Prohost Biotechnology. Biotech Blog, News and Comments.

A LUCRATIVE PARTNERSHIP - ARIAD AND MERCK FIGHT CANCER

admin — Fri, 13 Jul 2007 12:23:32 +0000

ARIAD (ARIA) and Merck decided to team up to develop an experimental cancer treatment, “AP23573″ - a new class of cancer small molecules that block mTOR and interfere with growth of cancer cells by starving them. The partnership could be worth more than $1 billion to Ariad, which has been testing the medication. How the market reacted is not important. The important news is that Merck has recognized the fact that mTOR is a credible target and AP23573 is doing the job.

Late-stage clinical development will start soon with the drug targeting metastatic sarcomas. The drug is also being tested for solid tumors and blood-based cancers.

Ariad will receive an initial payment of $75 million and up to $452 million more based on whether certain development goals are met. The deal could reach hundreds of millions in payments in milestone accomplishments, approval and meeting sales’ targets. Ariad will share profit with Merck in the United States and take royalties on the drug sales overseas.

STILL #1 AND #2

GENENTECH (DNA): The firm’s stock is still losing, while the sales, revenues and earnings are continuing to grow in double digits that is doubling. What could happen next. Smart investors will definitely realize that the current price represents a value below the bottom and sooner, or later, a rebound, a big one might occur.

AMGEN (AMGN) decided to take advantage of the capricious negative influence on its stock to authorize a $5 billion in increase in its share repurchase plan. The company said late Thursday it has about $1.5 billion remaining under its previous stock authorization. If you still don’t like my stock, I like it. Who would know better about Amgen than Amgen itself?

SOME MILESTONE NEWS

This News is No Invitation To Buy The Following Stocks Right Now
MEMORY PHARMACEUTICALS (MEMY) completed enrollment in its Phase 2a trial of MEM 3454, for Alzheimer’s disease.

The Drug: MEM 3454 is a partial agonist of the nicotinic alpha-7 receptor, a highly specialized receptor found in the central nervous system (CNS). Compounds acting on this receptor could be beneficial in the treatment of Alzheimer’s disease and schizophrenia, as well as other psychiatric and neurological disorders.

Results: Expected in the fourth quarter of 2007.

Partner: Roche.

CELL GENESYS (CEGE) has completed recruitment of over 600 patients into VITAL-1, the first of two ongoing Phase 3 clinical trials of GVAX immunotherapy for prostate cancer.

AMGEN AND GENENTECH BEAT CRITICS’ CAPRICE

admin — Thu, 12 Jul 2007 12:26:28 +0000

Why, will be the main headline of the Prohost E-Letter and then N-Letter that will be posted at the end of this week and the end of next week consecutively. Why do W.S. analysts not notice the biotech achievers until after they achieve? What are analysts doing? When we see that Genentech’s (DNA) 41% rise in profits fill the media, the Internet and all the running tapes, we wonder why this stock dove from around $100 to its current mid $70s price? Why the sell-off of an excellent performing company? Caprice is the answer.

Some analysts and their followers were determined to box the #1 and #2 biotech firms, and succeeded in their plan. Good for them, but bad for those who bet on winning horses and lost, despite the fact that the horses have, indeed, won many races, including the one they were told they lost. Instead of believing the photo finish, they preferred to believe those who tried to convince them that the photos are fake, the horses cannot run and they must sell their winning tickets at lower prices.

We will elaborate on the firms that W.S analysts have missed or overlooked, and those we believe are repeating the same history. Yes, some very low priced stocks nobody is paying attention to will soon fly. We know it by looking at their market caps and their promises.

DENOSUMAB

Targeting Rank Ligand
AMGEN (AMGN)

In the news, Amgen and Daiichi Sankyo Company, Limited signed a collaboration and license agreement for the development and commercialization of denosumab in Japan. Denosumab is a monoclonal antibody that targets RANK Ligand (an essential mediator of cells that break down bone).

