Top 200 Drugs for 2008 by Sales

Rank	Drug	Total Retail Dollars ($000)	% change from 2007
1	Lipitor	5,880,128	-4.6%
2	Nexium	4,794,450	10.1%
3	Plavix	3,796,221	23.1%
4	Advair Diskus	3,572,473	5.4%
5	Prevacid	3,295,465	-0.6%
6	Seroquel	2,908,971	15.5%
7	Singulair	2,898,060	1.2%
8	Effexor XR	2,657,729	7.8%
9	OxyContin	2,502,982	139.8%
10	Actos	2,447,602	9.8%
11	Lexapro	2,412,048	4.7%
12	Abilify	2,371,795	33.1%
13	Topamax	2,177,348	18.5%
14	Cymbalta	2,170,162	25.2%
15	Zyprexa	1,748,259	10.7%
16	Valtrex	1,684,192	20.7%
17	Crestor	1,676,553	22.6%
18	Vytorin	1,545,643	-20.3%
19	Lamictal	1,539,101	-10.4%
20	Celebrex	1,526,818	7.8%
21	Lantus	1,475,110	13.2%
22	Levaquin	1,461,080	2.0%
23	Adderall XR	1,446,629	12.2%
24	Lyrica	1,389,205	38.9%
25	Diovan	1,283,141	14.8%
26	Tricor	1,249,299	12.9%
27	Flomax	1,236,963	23.4%
28	Risperdal	1,221,505	-31.8%
29	Diovan HCT	1,212,308	15.3%
30	Zetia	1,183,627	-15.8%
31	Aricept	1,149,221	16.9%
32	Spiriva	1,142,746	31.6%
33	Concerta	1,103,973	7.1%
34	Aciphex	1,052,133	-4.3%
35	Imitrex Oral	972,778	2.3%
36	Lidoderm	970,208	20.1%
37	Keppra	940,941	32.8%
38	Viagra	920,051	11.5%
39	Atripla	915,561	48.3%
40	Lovenox	913,764	22.5%
41	Januvia	913,501	93.7%
42	Nasonex	904,074	1.3%
43	Ambien CR	865,719	-1.2%
44	Provigil	846,089	13.6%
45	Geodon	797,100	19.9%
46	Truvada	775,787	28.0%
47	Lunesta	771,019	8.2%
48	Enbrel	763,927	-12.7%
49	Actonel	714,977	-9.6%
50	CellCept	711,530	18.7%
51	Humalog	702,798	18.7%
52	Detrol LA	696,934	9.6%
53	Depakote ER	692,472	20.0%
54	Cozaar	690,028	5.8%
55	Pulmicort Respules	651,024	9.9%
56	Niaspan	638,816	16.9%
57	Wellbutrin XL	613,694	-38.2%
58	Chantix	605,323	-20.8%
59	Budeprion XL	595,206	10.8%
60	Byetta	594,736	9.9%
61	Yaz	585,421	129.9%
62	Prograf	584,703	13.3%
63	Namenda	582,468	18.9%
64	Arimidex	568,846	12.3%
65	Combivent	558,351	4.6%
66	Cialis	555,080	22.5%
67	Flovent HFA	553,050	6.1%
68	Protonix	552,903	-74.1%
69	Premarin Tabs	548,917	-1.5%
70	Suboxone	531,808	88.4%
71	Hyzaar	528,401	5.7%
72	ProAir HFA	527,655	25.3%
73	Reyataz	519,398	18.4%
74	Benicar HCT	515,213	24.4%
75	Synthroid	514,887	-6.0%
76	Avandia	513,715	-53.7%
77	Boniva	512,179	26.7%
78	Strattera	511,612	-4.5%
79	Polymagma Plain	507,096	NA
80	Skelaxin	501,310	-3.1%
81	Evista	499,924	-0.7%
82	Asacol	463,747	10.2%
83	Depakote	456,909	-20.4%
84	Xalatan	456,321	5.9%
85	Humira	455,911	-1.4%
86	Benicar	455,408	23.2%
87	Gleevec	450,576	17.2%
88	AndroGel	441,168	20.5%
89	Enbrel Sureclick	433,792	47.9%
90	Avelox	428,793	1.0%
91	Fentanyl	423,743	3.8%
92	Lovaza	417,542	65.2%
93	RenaGel	408,552	39.2%
94	Avapro	405,557	5.4%
95	Humira Pen	381,397	99.4%
96	Vyvanse	374,990	486.1%
97	Kaletra	373,122	0.0%
98	Xopenex	371,995	4.9%
99	Copaxone	370,479	22.1%
100	Avodart	364,706	29.6%
101	Femara	360,993	23.0%
102	Avalide	355,748	8.2%
103	Ortho Tri-Cyclen Lo	350,375	-5.7%
104	Sensipar	348,365	30.8%
105	Aldara	347,587	20.9%
106	NovoLog Mix 70/30	347,106	18.7%
107	Restasis	339,110	23.4%
108	Mirapex	335,293	34.2%
109	Yasmin 28	328,905	-37.7%
110	Solodyn	316,079	40.8%
111	Lantus SoloSTAR	315,946	829.5%
112	Norvir	311,245	13.1%
113	Focalin XR	310,010	24.5%
114	Actoplus Met	301,258	31.1%
115	Vesicare	299,147	45.5%
116	Forteo	291,621	3.3%
117	Allegra-D 12 Hour	288,202	-9.0%
118	Procrit	287,898	-18.5%
119	Nasacort AQ	285,359	-10.4%
120	Tarceva	276,875	4.9%
121	Combivir	275,844	-13.3%
122	Tamiflu	275,121	138.3%
123	Avonex	273,303	2.4%
124	NuvaRing	267,259	15.9%
125	Coreg CR	265,844	83.5%
126	Epzicom	265,252	15.0%
127	Levemir	256,142	103.5%
128	Duragesic	251,699	-17.8%
129	Risperdal Consta	250,948	29.5%
130	Zyvox	249,712	5.6%
131	Tussionex	246,583	37.5%
132	Invega	246,052	146.4%
133	Fosamax	244,850	-81.9%
134	Kadian	244,504	27.9%
135	Levitra	239,860	21.4%
136	Differin	239,747	27.4%
137	Astelin	239,404	9.1%
138	Lumigan	238,436	5.1%
139	Symbicort	237,955	683.9%
140	Janumet	237,426	379.2%
141	Xeloda	236,302	17.3%
142	Clarinex	233,417	-19.2%
143	Proventil HFA	227,833	66.4%
144	Humalog Mix 75/25 Pen	226,996	11.1%
145	BenzaClin	225,984	6.0%
146	Vigamox	220,720	6.6%
147	Fosamax Plus D	218,738	-4.9%
148	Maxalt	218,686	23.7%
149	Cosopt	218,315	-10.1%
150	Requip	213,127	-47.7%
151	Relpax	213,123	0.3%
152	Patanol	211,608	-18.2%
153	Casodex	210,830	1.6%
154	Welchol	209,309	29.4%
155	Ciprodex Otic	207,845	19.3%
156	Viread	207,458	-1.6%
157	Catapres-TTS	204,665	9.2%
158	Loestrin 24 Fe	200,272	42.0%
159	Thalomid	198,528	-10.9%
160	Alphagan P	195,794	5.2%
161	Endocet	194,559	0.3%
162	Revlimid	194,505	99.8%
163	Avandamet	192,785	-29.9%
164	Maxalt MLT	192,378	19.0%
165	Altace	191,053	-73.1%
166	Budeprion SR	188,956	-6.2%
167	Pegasys	188,011	20.5%
168	Ultram ER	185,318	19.2%
169	Fentora	185,244	25.6%
170	Asmanex	185,244	14.9%
171	Rhinocort Aqua	184,397	-18.3%
172	Temodar	183,005	5.5%
173	Micardis HCT	180,407	21.8%
174	Sotret	176,782	35.3%
175	Trizivir	176,538	-13.1%
176	Enablex	176,293	19.6%
177	Isentress	175,457	>999
178	Tobradex	175,251	1.4%
179	Trileptal	170,422	-68.0%
180	Sustiva	169,984	-15.0%
181	Amitiza	169,610	41.3%
182	Micardis	165,979	18.7%
183	Zovirax Topical	164,974	8.6%
184	Ocella	164,399	NA
185	Propecia	163,166	13.7%
186	Taclonex	161,674	23.4%
187	Actiq	161,532	-29.8%
188	Valcyte	160,605	15.3%
189	Klor-Con	159,584	0.2%
190	Atacand	159,583	-0.7%
191	Doryx	158,466	20.4%
192	Veramyst	158,347	289.8%
193	Avinza	157,224	7.9%
194	Allegra-D 24 Hour	156,445	5.7%
195	Opana Er	155,662	126.7%
196	Zomig	153,913	6.7%
197	Humulin 70/30	153,026	7.2%
198	Prempro	152,633	5.4%
199	Humulin N	152,147	1.5%
200	Xopenex HFA	151,919	25.8%
	All Others	26,307,000	-15.0%
Source: Verispan, VONA

