.

The trouble is that it also is more likely to cause problems with dangerous and sometimes fatal bleeding. As a result, Effient carries a strong black box warning. The label recommends against its use in patients with a history of heart attack or stroke. And it’s not generally recommended for anyone over age 75.  Plavix may be the older drug, and it even may be less effective, according to the study data. But it carries no such warning.

10. MULTIPLE SCLEROSIS

Unlike most diseases in the top 10, multiple sclerosis is a killer only in its most severe forms. The chronic disease affects the brain, nerves and spinal cord can affect muscle coordination and speech, making basic activities like walking and talking extremely difficult.  In its most severe form, it can cause paralysis, blindness, tremors and extreme fatigue.

About 400,000 Americans have MS, and every week about 200 people are diagnosed, according to the National Multiple Sclerosis Society. About $9.5 billion will be spent this year on prescription medications to help patients deal with MS symptoms, according to Thomson Pharma data.

The two top names in MS drugs are neck-and-neck, each with 2009 estimated sales of about $2.5 billion about 26 percent market share. One is Avonex, an immunomodulator made by Biogen Idec Inc. (Nasdaq: BIIB). It seeks to slow progression of physical disability and reduces the number of relapses by helping to limit the body’s immune response and limit damage to nerve cells. The other is generic manufacturer Teva Pharmaceutical Inc.’s (Nasdaq: TEVA) Copaxone, also an immunomodulator.  Biogen’s TYSABRI, its other MS treatment on the market, has been hamstrung due to the number of PML incidents that prompted the company to even pull TYSABRI off the market for a period.

The Potential Blockbusters:

Biogen Idec is the multiple sclerosis leader, and the candidate to watch from them is called PEGylated interferon beta-1a. The company announced earlier this month that it is enrolling patients in a global Phase II study for it, testing the safety and efficacy of bi-weekly and once-monthly injections.

Early-stage clinical trials suggest that the new candidate has the potential to offer less frequent dosing without compromising efficacy, which would be an advance over many existing drugs, including others from Biogen.  The Phase III study will examine if, over time, treatment with PEGylated interferon beta-1a can slow disease progression and lead to a decrease in the number of T2 hyperintense brain lesions commonly seen in MS patients.

-Mike Tarsala