Gardasil is made to the capsid proteins of HPV

Gardasil is a non-infectious quadrivalent recombinant vaccine, which delivers the major capsid (L1) protein of human papillomavirus (HPV) types 6, 11, 16 and 18 in highly purified virus-like particles, in combination wth an aluminum-containing vaccine adjuvant.

Gardasil is specifically indicated for the prevention of conditions caused by HPV types 6, 11, 16 and 18 infections. These include cervical cancer, genital warts (condyloma acuminata), and precancerous or dysplastic lesions (including cervical adenocarcinoma in situ (AIS), cervical intraepithelial neoplasia (CIN) grades 1 and 2/3, vulvar intraepithelial neoplasia (VIN) grade 2 and grade 3, and vaginal intraepithelial neoplasia (VaIN) grade 2 and grade 3).

Gardasil is supplies as a white, cloudy liquid for intramuscular injection. The recommended dosing regimen is 3 single injections of 0.5 ml of the vaccine, at day 0, 2 months after the first dose, and 6 months after the first dose.

Gardasil is a non-infectious quadrivalent recombinant vaccine, which delivers the major capsid (L1) protein of human papillomavirus (HPV) types 6, 11, 16 and 18 in highly purified virus-like particles, [the epitope]in combination wth an aluminum-containing vaccine adjuvant.

Gardasil is specifically indicated for the prevention of conditions caused by HPV types 6, 11, 16 and 18 infections. These include cervical cancer, genital warts (condyloma acuminata), and precancerous or dysplastic lesions (including cervical adenocarcinoma in situ (AIS), cervical intraepithelial neoplasia (CIN) grades 1 and 2/3, vulvar intraepithelial neoplasia (VIN) grade 2 and grade 3, and vaginal intraepithelial neoplasia (VaIN) grade 2 and grade 3).

Gardasil is supplies as a white, cloudy liquid for intramuscular injection. The recommended dosing regimen is 3 single injections of 0.5 ml of the vaccine, at day 0, 2 months after the first dose, and 6 months after the first dose.

The capsid is the outer membrane of the virus.

Busy Day with my own research today...

I will post some data I found last night as will as the specifics on Gardasil later today.

How Gardasil works post coming soon... I think it's worth a look. Cool Science

I'm reading and interpreting the data now.

Merck obtains License to Market Gardasil in Europe

WHITEHOUSE STATION, N.J.----GARDASIL(R) (Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine), the cervical cancer vaccine from Merck & Co., Inc., has been granted a license by the European Commission. GARDASIL has been approved as the first and only vaccine in the European Union (EU) for use in children and adolescents aged 9 to 15 years and in adult females aged 16 to 26 years for the prevention of cervical cancer, high-grade cervical dysplasias/precancers (cervical intraepithelial neoplasia [a different area of the cervix], high-grade/precancerous vulvar dysplastic lesions [precancer of the external vagina] and external genital warts caused by human papillomavirus (HPV) types 6, 11, 16 and 18. This license applies to the 25 countries that are members of the EU, including the five largest which are France, Germany, Italy, Spain and the United Kingdom.

Merck (MRK)closed up 9 cents today to finish at 42.04.

EPIX depressed about phase III trial failure. Shares Plunge

EPIX Pharmaceuticals (EPIX) Announces Top-Line Results From Phase 3 Trial Of PRX-00023 In Generalized Anxiety Disorder; Drug Fails Trial

LEXINGTON, Mass.--Sept. 21, 2006--EPIX Pharmaceuticals, Inc. today announced that the top-line results from its Phase 3 trial of PRX-00023, a novel long-acting 5-HT1A agonist, show that overall PRX-00023 did not achieve a statistically significant improvement over placebo for the primary endpoint. The primary efficacy endpoint was change from baseline in Hamilton Rating Scale for Anxiety (HAM-A) compared to placebo. There was a trend in favor of patients treated with PRX-00023 in the HAM-A assessments; however, the outcome was potentially impacted by a higher than expected response in the placebo-treated patients.

The data from this trial did show a statistically significant improvement from baseline in the Montgomery Asberg Depression Rating Scale (MADRS) compared to placebo. The MADRS, which measures symptoms of depression, was a secondary endpoint in this trial. EPIX is continuing to analyze the data and will use these insights to guide its strategic planning process for the development of PRX-00023.

