Antipsychotic Drug Market

TOP CONTRIBUTORS

William Raasch

Antipsychotics are central nervous system therapies used to treat diseases such as schizophrenia or bipolar disorder. Patients with schizophrenia may hear "voices" or have strange thoughts that are "out of touch" with reality that can hamper their ability to carry out normal day-to-day life.^[1] Patients with bipolar disorder are characterized by mood changes that cycle between "high" manic moments and "low" depression moments.^[2] Together, the antipsychotic and antimaniac drug markets represent approximately 5 million people and generated revenues of $17.4 billion in 2008, a decline of 4% from 2007 largely driven by increased competition from lower priced generic drugs.^[3]

The major players in the antipsychotics market include AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Pfizer, Johnson & Johnson, and GlaxoSmithKline. Eli Lilly's Zyprexa has the largest market share of the market, at 26% ($4.70 billion), while AstraZeneca's Seroquel, at 2nd place ($4.45 billion) remains the most widely prescribed antipsychotic.^[4] Bristol-Myers Squibb's Abilify, which was approved for market release in 2007, saw a 30% growth in sales from 2007 to 2008 to $2.15 billion, making it the fastest growing therapeutic in the antipsychotics market. Moreover, data that Abilify may carry less of a risk for weight gain and diabetes than the incumbent therapies is driving its push for increased market share.^[5]

The antipsychotic drug market is treatened by loss of exclusivity from patent expirations. By 2012, four of the six largest antipsychotic therapies will lose their patents and see revenues decreased by generic competition.^[6] However, this threat to market size may be offset if Abilify and other novel antipsychotic therapies are shown to carry reduced risks for weight gain and diabetes.

Players in the Antipsychotic and antimaniac drug market

Eli Lilly and Company (LLY): Zyprexa

Zyprexa earned revenues of $4.70 billion in 2008, representing 23% of Eli Lilly's total earnings in that year. Total sales for Zyprexa decreased 1% from 2007 to 2008, due to decreased demand from increased generic competition.^[7] Zyprexa was approved in 2000 to treat schizophrenia. Eli Lilly's patent for Zyprexa expires on April 23, 2011.^[8]

AstraZeneca: Seroquel

Seroquel earned revenues of $4.45 billion in 2008, a growth of 9% from 2007 with sales driven by higher demand.^[9] Seroquel was originally approved in 1997 to treat patients with schizophrenia and is available in extended release tablets under the label, Seroquel XR, which only requires once-daily doses.^[10] Regulatory submissions are underway to gain approval for Seroquel as a treatment for major depressive disorder and bipolar disorder.^[11] As of 2007, Seroquel remains the most commonly prescribed atypical anti-psychotic in the US.^[12]

In February of 2009, AstraZeneca came under fire for allegations that they failed to warn physicians that Seroquel carries risks of weight gain and diabetes for prescribed patients. 9,000 lawsuits involving 15,000 patients have been filed regarding this case.^[13] AstraZeneca's patent on Seroquel expires on September 26, 2011.^[14]

Bristol-Myers Squibb and Otsuka: Abilify

Abilify earned revenues of $2.15 billion in 2008 for a growth of 30% from 2007 to 2008, driven by both higher demand and higher selling prices.^[15] Abilify was approved in 2007 as an adjunctive treatment for major depressive disorder as well as a therapeutic for schizophrenia and bipolar disorder in adolescents.^[16] BMS's patent on Abilify expires on October 20, 2014.^[17]

Johnson & Johnson: Risperdal and Invega

J&J's antipsychotics franchise, including the Risperdal formulations and Invega, earned revenues of $3.8 billion in 2008, a decrease of 24% from 2007 to 2008.^[18] Risperdal lost its patent exclusivity in March 2007, and has since seen sales decline substantially.^[19]

Invega was approved in 2007 by the FDA to treat schizophrenia.^[20] Invega contains a metabolite of the active ingredient of Risperdal in a controlled release formulation^[21] and has been criticized as not being any different from its predecessor.^[22] J&J retains exclusivity for Invega until April 27, 2010.^[23]

GlaxoSmithKline: Lamictal

Lamictal earned revenues of $1.27 billion^[24] in 2008 for a decrease of 16% from 2007 to 2008.^[25] In June of 2003, Lamictal was approved to treat bipolar disorder in adults, making it the first pharmaceutical since lithium to be approved by the FDA for bipolar disorder.^[26]

Lamictal lost its exclusivity in July of 2008^[27], and Taro Pharmaceutical's generic version was approved by the FDA in February of 2009.^[28] The increased competition will lead to a decrease in sales of Lamictal.