The target is an excellent choice. Denosumab, Amgen’s antibody is in clinical trials for the prevention and treatment of a broad range of bone loss conditions including osteoporosis, bone metastases, treatment-induced bone loss, multiple myeloma and bone erosions in rheumatoid arthritis. The drug is in the first late-stage investigational therapy that specifically inhibits RANK Ligand, an essential mediator of the cells that break down bone. To know more about RNAK Ligand go to:

www.pubmedcentral.nih.gov/articlerender.fcgi?artid=152945#B5

Amgen has granted Daiichi Sankyo exclusive rights to develop and commercialize denosumab in Japan in post-menopausal osteoporosis and oncology with the potential for additional indications. Amgen will receive exclusive worldwide rights to certain Daiichi Sankyo intellectual property to the extent applicable to denosumab. The financial terms include:

- An upfront payment to Amgen of $20 million.

- Daiichi Sankyo will assume all development costs for denosumab in Japan.

- Daiichi Sankyo will pay $150 million of expected worldwide development costs for denosumab through 2009.

- Daiichi Sankyo is eligible to receive milestone payments dependent on the approval of denosumab in the European Union or Japan, in two indications.

- Daiichi Sankyo will pay royalties on annual net sales of denosumab in Japan in amounts commensurate with a major late stage product for the Japan market.

Daiichi Sankyo believes that denosumab has the potential to be a first-in-class, leading product in Japan for multiple indications. Denosumab’s potential applicability in oncology makes it an important part of the foundation for the firm’s growing oncology business.

Daiichi Sankyo has a full range of commercial capabilities, including in the primary care and hospital settings, a track record of successful large, first-in-class product launches and the financial strength to ensure appropriate investment in the product.

The drug is a potential blockbuster, as the target is unique and at the cellular origin of bone loss. Amgen remains Amgen, no matter what the critics say against this firm. Let them continue to box the stock, so good news would take it to a much higher price than any one would expect.

DENDREON’S TALE STILL ALIVE

admin — Wed, 11 Jul 2007 12:28:16 +0000

It seems that the Dendreon’s story has not ended yet and might not end soon. The metamorphosis of a cancer vaccine, Provenge, from an ineffective vaccine to a promising vaccine, to a vaccine that an FDA committee voted in favor of approving it (30 to 4), to an FDA reluctance to fully approve it despite the vote, crossed the barriers of logic. It is a mystery that requires explanation and for the first time, the high voice and the determination of the patients, the shareholders, analysts and physicians could not be ignored. Something is wrong and no matter what it is, or who committed it we decided that we want to know. It seems that there is a possibility for an explanation to come soon, as now, the SEC itself is also looking for the same.

Officials at Dendreon announced they they received a letter this week from the Securities and Exchange Commission, asking about the biotech’s Provenge clinical trials. The letter from the New York Regional Office of the SEC was an “informal inquiry, Dendreon officials said. It asks for information “related to the company’s clinical trials for Provenge, the company’s biologics license application for Provenge filed with the FDA, the FDA’s review of Provenge and the related correspondence to and from the company, from Jan. 1, 2007 through the present.”

“The SEC’s letter notes that the request should not be construed as any indication by the SEC or its staff that a violation of the federal securities laws has occurred nor should it be considered a reflection upon any person, entity or security,” Dendreon said, adding that officials intend to “cooperate fully with the SEC.”

Will the mystery be solved in favor of those patients? We have great hopes.

LUCRATIVE ALLIANCES

GENENTECH (DNA) and TERCICA (TRCA) signed a deal to develop a combo drug for kids suffering from growth failure. The agreement is about combining Genentech’s human growth hormone, with Tercica’s IGF-1. Genentech agreed to pay up to $53 million to Tercica to develop, manufacture and commercialize the combination treatment.

Tercica’s drug Increlex has become the only IGF-1 on the market after the firm won a patent battle against Insmed, which had to take its IGF-1 drug, Iplex, off the market. Tercica is combining its drug with Genentech’s Nutropin, a growth hormone, to form a once-daily injectable treatment for children who suffer from growth failure. In some cases, children do not respond to Nutropin alone, they need to add IGF-1 to it. The new combination drug will be administered once a day.

As part of the deal, Genentech is buying 708,591 shares of Tercica stock for $4 million. This is not the first time Genentech has bought shares in the smaller company. Tercica CEO Scarlett said that Genentech owns less than 5 percent of his company’s shares.

Tercica chief executive John “Chip” Scarlett said that his combo would treat a broader patient population. The combo would be for children with a projected adult growth of less than 5-foot-3 for men, and 5-foot-1 for women. Tercica won’t begin phase 2 testing until 2008.