"We are disappointed that treatment with PRX-00023 did not induce a statistically significant change in the HAM-A in patients with anxiety; however, we are encouraged by the MADRS data and will further analyze these results to better understand the potential benefits of PRX-00023 in patients with depression," said Michael G. Kauffman, M.D., Ph.D., chief executive officer, EPIX Pharmaceuticals. "Based on these top-line results, we plan to refocus our efforts away from anxiety to evaluate the benefit in depression more closely and assess opportunities for initiating a Phase 2 clinical trial in depression sooner than originally planned."

A preliminary review has indicated that PRX-00023 was well tolerated and there was a low rate of discontinuation in this study due to adverse events. Side effects, including impact on sexual function and sleep, in patients receiving PRX-00023, were similar to placebo.



What is 5-HT? What is a 5-HT agonist? What's an agonist? How does this failed drug work and why did it fail?
Let's work through this. 5-HT is short for 5-hydroxytryptamine commonly called serotonin. It was identified by accident, when blood was allowed to clot a "tonic" substance was released that caused blood vessel constriction. Serotonin plays a role several diseases. The receptor for serotonin is 5-HT1a (for this drug) is located in the hippocampus of the brain and acts as a neurotransmitter.

An agonist binds to a particular receptor and activates it. This drug binds to the serotonin receptor and is supposed to block the cell signaling that leads to depression symptoms. It failed because the patients did not show a significant difference between the drug and placebo. It's interesting that two tests were used and it passed one.
These compounds are used as antidepressants, anxiolytics, and in the treatment of migraine.

Shares of EPIX plunged today 18% to $4.32

Word of the day, Friday: Neopterin

Neopterin is a chemical released by macrophages in response to interferon-gamma. It is a common marker of immune system activation, mostly used in monitoring HIV patients. Immune modulation by T cells releasing IFN-g, IFN-alpha (cytokines) is a good indication of immune activation.

Alcon, Inc.'s TRAVATAN(R) Z Solution Approved By FDA For Treatment Of Glaucoma And Ocular Hypertensive Patients

Alcon, Inc.'s TRAVATAN(R) Z Solution Approved By FDA For Treatment Of Glaucoma And Ocular Hypertensive Patients

Sept. 21, 2006--Alcon, Inc. (NYSE:ACL - News) announced today that the U.S. Food and Drug Administration (FDA) has approved TRAVATAN® Z (travoprost ophthalmic solution) 0.004% for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension, who are intolerant of or insufficiently responsive to other intraocular pressure lowering medications. TRAVATAN® Z is a new formulation that eliminates benzalkonium chloride (BAK) from Alcon's existing TRAVATAN® solution and replaces BAK with SOFZIA(TM), a robust ionic buffered preservative system that is gentle to the ocular surface. Alcon developed this BAK-free version of TRAVATAN® because long-term use of topical solutions containing BAK may compromise the ocular surface and exacerbate conditions such as dry eye.

"Because almost 40 percent of glaucoma patients suffer from Ocular Surface Disease, TRAVATAN® Z is an advance in therapy which we believe will now enable doctors to address an unmet need of many glaucoma patients," said Kevin Buehler, Alcon's senior vice president, United States and chief marketing officer.


BAK is an anti bacterial preservative that is in most IV bags and sterile solutions. I use it in the lab to preserve western blot antibody solutions that are diluted in milk. I also use it to sterilize my cell incubators
(NYSE:ACL-- Closed today down 1.71 at 114.29.

Medivation Shares Soar on Study Results

SAN FRANCISCO — Biotechnology company Medivation Inc. said Thursday a midstage study testing its Dimebon treatment for Alzheimer's showed the drug was significantly effective, sending shares soaring in morning trading.

The Phase II clinical trial involved 183 patients with mild to moderate Alzheimer's disease at 11 sites in Russia. The drug met all five of its efficacy endpoints, which included different measurement scales for improvement in the disease, during the six-month, randomized and double-blind study.

Results also showed the drug was well tolerated with mild side effects.

"We believe that these results are important, in part because the primary and key secondary efficacy endpoints used in this trial are accepted by the Food and Drug Administration for registration of drugs to treat mild to moderate Alzheimer's disease," said Dr. David Hung, Medivation president and chief executive, in a statement.