FDA Staff Asks President to Straighten Up Agency

The clearance or approval of medical devices that was not made in accordance with federal laws, rules and regulations needs to be revisited, according to a recent letter sent to President Barack Obama by disgruntled FDA employees. This is the second letter FDA employees have written to the president. “The culture of wrongdoing and cover-up is nothing new, but is part of a longstanding pattern of behavior,” the letter says.

Update on Ipsen's botulinum toxin type A Product Regulatory Review Status in the US

Ipsen (Paris:IPN) and its partner Medicis (NYSE: MRX) announced today that the companies are in active labeling and Risk Evaluation and Mitigation Strategy ("REMS") discussions with the U.S. Food and Drug Administration (“FDA”) related to the Biologics License Application (“BLA”) for Ipsen’s botulinum toxin type A product in both therapeutic and aesthetic indications.

Pharmacyclics Initiates Phase 1 Clinical Trial of Novel Oral Btk Inhibitor for Refractory B-cell Non-Hodgkin's Lymphoma

SUNNYVALE, Calif., April 13 -- Pharmacyclics, Inc. (Nasdaq: PCYC) today announced that it has begun treating patients in a Phase 1 dose-escalation study to evaluate the safety and tolerability of PCI-32765, an orally available, selective inhibitor of Bruton's tyrosine kinase, or Btk, as a potential treatment for patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). This is the first Btk selective inhibitor to be tested in humans, and is Pharmacyclics' fourth product in clinical development.

Bruton's tyrosine kinase is the gene that is disrupted in the human disease X-linked agammaglobulenemia (XLA). Patients with XLA are devoid of mature B-lymphocytes and immunoglobulins in the bloodstream, but are otherwise healthy. XLA thus provides strong clinical rationale for development of a novel therapeutic drug targeting Btk for safe inhibition of B-cell mediated diseases. In preclinical studies, PCI-32765 has the remarkable ability to selectively inhibit human B-cell activation without effecting T cells. Strong preclinical validation of Btk as a target in lymphoma was generated using PCI-32765 in a mouse model of B-cell receptor-driven lymphoma and in spontaneous B-cell lymphoma in companion canines. These studies will be reported in presentations at the 2009 AACR annual meeting in Denver, Colorado (see below). Unlike anti-CD20 protein therapies, treatment with PCI-32765 in animal models is not myeloablative, which could result in prolonged and dangerous immunosuppression for the patient.

"This is a very selective compound for B-cells, and it could represent an important alternative to rituximab therapy for the treatment of B-cell NHL. Other obvious applications include autoimmune disorders such as rheumatoid arthritis and lupus, and Pharmacyclics also has strong preclinical efficacy with PCI-32765 in these disease models," said Dr. Mark Genovese, Professor of Medicine and Co-Chief of the Division of Immunology and Rheumatology at Stanford University Medical Center and member of Pharmacyclics' Scientific Advisory Board.

"Despite recent success with biologics in the treatment of B-cell NHL, there is still a large group of patients that do not respond to therapy or who experience recurrence," said Ranjana Advani, MD, Associate Professor, Stanford University Medical Center and principle investigator of the Phase 1 clinical trial. "A drug that could not only have an impact on this patient group, but also be delivered orally would represent a significant step forward in the treatment of this disease."

This Phase 1 study is evaluating the safety and pharmacokinetics of PCI-32765 in patients with refractory B-cell non-Hodgkin's lymphoma at Stanford University, MD Anderson Cancer Center and the University of Chicago using a 28-day dose-escalation design. The study is also utilizing a proprietary pharmacodynamic assay developed by Pharmacyclics to directly assess Btk drug occupancy. Preliminary results from the Phase I trial shows good patient tolerability under conditions of Btk-drug occupancy with potent bioactivity in targeted cell populations derived from the B-cell lymphoma patients.

Pharmacyclics Btk Presentations at AACR

Monday April 20, 2009

9:30 am - 1:00 pm; Minisymposium Novel Molecular Targets / Targeting Cell Death Pathways; Experimental and Molecular Therapeutics 12 Room 405-407, Colorado Convention Center 9:40am-9:55am

#1984 Btk is a Novel Therapeutic Target to Treat Large B-cell Lymphomas Ryan M. Young, Ashley Smith, Lee Honigberg, Yosef Refaeli. National Jewish Health, Denver, CO, Pharmacyclics, Inc., Sunnyvale, CA

Tuesday April 21, 2009

8:00 am - 12:00 pm Poster Session Kinase Inhibitors 3 Experimental and Molecular Therapeutics 24 Hall B-F, Poster Section 36

8:00 am - 12:00 pm Poster Board Number 24

#3740 A Clinical Trial of the Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Naturally Occurring Canine Lymphoma. Lee A. Honigberg, Ashley M. Smith, David J. Loury, Joseph J. Buggy, Douglas H. Thamm. Pharmacyclics, Sunnyvale, CA, Colorado State University Animal Cancer Center, Fort Collins, CO

About Pharmacyclics' Btk Inhibitor Program

PCI-32765 is currently targeted for oncology while other Pharmacyclics Btk inhibitors are being developed for application to autoimmune and inflammatory diseases. Bruton's tyrosine kinase is a critical enzyme involved in B-cell activation and function, and inhibition may be useful in the treatment of a number of immune mediated diseases. B-cells are a type of white blood cell that normally play an important role in the body's immune response. However, when B-cells are overactive, the immune system produces inflammatory cells and antibodies that begin to attack the body's own tissue, leading to autoimmune disorders. Also many lymphomas are caused by uncontrolled growth of B-cells where activation of the B-cell receptor and Btk signaling are thought to play important roles.

