Key trends in the neurodegenerative disease market
Although there are dozens of neurodegenerative diseases, most are rare or are themselves symptoms of other diseases or illnesses such as stroke, alco
By on Dec 22, 2009Although there are dozens of neurodegenerative diseases, most are rare or are themselves symptoms of other diseases or illnesses such as stroke, alcoholism or AIDS. Three of them are discussed in this article: Alzheimers, multiple sclerosis, and Parkinsons disease. These three neurodegenerative diseases are relatively more common than many others, and while their cause is not understood, they are thought to be primary illnesses rather than complications of other illnesses. Because of the large and increasing patient population and also because the options available today are minimally effective, these diseases are the targets of almost all research in the neurodegenerative field.
Neurodegenerative diseases are different from many other therapeutic areas in that the primary treatments are still closely related or nearly identical to first-generation treatments. In the 1950s, scientists determined that Parkinsons was caused by a lack of dopamine; that same decade, levadopa was used to supplement the brains own production of dopamine. Levadopa remains the primary treatment for Parkinsons.
The top-selling therapy for Alzheimers disease is an acetylcholinesterase inhibitor, a class first used to treat this disease in 1993. Multiple sclerosis treatments are still dominated by the interferons, which became the first classes with drugs approved for long-term treatment of their respective illnesses in that same year.
All three of these drug classes do not treat the disease itself but rather treat the symptoms associated with the disease. While they may extend life or improve quality of life, they do not reverse the progression of the disease. Much of the focus in neurodegenerative research is on treating the cause of the disease, rather than its symptoms, but in order to do that, the cause must first be identified. The scientific hypotheses for the cause of these diseases provide support for different drug classes. While unproven theories drive research in an indication, a failed drug trial can disprove an etiological hypothesis, and an entire class of other experimental drugs will fall with it. After the spectacular failure of Myriad Genetics experimental Alzheimers drug Flurizan, many are wondering if this will happen to the amyloid beta antibody class of therapies for Alzheimers.
These sudden class-wide disruptions do make research in the field very risky. The reward that comes with this risk, especially in the case of Alzheimers disease, is that current treatments leave much to be desired. If a new therapy proves tolerable to patients and effective enough to be approved, it is likely to see hundreds of millions or even billions of dollars of sales. This level of success is possible because the very limited treatment options for these diseases mean that patients often have no other therapies to try when first-line options cease to be effective. If a therapy can provide positive results after the primary therapy in the indication is no longer effective, it will eventually be used by most patients suffering from the disease. If it can increase quality of life when added to the currently marketed first-line treatment, it will yield even more revenue.
Growth in the Neurodegenerative Market
The majority of revenue earned from therapies treating neurodegenerative diseases comes from multiple sclerosis, as shown in Figure A. A number of factors influence this, but the largest factor is that the majority of products used to treat multiple sclerosis are biologics; as such, generic production is more complex and expensive. Even if a generics company wanted to go to the expense of setting up a manufacturing facility, it would take years or decades to recoup their investment because the FDA would require a full set of trials prior to approval. This would likely limit the market to non-US countries, eliminating the largest single market for prescription drugs.
Figure A: Total Sales for Neurodegenerative Indications, 2004-2012 (in billions)
Alzheimers therapies despite being much less effective than Parkinsons still generate five times more revenue than Parkinsons therapies. The standard-of-care drug for Parkinsons is levadopa, which has been off-patent for decades. The only source of revenue from levadopa goes to Novartis from its combination drug Stalevo, which combines patented Comtan, levadopa and carbidopa (also a generic).
Unlike Parkinsons drugs, many Alzheimers drugs remain under patent. The standard-of-care class, the acetylcholinesterase inhibitors, has not changed since 1993 when the first Alzheimers drugs came to market. The newest generation of these drugs represent a significant increase in tolerability, however, and dosing has decreased from four times a day to once a day.
Despite modestly effective drugs and a dearth of research breakthroughs, the neurodegenerative market remains one of the top-selling pharmaceutical markets. Although generic products record millions in sales and branded products which have less than $50 million in sales are not included in this study, the profiled products represent over 90% of sales in the neurodegenerative market. Sales among all profiled drugs total $18.5 billion and are expected to increase 62% to $29.7 billion by 2012.
The majority of this growth is projected to be in multiple sclerosis, which will increase from a $12.6 billion market to upwards of $20 billion in 2012. Alzheimers drugs revenue will increase from $5 billion to $8 billion, and Parkinsons will increase only $500 million dollars from its comparatively low $1 billion in sales.
No Dominating Companies, No Magic Bullets
Perhaps because no drug classes have been so successful as to render older ones obsolete, there are no largely dominant companies in the neurodegenerative pharmaceutical market. Wyeth and Eli Lilly are projected to control the amyloid beta antibody drug class, which is anticipated to be a powerful class of Alzheimers drugs. However, they will own only two drugs each in this market. And while generic giant Teva owns the rights to three different degenerative drugs, only Copaxone is projected to make more than $300 million dollars by 2012.
There are three reasons for a lack of a dominant player in this area. First, a proven next-generation drug class has not been established in any of these three indications, so research is not as focused as it is in indications such as diabetes or oncology. Parkinsons disease and multiple sclerosis drug sales also suffer from a relatively small market size, which means that there is not enough room for several different classes of successful therapies for these diseases.
Finally, much of the research is being done by small or mid-sized companies, such as Medivation, Elan or Merz Pharma, which then team up with larger companies to handle distribution. Likewise, as compounds fail, the smaller pharmaceutical companies that were pushing these drugs through early-stage clinical trials sometimes fail as well. Consequently, fewer large companies are dedicated to vetting thousands of molecules in the hopes of finding three or four that can be commercialized simultaneously.
Larger pharmaceutical companies are reluctant to take risks in these fields, where advancement in quality of treatment is sporadic. To earn distribution rights of successful compounds, they have to make deals which potentially sacrifice hundreds of millions of dollars to the drugs originator and agree to partially fund expensive Phase III clinical trials which can still result in a drugs demise.
All of these factors make evaluating the market in terms of companies, rather than in terms of compounds or brands, quite difficult. Companies may have a single product that becomes a blockbuster compound, and no other drugs in the neurodegenerative indications. Because research does not always yield promising compounds, lifecycle management for these compounds can be difficult; follow-on compounds often never materialize. Alzheimers, the largest market, has a relatively immature pharmaceutical history, and discovery of a new class of drugs could, in one to two years time, turn a multibillion-dollar blockbuster to an afterthought. Maintaining a lucrative and consistent pipeline of treatments for a neurodegenerative indication requires that large pharmaceutical companies have both luck and serious investment and, to this point, they have had neither.
This article is adapted from a study conducted by pharmaceutical intelligence firm Cutting Edge Information. To know more about the study, download summary here: http://www.cuttingedgeinfo.com/neurodegenerative-forecast/