The company has also started an extension study on the drug, which allows patients to continue treatment for up to a total of 12 months. Those results are expected in the second quarter of 2007.

Dimebon is also being studied for possible use in treating Huntington's disease.

SO, what is Dimebon and how does it work?
Dimebon was tested in Russia as an antihistamine drug and was evaluated as a representative of a new generation of anti-Alzheimer's drugs that have two beneficial actions: (1) to alleviate symptoms, and (2) to prevent progression of the disease.

The drug demonstrated cognition and memory-enhancing properties in the active avoidance test in rats treated with the neurotoxin AF64A, which selectively destroys cholinergic neurons. Dimebon protected neurons in the cerebellum cell culture against the neurotoxic action of a test protein. In vitro, Dimebon displayed Ca2+-blocking properties and pronounced anticholinesterase activity. It also exhibited strong anti-NMDA ( an ion channel receptor) activity in the prevention of NMDA-induced seizures in mice.

It works by blocking L-type calcium channels that let in Calcium which destorys neurons.
Shares surged $1.75, or 29 percent, to $7.80 on the American Stock Exchange after setting a 52-week high of $8.10 earlier in the session.

Amgen's phase II results of denosumab encouraging

Amgen said results from an exploratory analysis of an ongoing phase II study showed that subjects treated with denosumab sub-Q, 60 mg twice yearly for up to 24 months , experienced enhanced bone mineral density, as well as in parameters of hip structural analysis, which estimates bone strength.

Denosumab is a fully human monoclonal antibody that targets RANK ligand, which is a primary mediator of the formation, function and survival of osteoclasts. RANK is receptor activator of Nuclear Factor kappa B, which we have talked about in an earlier post. Post NfKB activation, a diverse array of genes are expressed in osteoclasts.

AMGEN, Nasdaq:AMGN closed up $1.03, to $72.01 in heavy trading.

Looks like I would have lost that wager,

about the US markets being down today. I completely forgot about the federal reserve announcement today. The market was actually up due to the fact that interest rates won't be raised.

I have some clinical trial data from GlaxoSmith Kline and CytRX i'll post today. I have to do some more research, then i'll put up the results.

Asian markets lower after Thai military coup

HONG KONG -- Asian stocks and currencies were lower Wednesday, with the Thai baht stabilizing at 37.745 to the dollar after touching a nearly seven-month low of 37.9 overnight in the wake of a military coup in Bangkok that overthrew Prime Minister Thaksin Shinawatra.
The Thai military ordered all banks, stock exchanges and offices to remain closed Wednesday.
The overnight move in the baht was its biggest one-day decline in three years.
Analysts said the Thai economy, with more than $60 billion in foreign exchange reserves, was in a much better fiscal position to ride out the political crisis than it was nearly 10 years ago and it was unlikely there would be a bigger impact on the region.

The Asian currency crisis that erupted July 1997 began with the devaluation of the Thai baht, then snowballed into a crisis in emerging markets around the world.
Elsewhere around the region, Japan's Nikkei 225 Average (JP:1804610: news, chart, profile) was down 1.1% at 15,696.50. The broader Topix index was down 1.4% at 1,569.61. The dollar bought 117.265 yen, down from its level of 117.58 yen in late New York trading.

Australian shares also opened lower, with the S&P/ASX 200 declining 1% to 4,967.90. The Singapore Straits Times Index was down 0.8%, while South Korea's Kospi index was down 0.6%.
Shares listed in Shanghai and Malaysia also declined. New Zealand's leading share index fell 0.9%.
Taiwan's Weighted Index traded flat.



I'll put a wager on the US market is flat as well tomorrow. How long until BioTech breaks out in fall/winter trading? There's a fall chill in the air, let's go!