It is a great idea that would increase the sales of both drugs.

SANGAMO (SGMO) and SIGMA-ALDRICH (SIAL) formed an alliance to develop laboratory research reagents based upon Sangamo’s ZFP technology. ZFPs are the dominant class of naturally occurring proteins known as transcription factors and are found in the nucleus of every cell. The companies said they will use ZFP nucleases to modify genes in cells and to develop and market products. Among the expected applications are “cell lines with enhanced protein production performance, panels of knock-out cell lines for

drug discovery, as well as novel stem cell and transgenic animal models.

SIGMA-ALDRICH will pay $13.75 million to Sangamo as a license fee and payment for 1 million shares of Sangamo’s stock, which it will buy at about $7.75 a share. Sangamo stands to get up to $22 million in further payments depending on the success of the program.

To know more about Sangamo and its technologies go to prohost E-letters and N-letters

HELPING CYSTIC FIBROSIS PATIENTS - GILEAD SCIENCES (GILD)

admin — Tue, 10 Jul 2007 12:30:24 +0000

Gilead Sciences (GILD): Beginning August 1, 2007, Gilead Sciences will initiate an expanded access program1 to provide its investigational therapy, aztreonam lysine for inhalation, to patients with cystic fibrosis (CF) and Pseudomonas aeruginosa (P. aeruginosa) infection who have limited treatment options and are at risk for disease progression. The expanded access program for aztreonam lysine for inhalation will be open to participating treatment centers in the United States.

The decision was based on results from two pivotal Phase 3 clinical studies, AIR-CF1 and AIR-CF2. Gilead anticipates submitting a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for aztreonam lysine by the end of 2007.

Data from AIR-CF1 study demonstrated improvement in respiratory symptoms for patients with CF.

Data from AIR-CF2 study demonstrated that aztreonam lysine for inhalation significantly improved the time to need for inhaled or intravenous (IV) antibiotics following a course of inhaled tobramycin.

Both studies also demonstrated improvements from baseline in respiratory function, as measured by relative improvement of forced expiratory volume in one second (FEV1) compared to placebo.

The most common treatment-emergent adverse events in these studies were cough, productive cough, nasal congestion, wheezing and sore throat. The incidences of these events were not significantly different between the placebo and the aztreonam lysine groups.

The Cystic Fibrosis Foundation, through its affiliate pharmacy, Cystic Fibrosis Services, Inc. will assist in drug distribution to the treatment centers.

The Program: The expanded access program will make aztreonam lysine for inhalation available to patients in the United States six years or older with CF who have P. aeruginosa present in expectorated sputum or throat swab culture within two months prior to consent. Patients with severe lung function impairment who are waitlisted or eligible for lung transplantation or who have completed participation in the open-label trial AIR-CF3 (CP-AI-006) will be eligible to participate. Patients who have a level of lung function impairment consistent with lung transplantation criteria, but who are ineligible for transplantation for other reasons, can enroll in this program.

Physicians: To participate in the program, physicians will be required to evaluate patients at screening, at baseline, at Day 28 and at Day 56 visits, and then every two months thereafter. In this program, patients will receive aztreonam lysine for inhalation, administered via the PARI eFlow® Electronic Nebulizer, 75 mg three times daily, in 56-day cycles of therapy (28 days on drug followed by 28 days off) as provided by their physician until patients or physicians withdraw from participation in the study or the program is terminated by Gilead.

The Drug: Aztreonam lysine for inhalation is an antibiotic candidate currently being studied in Phase 3 clinical trials as a treatment for people with CF who have pulmonary P. aeruginosa. Aztreonam has potent activity against Gram-negative bacteria such as P. aeruginosa. Aztreonam formulated with arginine is an FDA-approved agent for intravenous administration. Aztreonam lysine for inhalation is a proprietary inhaled formulation of aztreonam and has been designated with orphan drug status in the United States and Europe.

Gilead intends to expand the program to additional patient populations in defined stages. For more information regarding the expanded access program or to request registration materials, physicians may call 1-800-490-2697 or log on to www.EAPforCF.com.

1 Expanded access programs are part of an effort by the FDA and the pharmaceutical industry to make investigational drugs available during the later stages of clinical development for the treatment of serious or life-threatening diseases.