In addition to being studied in a Phase 1 trial for refractory B-cell non- Hodgkin lymphoma, PCI-32765 has been evaluated in preclinical studies in collagen-induced arthritis, an established animal model for RA. In these studies, PCI-32765 dramatically reduced inflammation and induced regression of established disease as reported at the Federation of Clinical Immunology Societies (FOCIS) 2008 annual meeting .

Therapeutic effect of imatinib improved with addition of chloroquine

(PHILADELPHIA) The therapeutic effects of the blockbuster leukemia drug imatinib may be enhanced when given along with a drug that inhibits a cell process called autophagy, researchers from the Kimmel Cancer Center at Jefferson reported in the Journal of Clinical Investigation.

The cell-death effect of imatinib (Gleevec) was potentiated when chloroquine, an autophagy inhibitor, was given with imatinib for the in vitro treatment of chronic myeloid leukemia (CML) cells including the CML stem cells, according to Bruno Calabretta, M.D., Ph.D., professor of Cancer Biology at Jefferson Medical College of Thomas Jefferson University.

Autophagy is a process that allows cells to adapt to environmental stresses, and enables drug-treated CML cells to escape cell death. Imatinib is a tyrosine kinase inhibitor that suppresses proliferation and induces death of the malignant cells that cause CML. However, additional effects of the drug have not been studied in detail, according to Dr. Calabretta.

In this study, Dr. Calabretta's team, along with Dr. Paolo Salomoni's team from the MRC Toxicology Unit at the University of Leicester in the United Kingdom, found that imatinib induces autophagy in CML stem cells that overexpress a protein called p210BCR/ABL. Stem cells that express this protein have been historically resistant to imatinib and also to second-generation tyrosine kinase inhibitors, including dasatinib, nilotinib and bosutinib.

The autophagy process allows stem cells to survive treatment with imatinib, and continue to survive. The researchers used chloroquine to see if it would have an effect on imatinib treatment. The dual treatment with imatinib and chloroquine eliminated most CML stem cells. Also, imatinib-induced cell death was significantly increased in mice inoculated with p210BCR/ABL-expressing cells.

"Imatinib's primary effect is inhibiting the proliferation of CML cells, but the frequency of resistance increases in advanced stages of the disease," Dr. Calabretta said. "There is a need to develop new therapeutic approaches that, in combination with tyrosine kinase inhibitors, eliminate CML stem cells that escape imatinib treatment. We show that imatinib induces autophagy, which enables these cells to survive and eventually resume proliferation. We also show that chloroquine, an autophagy inhibitor, combined with imatinib actually appears to potentiate imatinib-induced cell death."

Enhancing the effects of the drug used to treat chronic myeloid leukemia

Individuals with chronic myeloid leukemia (CML) are first treated with a drug known as imatinib mesylate. Although very effective, as the disease progresses it often becomes resistant to the drug. However, a team of researchers, at the University of Leicester, United Kingdom, and Thomas Jefferson University, Philadelphia, has identified a class of drugs that might enhance the therapeutic effects of imatinib mesylate and other drugs that target the same molecule.

The team, led by Paolo Salomoni and Bruno Calabretta, observed that for several different CML cell lines and primary cells, although imatinib mesylate killed the majority of cells, a marked proportion underwent a process known as autophagy. Consistent with studies indicating that the induction of autophagy can provide a mechanism of cellular survival, suppression of autophagy using either drugs or RNA interference enhanced imatinib mesylate–induced death of CML cell lines, primary CML cells, and CML stem cells. The authors therefore suggest that inhibitors of autophagy might be used with imatinib mesylate or other drugs that target the same molecule to enhance their therapeutic benefits.

Medtronic Completes Acquisition of CoreValve Inc

In a move to further expand a comprehensive cardiovascular portfolio, Medtronic, Inc. announced the completion of its acquisition of CoreValve Inc. CoreValve develops percutaneous, catheter-based transfemoral aortic valve replacement products. Medtronic also recently acquired Ventor Technologies, Ltd., a developer of percutaneous, catheter-based transapical aortic valve replacement products. “These acquisitions position us as a leader in one of the most exciting new markets in medical devices. We expect a significant number of people with aortic stenosis to benefit from these break-through technologies,” said Bill Hawkins, chairman and CEO of Medtronic. “We have the scale and expertise to accelerate the use of these life-saving technologies.”

Epilepsy Pipeline Conference 2009 to Showcase Cutting-Edge Therapies in Development and Advances in the Treatment of Epilepsy

MIDDLEBURG, Va.--(BUSINESS WIRE)--The Epilepsy Therapy Project today announced that more than 25 emerging companies as well as leading biotechnology and pharmaceutical investors and industry executives will gather to focus on preclinical and clinical development strategies and opportunities at the Epilepsy Pipeline Conference 2009. The one-day Epilepsy Pipeline Conference 2009 will showcase the most innovative therapeutic approaches currently in development for the treatment of epilepsy. The conference will take place Friday, April 17, 2009 at the Biltmore Hotel in Coral Gables, Florida, in conjunction with the Antiepileptic Drug Trials X (AED-X) conference.

“With more than three million patients in the US alone, epilepsy represents a huge and significantly unmet medical need. We are excited to see such a high caliber group of scientific entrepreneurs presenting the latest insights and approaches to addressing epilepsy, as well as other central nervous system disorders,” said Joyce Cramer, President of Epilepsy Therapy Project. “In addition to our commitment to funding clinical research, the Epilepsy Therapy Project plays a critical role in bringing together scientific entrepreneurs with venture capital and public equity investors and pharmaceutical industry partners. Through the Epilepsy Pipeline Conference 2009 we are creating a forum to drive innovation in the discovery and development of new treatments that we hope will ultimately eradicate seizures in the next decade.”

Pipeline conference attendees will hear the latest insights from research, clinical and industry leaders, supporting informed decisions about investment in epilepsy therapy development and broader central nervous system (CNS) therapeutic areas. Investors and industry business development executives are encouraged to attend.

"With well-characterized mechanisms, therapeutic approaches, functional models and defined clinical endpoints, epilepsy is gaining recognition as an excellent starting point for companies seeking to develop new CNS diagnostics and therapeutics," said Omar Amirana, MD, Partner at Oxford Bioscience Partners. "Forums such as this provide investors, research experts and industry leaders with an opportunity to understand the major scientific and clinical advances taking place in CNS and help optimize our collective investments in future therapies."