Phase III GlaxoSmith-Kline Results: Boniva users Stay on Regimen Longer and have fewer Fractures

According to six-month results of ongoing studies, women with postmenopausal osteoporosis taking once-monthly Boniva® (ibandronate sodium) were approximately 25 percent more likely to stay on therapy than women taking the once-weekly medications, alendronate or risedronate.(1) To ensure the results reflect the independent effect of once-monthly dosing with Boniva, the analyses controlled for factors that could affect persistence* with therapy, including age, other medical conditions, and out-of-pocket costs for the medications -- as recommended by leading health and pharmacoeconomic research organizations.(2,3) These findings were presented today at the 28th Annual Meeting of the American Society for Bone and Mineral Research (ASBMR). The three medications studied were bisphosphonates, the most frequently prescribed class of medications for the treatment and prevention of postmenopausal osteoporosis.(4)

The findings are important in light of other presentations and previously published reports showing that staying on daily or weekly bisphosphonate therapy (persistence) may result in fewer fractures(5,6,7) and reduced healthcare costs and use of resources.(8,9,10)

"Treatment with bisphosphonates clearly reduces risk of fractures, but only if patients keep taking their medications," said lead investigator, Stuart L. Silverman, M.D., clinical professor of medicine and rheumatology at Cedars-Sinai/UCLA. He said that osteoporosis is often asymptomatic, which can reduce a patient's motivation to stay on therapy and increase their risk of debilitating fractures. "The greater persistence seen with once-monthly compared to once-weekly bisphosphonates is encouraging, particularly because the findings were consistent across two large and robust U.S. claims databases."

About the Data

These results were based on retrospective analyses of ongoing studies using two managed care databases: HealthCore and i3 Innovus, which contain prescription and health information on approximately 17.5 and 16 million enrollees, respectively.(1) These two analyses included data for 6,127 and 10,526 women who were 45 years of age or older, and who received a prescription for either once-monthly Boniva (n=277 and 1,025) or a once-weekly bisphosphonate (n=5,850 and 9,501). Patients were considered nonpersistent if they had a refill gap of 45 days or more for once-monthly Boniva, or 30 days or more for a weekly bisphosphonate. The investigators controlled for potentially confounding factors -- including age, copay and comorbidities -- as recommended by the International Society of Pharmacoeconomics and Outcomes Research and the World Health Organization.(2,3)

Compared to women who had prescriptions for a once-weekly bisphosphonate, those who had a prescription for once-monthly Boniva were 27.2 percent (p = 0.0002) and 21.7 percent (p<0.0001) more likely to persist with therapy, based on the HealthCore and i3 Innovus database analyses, respectively. The authors concluded that the increase in persistence with once-monthly Boniva was approximately 25 percent overall.(1)



This says that women on the once a month drug are more likely to stay on the medication which prevents post-menopausal osteoporosis. Women who are on daily or weekly doses of other bisphosphate drugs don't stay with the medication which results in frequent fractures and higher health care costs.
Osteoporosis is common in post-menopausal women because of the lack of hormones produced by the ovary.
In the normal bone, there are cells called osteoclasts and osteoblasts. Normally there is a lot of bone turnover, where the osteoclasts eat the bone [absorb it] and the osteoblasts creat new bone. In osteoporosis, the osteoclasts are winning the battle and absorb the bone, making it brittle.

Boniva is a bisphosphate drug, and works by inhibiting the osteoclast resorption.

GSK:NYSE closed down $1.26 today to 54.32 in heavy trading. GSK was also downgraded today to "underperform" by Bear Stearns.

Merck Moves forward with Vioxx Successor--Arcoxia

Merck Looks Forward To Reviewing The MEDAL Program Data With Regulatory Agencies And Intends To Respond To FDA-Issued ''Approvable'' Letter

Merck & Co., Inc. announced today that preliminary analyses indicate the MEDAL (Multinational Etoricoxib and Diclofenac Arthritis Long-Term) Program showed that the rate of confirmed thrombotic cardiovascular (CV) events was similar between the selective COX-2 inhibitor ARCOXIA(TM) and diclofenac, a traditional nonsteroidal anti-inflammatory drug (NSAID). Specifically, in the pre-specified "per-protocol" analysis of the primary endpoint, the relative risk of confirmed thrombotic CV events between ARCOXIA and diclofenac was 0.95 (95 percent CI: 0.81, 1.11). In the "intent-to-treat" analysis, the relative risk of confirmed thrombotic CV events between ARCOXIA and diclofenac was 1.05 (95 percent CI: 0.93, 1.19), consistent with the primary per-protocol analysis.