Pfizer: Geodon

Geodon earned revenues of $1.01 billion in 2008 for a growth of 18% from 2007 to 2008. Geodon (marketed outside the U.S. as Zeldox) is approved for the treatment of schizophrenia as well as acute mania and mixed episodes associated with bipolar disorder. Geodon is currently in development to treat Bipolar disorder.^[29] Pfizer's patents on Geodon expire on March 2, 2012.^[30]

Major Drugs in the Pipeline

• Bifeprunox (Wyeth and Solvay): Bifeprunox is a partial dopamine agonist in development to treat schizophrenia and bipolar disorder. Bifeprunox is being developed by Solvay Pharmaceuticals and was intended to be marketed by Wyeth in the United States. However, the FDA rejected Solvay's NDA for Bifeprunox in August of 2007. Solvay is still seeking approval in the EU, where it would be marketed by Lundbeck.^[32]

• Saphris (Schering-Plough): Schering-Plough added Saphris to their pipeline with the acquisition of Organon in November of 2007.^[33] Saphris is a fast-dissolving psychopharmacologic agent in development to treat patients with schizophrenia and bipolar disorder. Schering-Plough has submitted an NDA for Saphris and is awaiting a decision from the FDA for marketing approval.^[34]

• Fanapt (Vanda Pharmaceuticals): Currently in Phase III clinical trials, Fanapt is a dopamine agonist for the treatment of schizophrenia, bipolar disorders and other psychiatric conditions.^[35] Vanda Pharmaceuticals licensed Fanapt from Novartis, and has submitted an NDA for FDA approval.^[36]

Side Effects are a Concern with Antipsychotics

In 2003, the FDA required all manufacturers of atypical antipsychotics (including Risperdal, Geodon, Zyprexa, Seroquel, and Abilify) to add a warning to their drug labels that use of such drugs increases risk of hyperglycemia and diabetes mellitus.^[37] The risk of weight gain and diabetes among patients receiving atypical antipsychotics has been well documented and has arisen as a significant controversy in the antipsychotic drug market.^[38][39]

Abilify, while newer to the market and with fewer studies done of its association with weight gain compared with more incumbent antipsychotics, may carry less of a risk for weight gain.^[40] Abilify's emergence in the antipsychotics market as well as the discovery and development of novel antipsychotics that do not carry significant risks for weight gain may offset the decrease in market size due to generics in the antipsychotics market.

Patent Expirations Threaten the Antipsychotics Market

Patent expirations of two blockbuster antipsychotic medications, Risperdal and Lamictal, have already encouraged the appearance of cheap generics on the market.^[41] The appearance of generics for a therapeutic introduces competition into the market and substantially drives down the prices of those therapeutics. Several major drugs in the antipsychotic market have patent expiration dates before 2012, including Zyprexa (April 23, 2011), Seroquel (September 26, 2011), and Invega (April 27, 2010). When these therapeutics lose patent exclusivity, generics will offer psychiatrists a wide variety of cheap medications to prescribe, substantially decreasing the size of the antipsychotics market.

References

1. ↑ National Institutes of Health: Antipsychotic medications
2. ↑ National Institutes of Health: Antimanic Medications
3. ↑ The Antipsychotics Market Insight & Analysis 2008. Visiongain.
4. ↑ AstraZeneca 2008 10-K Annual Report, p.57
5. ↑ National Alliance on Mental Illness: Abilify Profile
6. ↑ FDA Orange Book
7. ↑ Eli Lilly 2008 10-K Annual Report, p.23
8. ↑ FDA Orange Book: Zyprexa
9. ↑ AstraZeneca 2008 20-F Annual Report, p.4
10. ↑ AstraZeneca 2008 20-5 Annual Report, p.21
11. ↑ AstraZeneca 2008 20-F Annual Report, p.29
12. ↑ AstraZeneca 2007 10-K Annual Report, p.57
13. ↑ Reuters: AstraZeneca downplayed Seroquel risks, lawyers say
14. ↑ FDA Orange Book: Seroquel
15. ↑ BMS 2008 10-K Annual Report, p.4
16. ↑ BMS 2008 10-K Annual Report, p.8
17. ↑ FDA Orange Book: Abilify
18. ↑ Johnson & Johnson 2008 10-K Annual Report, p.36
19. ↑ Johnson & Johnson 2008 10-K Annual Report, p.36
20. ↑ Johnson & Johnson 2007 10-K Annual Report, p.26
21. ↑ Invega (paliperidone), Son of Risperdal (risperidone), Wins FDA Okay for Schizophrenia
22. ↑ Invega: Can You Say "Patent Extender?"
23. ↑ FDA Orange Book: Invega
24. ↑ Converted from £926 million using a 1.37 pound to dollar conversation factor (British Pound Currency Exchange Forecast)
25. ↑ GlaxoSmithKline 2008 20-F Annual Report, p.35
26. ↑ Lamotrigine Drug Information
27. ↑ FDA Orange Book: Lamictal
28. ↑ Taro's ANDA for seizure drug wins FDA approval
29. ↑ Pfizer 2008 10-K Annual Report, p.2
30. ↑ FDA Orange Book: Geodon
31. ↑ Cowen and Company. Therapeutic Categories Outlook. March 2008.
32. ↑ Drug Development Technology: Bifeprunox
33. ↑ Schering-Plough Completes Acquisition of Organon BioSciences
34. ↑ Schering-Plough Submits Response to FDA for SAPHRIS
35. ↑ Vanda: Development Pipeline
36. ↑ Vanda Pharmaceuticals submits iloperidone NDA
37. ↑ Psychiatry Online: FDA to Require Diabetes Warning On Antipsychotics
38. ↑ MayoClinic Online: Antipsychotic medications: Is weight gain inevitable?
39. ↑ Atypical antipsychotics and weight gain--a systematic review
40. ↑ National Alliance on Mental Illness: Abilify Profile
41. ↑ Taro's ANDA for seizure drug wins FDA approval