Presenting companies at the one-day conference include: Marinus Pharmaceuticals, Sepracor, Valeant Pharmaceuticals, Icagen, NeuroTherapeutics Pharma, Neuropace and SierraNeuro, among others. In addition, the conference will feature a dynamic panel discussion between private and public investors as well as commercial business development executives on financing new epilepsy and CNS therapies.

Will Emerging Agents Disrupt the Psoriatic Arthritis Market?

DUBLIN, Ireland--(BUSINESS WIRE)--Research and Markets (http://www.researchandmarkets.com/research/e51325/will_emerging_agen) has announced the addition of Decision Resources, Inc.'s new report "Will Emerging Agents Disrupt the Psoriatic Arthritis Market?" to their offering.

Surveyed rheumatologists are open to prescribing emerging agents for psoriatic arthritis (PsA) patients upon approval. That is good news for the PsA patients who fail to respond to TNF-a inhibitors; treatment options are limited for these patients. Availability of the TNF-a inhibitors vastly improved treatment of the disease and effected a sweeping change in the approach to managing PsA. Several emerging agents offer novel approaches to treating PsA—will they prompt another shift in management of this chronic and debilitating disease?

Get the Answers You Need to Shape Your Strategy

• PsA a chronic, debilitating disease that is both - underdiagnosed and undertreated. What are the symptoms of PsA? How is the disease diagnosed? What are the risk factors for the disease? How many people in the United States and Europe have PsA? How will this population grow over the next ten years?
• TNF-a inhibitors were the first agents to receive approval for PsA. How are TNF-a inhibitors incorporated into rheumatologists' treatment choices? How will emerging treatments compete with TNF-a inhibitors?
• Because of the high cost and increased use of TNF-a inhibitors, the PsA market has experienced strong growth over the past few years. Will the PsA market continue to grow? How will emerging agents perform in the market?

Scope

• Primary research: survey of U.S. rheumatologists.
• Overview of PsA: etiology, symptoms, and diagnosis.
• Current treatments: nonsteroidal anti-inflammatory agents, conventional diseasemodifying antirheumatic drugs, and TNF-a inhibitors.
• Epidemiology: prevalent cases of PsA in the United States, France, Germany, Italy, Spain, and the United Kingdom.
• Emerging agents: Centocor/Schering-Plough/Janssen/Mitsubishi Tanabe's golimumab; Bristol-Myers Squibb's Orencia; Centocor/Medarex's Stelara; Celgene's apremilast; and Novartis's AIN-457.
• Market overview: 2007 PsA market; outlook for current and emerging agents.

Major Pharmaceutical Company to Utilize Vemics iMedicor Medical Communications Portal

NANUET, N.Y.--(BUSINESS WIRE)--Vemics, Inc. (OTCBB: VMCI) today announced that its iMedicor HIPAA compliant medical communications portal will be utilized by a major pharmaceutical company in a specialized marketing program to commence June 1.

This company, which is traded on the New York Stock Exchange, will use iMedicor to distribute customized marketing messages on a pain management product to a targeted list of over 100,000 physician specialists nationwide. These messages will comprise product-specific educational resources and will be transmitted in real time on a 24/7 basis. Doctors receiving these messages may subsequently utilize iMedicor to order product samples, set appointments with pharma sales representatives and communicate directly with pharma medical science liaisons.

In return for use of iMedicor, Vemics will receive a start-up fee plus recurring fees for the transactions listed above.

The iMedicor program is expected to significantly reduce the need for live visits by pharmaceutical sales reps to physicians’ offices, and broaden the scope and quality of communications between pharmaceutical companies and physicians. In addition, iMedicor estimates its system will slash the cost of in-person marketing by as much as 80 percent per encounter and create a higher return on investment for the pharma.

The program’s messages will be created and managed by pharmaceutical marketing firm Franklyn Ideas, which currently serves some of the world’s largest pharmas and which has engineered marketing programs for hundreds of brands.

Vemics chief executive, Fred Zolla, said, “Today’s announcement marks a milestone in our drive to provide pharmaceutical companies with state-of-the art technology delivering targeted marketing messages proven to elicit the highest rate of response among healthcare providers.

“With the pharmaceutical marketing expertise of Franklyn Ideas, we anticipate making this program an unqualified success—and one that could encourage other pharmas to follow suit.”

For cancer cells, genetics alone is poor indicator for drug response

BOSTON, Mass. (April 12, 2009) — In certain respects, cells are less like machines and more like people. True, they have lots of components, but they also have lots of personality. For example, when specific groups of people are studied in aggregate (conservatives, liberals, atheists, evangelicals), they appear to be fairly uniform and predictable. But when looked at one person at a time, individuals often break the preconceptions.
Same with cells.
Researchers tend to identify characteristics of particular cells by looking at millions at a time. As a result, they'll find that, say, "group A" responds very well to a particular cancer treatment, whereas "group B" does not. They will then often compare group A to group B to find out why.
But often ignored is that not every cell in either group behaves in ways that the aggregate indicates. In a group of cells shown to be vulnerable to a particular cancer treatment, perhaps 10 percent resist it while 90 percent succumb. While researchers have offered various explanations for this, few have studied it.
Now a group of scientists in the lab of Harvard Medical School Professor of Systems Biology Peter Sorger have studied such "outlier" cells in the context of a new and highly touted cancer drug. They have found that vastly disparate reactions occur within genetically homogeneous cell groups. These discrepancies result from protein levels that vary from cell to cell, even among cells that are identical genetic twins. What's more, these protein levels and their subsequent traits can be passed down to daughter cells—a heritability that has nothing to do with genetics.
"Genetics are permanently heritable, while these protein levels are temporarily heritable," says Sorger. "But this temporary inheritance can make all the difference in the world when it comes to the effectiveness of certain medications."
These findings are published April 12 online in Nature.
In order to investigate this disparate behavior among cells, graduate student Sabrina Spencer and postdoctoral researcher Suzanne Gaudet, both in Sorger's lab, looked at a molecule called TRAIL, a protein that causes cells to, literally, commit suicide—a process scientists call apoptosis. While TRAIL is a natural cell product, drug makers have been investigating ways to harness its power so that it can directly target cancer cells.
While TRAIL continues to be a promising drug candidate, its success rate isn't 100 percent, and the researchers wanted to figure out why.
The researchers took both cancerous and non-cancerous cells and exposed them to varying doses of TRAIL. Although these cell lines were known to be vulnerable to the molecule, a fraction always managed to survive.
The researchers noticed that when this outlier group was isolated and once again exposed to TRAIL, the cells and their immediate progeny continued to remain highly resistant for a short time. An immediate explanation might be that this group had developed some sort of genetic defense. However, when this new "resistant" group was given several days to reproduce, the pattern soon reset to the original: 90 percent died, ten percent survived.
"We knew that there were clearly factors at work here that were not genetic," says Spencer. "Genetic resistance would remain uniform in subsequent generations. But the factors at work here were clearly more dynamic."
Using a variety of imaging techniques, the researchers soon discovered that even though these cells were genetically identical —the same cell in the same tissue doing the same thing, the actual numbers of proteins in each cell varied. Specifically, proteins involved in the cell-suicide mechanism triggered by TRAIL were affected. These protein levels altered the dynamics of the entire mechanism, sometimes making cells, for all intents and purposes, immune to TRAIL. While these protein levels were initially passed on to progeny, the heritability was transient. The scientists describe it as an extra layer of inheritance, one that is superimposed onto genetic inheritance.
As for what actually causes these protein levels to vary between identical cells, the researchers cited a simple explanation: It's completely random.
"For decades biologists have had this notion that cells produce proteins in orderly, uniform ways, like an assembly line, but they don't," says Sorger. "Rather, cells produce proteins in fits and starts, and the timing and degree varies from one cell to the next—even cells that are identical in every way. This randomness is something that we're just beginning to appreciate."
These findings also offer an alternative to the cancer stem-cell hypothesis. For that, scientists have posited that certain cancers survive standard treatments because a population of tumor-specific stem cells evades chemotherapy or radiation. This paper, however, offers an alternative explanation, namely, that purely through chance, certain cells produce quantities of proteins that fundamentally alter the cell's response to treatment.
Ultimately, Sorger and his group think that this new insight will make it possible to design anti-cancer treatments that are more effective than those available today.