Merck is seeking indications for Arcoxia for the treatment of osteoarthritis, rheumatoid arthritis, chronic low back pain, acute pain, dysmenorrhea (menstrual pain), acute gouty arthritis and ankylosing spondylitis. Arcoxia is a selective COX-2 inhibitor (cyclooxygenase 2- an enzyme that is involved in the inflammatory pathway.) This drug is a NSAID, non steroidal anti inflammatory drug, like Advil. It selectively inhibits COX-2 and not COX-1 so that the intestinal tract isnt irritated.
I'll post the heart related data a little later, pretty interesting. Looks really safe.

Merck closed today up 0.38 cents to $41.18

Breaking Cancer News: Patent in Imclone Case Is Israelis

NEW YORK - In a blow to ImClone Systems Inc., a federal judge ruled Monday that three scientists from Israel are the true inventors of a patent used for the company's blockbuster cancer drug, Erbitux, rather than seven people whose names are now on it.

U.S. District Judge Naomi Reice Buchwald made the finding in a 140-page opinion that said lawyers for the scientists had proved they were entitled to sole inventorship of the patent.

Lawyers had predicted that the case could have significant effects on the future of Erbitux, a colon-cancer treatment drug made by ImClone, the company whose founder, Sam Waksal, is serving a prison sentence for his role in the stock scandal that also ensnared Martha Stewart. [Remember Ms. Stewart did not go to prison for this, she went for lying to a grand jury]

In a 2003 lawsuit, Yeda Research and Development Co. of Israel sued ImClone, which has an exclusive license for the formula used in Erbitux to inhibit tumor cells, and its partner Aventis, claiming three of its researchers were the real inventors.

During hearings this summer, plaintiffs' lawyer Nicholas Groombridge said ImClone could lose its exclusivity with the technique covered by the license if Yeda's scientists were credited. He said a ruling such as the judge's on Monday would free Yeda to license the patent to other drug companies. He said if all the names currently on the patent were taken off, ImClone would not have a license anymore.

"I presume there would be a negotiation and a deal would be reached," he said then. "It is not the intent of Yeda to keep anybody off the market."

A lawyer for Aventis later noted that one trial witness had remarked that hundreds of millions of dollars were at stake for Yeda and Erbitux, which is distributed in the U.S. by Bristol-Myers Squibb Co.

Imclone trades on the NASDAQ and is down $1.93 to $28.60 in early afternoon trading.

Tuesday's Word: Coup

Apparently, as you all know, there is an attempted coup in Thailand. And if you have seen the US market, investors are reacting by keeping their hands in their pockets. The NYSE is down 55.55 in early afternoon trading.
I'll update periodically today if any biotech-pharma companies release any data.

Monday: Word of the Day.....Methylation

Methylation occurs naturally all the time in the mammalian genome. In terms of humans, it is the addition of a CH3 group to DNA. This then inhibits the DNA from replication. Methylation is a fundamental way of how the cell regulates DNA replication. There are specific enzymes [DNA methylases] that regulate this process.

Orion Genomics is a company working on DNA methylation modifying drugs.

Gemin X Biotechnologies Initiates Phase 2 Clinical Trial Program for GX15-070 in Myelofibrosis and Hodgkin's Lymphoma

Gemin X Biotechnologies Inc. announced today the initiation of a Phase 2 clinical trial program to evaluate GX15-070 in the treatment of several types of cancer. GX15-070 is a small molecule specifically designed to inhibit all relevant members of the Bcl-2 protein family, a validated cancer target, thus restoring the natural cell death process of apoptosis.

Phase 2 trials have been initiated in Hodgkin's Lymphoma and in myelofibrosis with myeloid metaplasia. Both trials are multi-center, open-label, single agent studies that will be conducted in North America at the M.D. Anderson Cancer Center and other locations. The Hodgkin's Lymphoma trial will enroll 10-29 patients and the myelofibrosis trial will enroll 19-55 patients. The primary endpoint of the trials is tumor response, and safety, pharmacokinetics and pharmacodynamics will also be measured.

In Phase 1 studies reported to date, GX15-070 was well-tolerated and resulted in clinical and biological activity.

Results from a third study in hematological malignancies are expected to be presented at the American Society of Hematology (ASH) annual meeting this coming December.