Pfizer To Make A Tender Offer To Increase Stake In Pfizer Limited

MUMBAI, India - Pfizer Investments Netherlands B.V., an indirect wholly-owned subsidiary of Pfizer Inc, announced today that it will make a tender offer to acquire a 33.77% stake in Pfizer Limited from public shareholders at a price of Rs. 675.00 per share.
Successful completion of this offer, assuming full acceptance, would raise the indirect stake of Pfizer Inc in Pfizer Limited to 75% from the current level of 41.23%. The offer will represent a total value of up to Rs. 6.8 billion, or approximately USD 136 million.
A public announcement will be issued in India as required by the SEBI (Substantial Acquisition of Shares and Takeovers) Regulations, 1997 (“SEBI Regulations, 1997”). The offer for these shares, which are traded on the Bombay Stock Exchange Limited (“BSE”) and the National Stock Exchange of India Limited (“NSE”), is expected to open in June 2009 and is subject to regulatory approvals. The open offer will be managed by HSBC Securities and Capital Markets (India) Private Limited.
The offer will be made at a premium of 8.6% to the closing share price of Rs. 621.55 of Pfizer Limited on April 9, 2009, on the NSE (equivalent premium of 8.3% to the closing price of Rs. 623.00 on the BSE), which was the last trading day before the announcement of the tender offer. It will also represent a premium of 22.2% over Pfizer Limited’s average share price during the 30 days ending April 9, 2009, on the NSE (equivalent premium of 22.3% over the average share price during the 30 days ending April 9, 2009, on the BSE) and a premium of 45.2% over the requisite price determined in accordance with SEBI Regulations, 1997.

FDA approves Novartis' malaria drug Coartem

Novartis’ malaria drug Coartem, which is already available in over 80 countries, has been given the thumbs-up by regulators in the USA.

The US Food and Drug Administration has approved Coartem (artemether and lumefantrine) for the treatment of acute, uncomplicated malaria infections in adults and children weighing at least five kilogrammes due to plasmodium falciparum, the most dangerous form of the disease. The approval was expected after an FDA advisory panel declared the treatment to be safe and effective in December.

Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said that because of concerns about resistance with currently available therapy, “it will benefit patients to have another treatment option for malaria”. Novartis says that Coartem is a highly-effective three-day therapy with cure rates of over 96%, “even in areas of multi-drug resistance”.

Novartis chief executive Daniel Vasella said that with a growing number of malaria cases in the USA due to rising travel, it is important to make artemisinin-based combination treatment such as Coartem, the most effective therapy for malaria, available to American patients as well."

Fighting malaria “is very much in America's interest and ACTs such as Coartem are important weapons against this infectious disease," said Tim Ziemer, the US government’s malaria coordinator. The Swiss major, which noted that it supplies Coartem for public sector use in Africa without profit, has to date provided more than 235 million treatments, which have helped save an estimated 600,000 lives, mostly children.

Sanofi to buy Brazil’s Medley for 500 million euros

Sanofi-Aventis has announced its second acquisition in a week and is to buy Brazilian drugmaker Medley.

The French firm is going to pay 1.5 billion reals (around 500 million euros) for Medley, which is Brazil’s third-largest pharmaceutical company and number one generics group, with annual sales of about 153 million euros, The deal will be completed during the second quarter.

Family-owned Sao Paulo-based Medley sells 17 of the 20 top generics in Brazil, and Sanofi noted that it employs nearly 1,550 “collaborators”, which includes a sales force of 500. The Paris-headquartered group added that the acquisition will reinforce its number one ranking among pharmaceutical companies in Brazil, with a 12% market share and make it the leading player in the field of generics in Latin America.

Sanofi noted that the Medley purchase “carries on with its strategy to build-up on growth platforms, accelerate sales and further extend its pharmaceutical portfolio in emerging markets”.

The deal comes a week after it acquired Mexican generics firm Laboratorios Kendrick. Financial details of the Kendrick purchase were not disclosed, but sales last year reached 500 million pesos, about 26 million euros. Generics is an area that Sanofi is clearly determined to expand in, having acquired the Czech firm Zentiva at the end of February for 1.8 billion euros.

A number of observers believe that Sanofi’s spending will not stop there. Rumours are doing the rounds that a bid will be forthcoming for Solvay’s pharmaceutical business, while Sanofi’s name has been linked as a possible suitor for Biogen Idec.

the leading pharmaceutical companies in the Philippines

Number one pharma company is Unilab followed by GSK, Pfizer,AstraZeneca, Sanofi-Aventiz,Novartis,Roche,Boehringer Ingelheim, MSD and BMS . This is from IMS 1st Quarter Report.

How to get started in the pharmaceutical sales industry

generally the sales person is a liaison. It is best if you have the technical background (Chemistry, Pharmacy, maybe pre-med) so you can understand and discuss the chemistry and bio-chemistry of the drugs with physicians & other purchasers who might be technical minded. You then need liberal arts skills so that you can effectively communicate that technical information to non-technical people who might be the people making the purchasing decisions, like clinic managers. You must understand what you are selling and be able to communicate why potential customers must have it whether they are of a technical mind or not. Also, you must be able to make that determination (qualify your potential customer) and speak accordingly. This is why you need the techical skills and the liberal arts skills.

Amgen Cuts 100 Jobs at Washington Manufacturing Plant

SEATTLE --An Amgen Inc. spokeswoman confirms that the drugmaker is cutting 100 jobs at its clinical drug manufacturing site in the Seattle suburb of Bothell, Wash.

Carol Pawlak says the cutbacks are not part of any larger companywide reductions. The biotechnology company has 17,000 employees worldwide.

Pawlak said Thursday the company is merging clinical drug trial work at its Bothell facility with operations at its company headquarters in Thousand Oaks, Calif.

She says laid-off employees can reapply for other positions within the company.

Xconomy, a business and technology news site that reported the job cuts, says the cutbacks leave about 70 employees in Bothell, and nearly 900 in Washington state. Pawlak confirms those figures

Scar-Reducing Drug Shows Promise

A drug designed to reduce scarring after surgery or injury has shown promising results in early human trials, UK researchers say.

Study links the Pill to increased lupus risk

It found women taking birth control pills, especially those who have just started taking them, may be 2 1/2 times more likely to contract the autoimmune disease.

The link between the two has been debated for some time. This new study in Arthritis Care and Research adds weight to earlier studies that have shown a connection.

Researchers speculate that estrogen from oral contraceptives could be responsible for the increased risk. Estrogen can affect the body's immune response which could then trigger a genetic predisposition to the disease. They add that the newer oral contraceptives are substantially less likely to increase the risk of lupus. But other experts say the risk is quite small.

Pharmaceuticals Provide a Takeover Tonic

Merger and acquisition activity has slowed dramatically as the global financial crisis restricts the ability of companies to put together debt-financed deals.
FT.com

FDA Rebuffs Teva’s Citizen Petition on Generic Copaxone Filings

The FDA has declined to review a citizen petition submitted by Teva Neurosciences asking the agency not to accept applications for generic versions of the Copaxone multiple sclerosis treatment until certain conditions are met. The agency told Teva that it would be “premature and inappropriate” to review the Copaxone (glatiramer acetate) petition filed last September. In addition, the FDA didn’t address or take action on Teva’s requests in the petition, the company says in a statement.
Generic Line

Supreme Court Asked to Review Prescriber Data Case

IMS Health and SDI Health have asked the U.S. Supreme Court to review lower court decisions on whether states may prohibit data mining — the collection and publication of prescribing trends, which drugmakers use to identify physicians who treat particular conditions for marketing purposes. Many doctors object to the tracking of their history of dispensing prescriptions. Drug companies use that information to discuss the medical benefits of products with physicians. The same data can be used by drugmakers to track the competition.

FDA Reverses Course, Drugmakers Allowed to Make Morphine Solution

Patient and hospice groups’ concerns have prompted the FDA to reverse its decision that manufacturers of morphine sulfate 20-mg/mL oral solution must stop producing the pain drug. The FDA sent nine warning letters telling companies to halt production of unapproved versions of morphine, hydromorphone and oxycodone products. The FDA is now amending those letters to allow companies to make the 20-mg/mL oral solution to meet the needs of hospice patients with severe pain, CDER Deputy Director Douglas Throckmorton said.

Medtronic Wraps Up Buy of CoreValve

US medical device company Medtronic said it has closed the acquisition of local company CoreValve, which develops products that provide an alternative to heart valve replacement surgery.

Panel Rejects Stryker OP-1 Bone Putty for PMA Approval

An FDA advisory committee voted 6–1 last week against recommending premarket approval (PMA) of Stryker Biotech’s OP-1 putty for use in an expanded patient population. The Orthopedic and Rehabilitation Devices Advisory Committee cited lingering concerns of whether the device promoted bone growth and pointed to safety issues regarding immunogenicity and maternal and fetal antibody transfer.

Minimally Invasive Technologies Expected to Be Boom Market

With the market for minimally invasive devices expected to boom over the next several years, industry is pushing government regulators to study the technology, and analysts recommend that devicemakers develop products for this market. “Over the next decade, it’s expected that all surgeries will be minimally invasive,” Lazard Capital Markets analyst Sean Lavin said. “Virtually all device companies are working toward developing products that are less invasive. … If you’re not doing something minimally invasive, you’re probably not doing business.”

Crofelemer, First-in-Class Anti-Diarrheal Agent, Positive Clinical Results to be Discussed at 13th Annual US-Japan CMSP in Kolkata, India

OUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Napo Pharmaceuticals, Inc., (“Napo”) announces that oral presentations regarding the safety, efficacy and mechanism of action of crofelemer in clinical trials in severe acute dehydrating watery diarrhea and cholera, as well as the preclinical results for other small molecule cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel blockers, will be presented at the upcoming U.S. - Japan CMSP: 13th International Conference on Emerging Infectious Diseases (EID) in the Pacific Rim – Focused on Enteric Diseases, April 6-9 in Kolkata, India. Data will also be presented on other pre-clinical anti-secretory agents. Glenmark Pharmaceuticals Limited (“Glenmark”) is currently undertaking clinical trials on crofelemer in India and anticipates introduction in the country in 2010. Glenmark has both developmental and marketing rights for the molecule in 140 countries around the world including India.

Pradip K. Bardhan of the International Center for Diarrheal Disease Research (“ICDDR”) in Bangladesh will be summarizing the results from two clinical studies that evaluated the safety and efficacy of Napo’s novel anti-secretory anti-diarrheal agent, crofelemer (NP-303), in the treatment of adult acute infectious diarrhea (conducted in India by Glenmark) and cholera (conducted at the ICCDR in Bangladesh). The study of the effects of crofelemer in adult infectious diarrhea, predominantly from enterotoxigenic Escherichia coli (ETEC) infection, was conducted without the use of any antibiotics, while the study in adult patients suffering from cholera infection was conducted in combination with a single oral dose of azithromycin. These results collectively show that crofelemer represents a first-in-class treatment option as an antisecretory agent for the treatment of acute dehydrating watery diarrhea, with or without the use of antibiotics.

Perhaps the most important application of crofelemer is to address the devastating morbidity and mortality of ~2.5 million children under 5 who die each year primarily in developing countries, from the devastation of diarrhea and dehydration of cholera and watery diarrhea due to multiple etiologies and the global crisis in access to clean water. Cholera, for example, results in death for >50% of its victims without adequate rehydration. Current standard-of-care therapy focuses on rehydration therapy and antibiotic therapy to target the infectious agent. There are no current therapies for cholera which decrease the secretion of fluid into the small intestine. Patients are at maximum risk during the first 6-18 hours. Crofelemer demonstrated significant reduction (approximately 32%) in stool volume output in the first 6 hours, a trend which continued through the first 24 hours of observation — the period of time where patients are often in a life-threatening situation due to severe dehydration. In the severe acute watery diarrhea study, overall clinical success was achieved in about 75% of the crofelemer group, including statistically significant results on all seven measurements of diarrhea symptoms. Both these studies was conducted in adults.

A separate presentation will be given by Dr. Alan S. Verkman of the Departments of Medicine and Physiology at the University of California, San Francisco, California, discussing the mechanism of action of crofelemer as a first-in-class, small molecule dual inhibitor of CFTR chloride channel and calcium activated chloride channel (“CaCC”). Furthermore, this presentation will provide some of the preclinical results with other novel small molecule inhibitors of CFTR (“second gen CFTR”), which have been exclusively licensed by Napo from the University of California regents.