What does all that mean? Let's take this step by step and figure it out. Bcl-2 family members are proteins inside cells that are involved in apoptosis (programmed cell death). For example, cells sense their environment or receive stimuli, and can decide to kill themselves. It is a very regulated process that proceeds step by step until rupture of the membrane. GX15 is targeted to the protein Bcl-2, which when it gets activated, pushes the cell towards apoptosis. The cool thing is that the drug inhibits Bcl-2 (and all it's family members), AND activates proteins such as Bax and Bak, which give a survival signal to the cell.
Lymphomas are immune cell cancers. Myelofibrosis is a disorder of the bone marrow where the marrow is replaced by fibrosis (scar tissue).

Gemin X is a private company in Montreal, Canada.

Generex Biotechnology Announces U.S. Distribution of New Glucose Rapidspray(TM) Product

Generex Biotechnology Announces U.S. Distribution of New Glucose Rapidspray(TM) Product
TORONTO -- Generex Biotechnology Corporation the leader in metabolic diseases drug delivery through the inner lining of the mouth, announced today that Cardinal Health will distribute its new Glucose RapidSpray™ product in the U.S.

Glucose RapidSpray is expected to be in stores by October, 2006.

Glucose RapidSpray is an innovative alternative for people who require or want additional glucose in their diet. Glucose RapidSpray delivers a fat-free, low-calorie glucose formulation that was developed using the Company's proprietary buccal drug delivery technologies. Glucose RapidSpray delivers glucose directly into the mouth where the proprietary formulation is rapidly absorbed into the blood stream. Glucose RapidSpray is simple to carry and use, with no large tablets to chew or messy gels to swallow.

"Using our patented technology -- RapidMist™ -- we've developed a product that will deliver glucose to anyone who needs a fast and efficient means for receiving glucose," said Anna Gluskin, President & Chief Executive Officer of Generex. "We expect that Glucose RapidSpray will appeal to people battling the symptoms of low blood sugar who now use other over-the-counter glucose products but want a faster-acting product. We expect to position Glucose RapidSpray as a companion product to Generex Oral-lyn™, our proprietary oral insulin spray product, in the diabetes management field."

Transmucosal glucose treatment is already used for diabetes without the discomfort of needles and pulmonary inhalation (lung). I'd like to know what the RapidSpray formulation is....

Generex trades on the NASDAQ: GNBT, and is up today 17% to $1.67.

Phase III Study Initiated for Genmab's EGF Antibody

Genmab A/S began a pivotal study of HuMax-EGFR (zalutumumab) in otherwise incurable patients with head and neck cancer, an indication that could serve as a springboard for using the human antibody more down the road.

Starting in patients who are very sick and have no other alternative the company plans to expand the product's use into first line head and neck cancer treatment and other diseases.
Patients in the study will receive an initial dose of 8mg/kg, followed by weekly infusions of maintenace doses and disease progression followed until death.

EGF stands for epidermal growth factor and tumor cells need this to sustain growth. Drugs like this are out on the market now, eg, Erbitux from Imclone, but are indicated for colon cancers.

The Copenhagen, Denmark based company saw its shares on the Copenhagen Stock Exchange (CSE:GEN lose DKK2 to close at DKK224 or $38.21. It is traded in the US as GNMSF.PK and is up to $38.25

Schering-Plough CEO Cures Host of Ills

KENILWORTH, N.J. (AP) -- Fred Hassan calls running Schering-Plough Corp. the toughest job he's ever had: taking a drug company in critical condition, treating its ills simultaneously and restoring health.
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But within 3 1/2 years, the chief executive has managed to put Schering-Plough back in the black, nudge up its stock price and cure most of the disorders he inherited from prior management. Those included slumping sales with little prospect of lucrative new drugs, a demoralized work force and multiple government probes of corporate wrongdoing and manufacturing violations.

Hassan is so well regarded as a turnaround specialist that speculation surfaced Friday Schering-Plough might try to merge with New York-based Bristol-Myers Squibb Co., which booted its CEO Tuesday. Neither company would comment on that possibility.

Schering-Plough makes prescription respiratory, cholesterol and hepatitis drugs and consumer items such as Coppertone sun care lotions, Claritin allergy pills and Dr. Scholl's foot care products. The company has been on the rebound since Hassan, a Harvard-trained MBA from Pakistan, took over.

thanks to yahoo for the article: http://biz.yahoo.com/ap/060917/schering_plough_revival.html?.v=4