(See Abstracts below)

Lisa A. Conte, CEO of Napo Pharmaceuticals, Inc. commented: "Napo is thrilled that the important results of the trials of crofelemer for cholera and for severe adult acute infectious diarrhea are being presented in such a forum and I would like to thank Glenmark, Dr. Bardhan and the ICDDR for their contributions. We look forward to Glenmark’s anticipated introduction of crofelemer in India in 2010 and in other countries thereafter. Napo is committed to the development of crofelemer for pediatric populations and collaboration with both crofelemer and second gen CFTR to address the global impact of diarrhea diseases.”

Napo’s commercial licensee for crofelemer in the United States, Salix Pharmaceuticals, Inc., expects to file an NDA for the indication of chronic diarrhea in people living with HIV/AIDS in the first half of 2010. Crofelemer is in the final Phase 3 study for this indication and has been fast-tracked by the FDA.

J&J Cutting About 900 Jobs From Pharma Unit

NEW YORK-Diversified health care products company Johnson & Johnson said Thursday it will cut about 900 jobs, mainly from its Ortho-McNeil-Janssen Pharmaceuticals unit.

The cuts include a mix of attrition and hiring freezes. They are part of the company's strategy to trim its U.S. sales force and refocus its approach in the market, according to Kara Russell, spokeswoman for the Ortho-McNeil-Janssen Pharmaceuticals unit.

The cuts amount to about 6 percent of J&J's overall pharmaceutical sales force.

In January, the maker of baby shampoo, contraceptives and other health items forecast weaker results in 2009, blaming the global recession, unfavorable currency exchange rates and intensified pressure from both generic drugs and competitors' new products.

Pfizer's Oncology Business Unit Appoints Vice President of Medical Affairs

EW YORK--(BUSINESS WIRE)--Apr 10, 2009 -

Pfizer Inc announced today the appointment of Martine J. George, M.D., M.Sc, to Vice President of Medical Affairs for its Oncology Business Unit. Dr. George will be responsible for managing external relationships with cancer agencies, organizations and specialists around the world.

“We are delighted that Dr. George – with her impressive record as a leader in global pharmaceutical organizations – will be joining Pfizer's Oncology Business Unit and look forward to her contributions in advancing science needed to bring innovative medicines to patients,” said Mace L. Rothenberg, M.D., senior vice president, Clinical Development and Medical Affairs for the Oncology Business Unit.

Dr. George possesses 20 years of experience in leading pharmaceutical organizations with expertise in medical affairs, clinical research and regulatory affairs. Most recently, she held the position of Senior Vice President of Drug Development and Chief Medical Officer atGPC Biotech, Inc. where she was responsible for the strategy and development activities for satraplatin and all early development compounds.

Her previous experience includes serving as Senior Vice President and Head of Oncology for Johnson & Johnson and as Vice President of Clinical Affairs at Ortho Biotech, Inc. Additionally, she has led the medical affairs group at Rhone-Poulenc Rorer (Sanofi-Aventis), worldwide clinical research and regulatory affairs at Gencell, and clinical research and development at Sandoz Pharmaceuticals Corporation (Novartis). Prior to joining industry she held an academic position at Institute Gustave Roussy, Villejuif, France for several years.

Dr. George received her M.Sc in Pharmacology from Montreal University in 1973, her M.D. from Paris University in 1975, and is board certified in Medical Oncology.

the Impact of the Withdrawal of Raptiva (efalizumab) on the Psoriasis Market

EXTON, Pa., April 10 On April 8th, 2009, Genentech and Roche announced the voluntary withdrawal of Raptiva (efalizumab, marketed by Genentech/Roche and Xoma) from the US market. The withdrawal comes after recent post-marketing reports of PML associated with Raptiva treatment.

BioTrends will field its fourth annual TreatmentTrends(TM): Psoriasis survey on April 13th with a special section dedicated to the impact of the Raptiva withdrawal. The on-line survey will be completed by 150 clinical dermatologists and is structured to assess treatment prevalence and brand use for topical, oral, and biologic agents. A comprehensive attribute analysis is provided for each class to indicate areas of unmet need and market share projections for the next six months. In addition, awareness and interest in products in late stage development, such as Centocor's STELARA (ustekinumab) and Abbott's ABT-874 is assessed. The report will be published in early May.

A second report offered by BioTrends, ChartTrends(TM): Biologics in Psoriasis, is a report that is based on actual patient level audit data collected through a proprietary audit tool. In this report, 1000 patients who are currently being treated with biologic agents will be reviewed to analyze the treatment algorithm that culminates in the use of biologic agents, patient demographics/co-morbidities associated with specific biologic brand use, product switching incidence and rationale, and concomitant medications. A special section focused on switches from Raptiva will be included to understand if these patients migrate to other biologic brands or are discontinued altogether from biologic therapy. This report will be published in early June.

According to last year's TreatmentTrends(TM): Psoriasis report, market share for Raptiva had steadily declined since 2006 and only 44% of the dermatologists surveyed were using the product in their practices in April 2008. Amgen/Wyeth's Enbrel and Abbott's Humira, the most frequently prescribed biologics in psoriasis, were rated significantly higher than Raptiva on nearly all of the most important attributes. However, Raptiva held a competitive advantage over all biologic competitors on its efficacy in palmo-plantar psoriasis.

New drug shows promise in treating drug-resistant prostate cancer

A new therapy for metastatic prostate cancer has shown considerable promise in early clinical trials involving patients whose disease has become resistant to current drugs.

Chemists and biologists at UCLA and colleagues at several other institutions, including Memorial Sloan-Kettering Cancer Center, have created a new drug to treat a particularly lethal form of the disease, known as castration-resistant prostate cancer, or CRPC. Also referred to as hormone-refractory prostate cancer, CRPC is resistant to further treatment by anti-hormone drugs such as Casodex and Eulexin.

In an article published April 9 in the advanced online edition of the journal Science, the scientists describe the development and testing of two novel compounds, MDV3100 and RD162, which block the androgen receptor (AR) in CRPC cells, and report results from clinical trials in which MDV3100 was found to lower prostate-specific antigen (PSA) levels — a marker for tumor growth — in men with CRPC.

The new, small organic molecule MDV3100 was "designed as a very strong antagonist of the androgen receptor to stop the growth of any prostate cancer that requires the AR for propagation, which includes most forms of prostate cancer," said Michael Jung, UCLA professor of chemistry and biochemistry and a researcher at UCLA's Jonsson Comprehensive Cancer Center, whose research group synthesized both MDV3100 and RD162.

The biology research was carried out in the UCLA departments of medicine, urology and pharmacology by Charles Sawyers and his research group; Sawyers has since moved to Memorial Sloan-Kettering Cancer Center in New York, where he serves as chair of the human oncology and pathogenesis program. The UCLA patents for both compounds were licensed by the pharmaceutical company Medivation Inc., which chose to test MDV3100 in clinical trials.

The drug has successfully completed Phase 1 and Phase 2 clinical trials, and the Food and Drug Administration has agreed to allow Medivation to begin what Jung described as "the pivotal Phase 3 clinical trials."

The results of clinical studies with MDV3100 were described at the 2009 ASCO Genitourinary Cancer Symposium in February by the trials' principal investigator, Dr. Howard Scher of Memorial Sloan-Kettering Cancer Center. In general, the drug, at 240 mg once a day, was very effective at lowering PSA levels and also in reducing the number of circulating tumor cells, without any significant toxicity.

"I think it is quite likely that the exciting results seen in the smaller population will also be evident in the larger Phase 3 trial and that the drug could be approved for use in the next few years," said Jung, who is also a member of the California NanoSystems Institute (CNSI) at UCLA.

Of 30 men with anti-androgen–resistant prostate cancer who received low doses of MDV3100 in the multisite Phase 1/2 trial designed to evaluate safety, 22 showed a sustained decline in PSA levels, an indication that their cancer was responding favorably to the drug. This trial is still underway, and results from a total of 140 patients receiving higher doses of the drug will be reported within the next year, Sawyer said.

The Phase 3 clinical trial will evaluate the drug's effect on survival in a large group of patients with metastatic prostate cancer.

MDV3100 and RD162 are second-generation anti-androgen therapies that prevent male hormones from stimulating the growth of prostate cancer cells. These new compounds appear to work well even in prostate cells that have a heightened sensitivity to hormones; that heightened sensitivity makes prostate cancer cells resistant to existing anti-androgen therapies.

Approximately 186,000 new cases of prostate cancer are diagnosed each year in the United States. The male hormones testosterone and dihydrotestosterone, which are also known as androgens, spur the growth of prostate cells, and drugs that block the receptors for these hormones are the most common treatment for the disease in its advanced, metastatic stage. Anti-androgen drugs, such as bicalutamide (Casodex), suppress the growth of cancer cells temporarily, but in most patients, the cancer ultimately develops resistance to drugs. Approximately 29,000 men in the United States die each year from the disease.

Prostate cancer becomes resistant to anti-androgen drugs when cancer cells begin to increase production of the androgen receptor, Sawyers said. When the level of androgen receptors on the cells' surface reaches a certain level, the drugs that originally suppressed the cancer actually begin to stimulate cancer growth.

Because of this backlash effect, many scientists have questioned whether blocking the androgen receptor is a wise course of action. Sawyers and his colleagues, however, believe that blocking the receptor is critical to successful treatment. They set out to design a new generation of drugs that can block the androgen receptor without unwanted side effects, even when levels of the receptor are high.

Researchers in Jung's and Sawyers' laboratories based their designs on a drug that tightly attaches to the site on the androgen receptor that binds with testosterone. If that site is blocked, the hormone cannot bind to prostate cells and tell the receptor to stimulate growth. Using this initial drug as a chemical scaffold, the researchers synthesized nearly 200 slightly different versions of the drug. They tested each one in the laboratory on prostate cancer cells that had been engineered to produce high levels of androgen receptor.

This screening yielded MDV3100 and RD162, molecules which tightly bind to the androgen receptor and do not show the cancer-stimulating effect of bicalutamide and other current anti-androgen drugs. The molecules were good candidates for drugs, because they are readily absorbed into the blood when taken orally and they persist in the bloodstream. The researchers tested the new drugs' effectiveness in mice with tumors derived from drug-resistant prostate cancer cells.

"To our delight, we found that these compounds caused very dramatic shrinkage of tumors in the mice," Sawyers said. "While treating these animals with bicalutamide produced a modest effect on their tumors, the new drugs caused the tumors to shrink dramatically, and in some animals almost completely."

Sawyers said the new drugs bind tightly enough to the natural hormone-binding site on androgen receptors to prevent most of them from functioning, even in cells with many androgen receptors.

The promising laboratory studies led Medivation to license the drugs for commercial development.

Medivation has received permission from the FDA for a large Phase 3 clinical trial of MDV3100 on about 1,200 patients with anti-androgen-resistant disease. This study will assess MDV3100's effect on cancer survival and will take several years.

While the preliminary results are promising, Sawyers said his laboratory will continue to seek further improvements in drug therapy for prostate cancer.

"There were some men in the initial trial in which the drug didn't work at all, and we want to find out why," he said. "It may be because the drug is not potent enough to overcome resistance due to androgen receptor over-expression. Or it may be that the cancers in these men are not driven by the androgen receptor anymore. Also, there were men who initially received benefit from the drug but then relapsed, and their PSA levels came back up. We want to understand the mechanism of that relapse and to try to develop drugs that prevent that renewed resistance."

For years, no treatment was available for CRPC; recently paclitaxel — a strongly cytotoxic drug — was approved.

'Unapproved' morphine to stay on market, FDA rules

WASHINGTON (CNN) -- A form of liquid morphine used by terminally ill patients will remain on the market even though it is an "unapproved drug," according to a decision by the Food and Drug Administration.

After talking with hospital and hospice organizations, which expressed concern that taking the product off the market would result in hardship for terminally ill patients and their caregivers, the agency decided to extend the usage of morphine sulfate oral solution 20 mg/ml.

The agency wants to ensure there is shortage of the drug while patients wait for an approved product to take its place.

"While the FDA remains committed to ultimately ensuring that all prescription drugs on the market are FDA approved, we have to balance that goal with flexibility and compassion for patients who have a few alternatives for the alleviation of their pain," Dr. Douglas Throckmorton, deputy director of the FDA's Center for drug Evaluation and Research, said Thursday.

"In light of the concerns raised by these patients and their health-care providers, we have adjusted our actions with regard to these particular products."

Last month, the FDA sent warning letters to nine companies telling them to stop manufacturing 14 unapproved narcotics that are widely used to treat pain.

Seven of those companies made or distributed the oral morphine.

The morphine elixir is widely used by terminal patients in hospital and home hospice care settings and is manufactured by Lehigh Valley Technologies Inc., Mallinckrodt Inc. Pharmaceuticals Group, Boehringer Ingelheim Roxane Inc. and Cody Laboratories, Inc.

In its warning letter last month, the agency gave the companies 60 days to stop manufacturing the drug before enforcement action was taken.

Thursday's announcement did not prompt immediate reactions from the companies. A spokesman for Cody Laboratories said the firm did not have all the details of the decision. Other companies did not immediately return calls from CNN.

The FDA estimates there are several thousand drugs, mostly older products, marketed illegally without FDA approval in this country. Once an illegally marketed drug is identified, enforcement action begins because the agency does not have information on the quality of these drugs and has not had an opportunity to approve their labeling. In 1976 the agency began a program to bring companies manufacturing these drugs into compliance.

Thursday's announcement applies only to the morphine sulfate elixir 20mg/ml, and the warning letters sent to the other product manufacturers are still in effect.

Currently there are no approved morphine sulfate oral solution 20mg/ml products on the market. Until there are, the FDA says it will allow companies making and distributing the unapproved drugs to continue, until 180 days after any company receives approval to manufacture a new morphine replacement drug of the same dosage.

The FDA says it expects all companies marketing unapproved drugs to submit the necessary applications to get approval for those drugs