GILD, ALNY AND NWBO:OB? - The Road Towards Success

admin — Mon, 09 Jul 2007 12:31:45 +0000

GILEAD: A SUCCESS STORY

Barron’s believes that shares of Gilead Sciences (GILD) could soar 20 percent to 25 percent on strong demand for its existing AIDS and flu drugs as well as from new products in the pipeline. Why not if the earnings are climbing by double digit every year and the journal believes it will climb another 25 percent this year to $1.50 to $1.55 per share. Barron’s quotes Chief Executive John Martin as saying, “For the past 20 years, I have been asked every year if the growth now will slow. It hasn’t and won’t. I continue to see developing value for stockholders. I continue to see a very exciting future for this company.”

GILD is a Prohost selection and resides in Prohost table since years. It is still there.

RNAi DRUG DEVELOPING IS WORTH BILLIONS

In other important news about another firm in Prohost selection comes from Alnylam (ALNY). Roche Holding has signed an agreement worth up to $1 billion with this RNAi specialized firm, giving it access to the U.S. firm’s skills in the new science of RNA interference. The agreement is the largest drug discovery partnership in the field to date. It validates the RNAi technology and drug development, in which Alnylam has become the most visible and most active.

Roche will pay Alnylam $331 million upfront in cash and equity investment, including a stake of 1.975 million Alnylam shares at $21.50 each, or just under 5 percent of Alnylam’s outstanding common stock. The pharmaceutical firm will get a non-exclusive license for Alnylam’s technology platform. The alliance will initially focus on oncology, respiratory diseases, metabolic diseases and certain liver diseases. Roche will also acquire Alnylam’s European research site at Kulmbach, Germany, which will become the Swiss group’s Center of Excellence for RNAi therapeutics discovery.

Novartis AG had bought a 19.9 percent stake in 2005 for $11.11 a share.

RNA interference, or RNAi, is a unique way of preventing diseases at their root origin, when feasible. It is a naturally occurring phenomenon where the body blocks RNA from manufacturing harmful proteins that are important parts of disease pathways. The technology seems to be more trusted than antisense and has attracted large pharmaceutical companies. Last year Merck paid $1.1 billion to buy the RNAi specialized firm Sirna. Also, RNAi was the basis for last year’s Nobel Prize in medicine. It has potential to block the chains of reactions that form pathways of many diseases, including cancer.

Last Friday AstraZeneca Plc signed a smaller RNAi deal, worth up to $400 million, with Britain’s Silence Therapeutics Plc (LSE:SLNL)

IS THIS TRUE?

A personalized Brain Cancer Vaccine To Reach The Swiss

NORTHWEST THERAPEUTICS (NWBO:OB)

Northwest Biotherapeutics (NWBO :OB) announced that it has received Authorization for Use to make its DCVax®-Brain commercially available for treatment of brain cancer patients in Switzerland. DCVax®-Brain is the first commercially available therapeutic vaccine for such cancers. The Company intends to begin making the product available to patients in Q3 2007.

Northwest Biotherapeutics has become the first company to market a personalized therapeutic vaccine for brain cancers, which has a bad prognosis for patients today.

Under the Swiss Authorization for Use, the Company is permitted to manufacture DCVax®-Brain in the US and make it available for the treatment of patients with brain cancer at select centers in Switzerland. The Authorization was granted in response to the Company’s application in mid-February, 2007. It was based upon the Company’s clinical data to date, and upon an extensive inspection by Swissmedic (the Swiss Agency for Therapeutic Products) on behalf of the BAG.

DCVax® works by mobilizing the full spectrum of immune response, both innate and adaptive, rather than just single immune agents such as antibodies alone or T cells alone. As such, DCVax® mobilizes the patient’s immune system to function in its normal, natural way. This leads to both improved efficacy and lack of problematic toxicities. Unlike conventional cancer drugs, DCVax® does not cause any debilitating side effects.

DCVax® products are personalized treatments, made by combining a patient’s own master immune cells (dendritic cells) with cancer biomarkers derived from or displayed by the patient’s own tumor. Precursors of the master immune cells are continuously circulating in a patient’s blood and are obtained through a blood draw. The master immune cells are then matured and activated through a series of proprietary steps, then “educated” by exposure to the patient’s tumor biomarkers, and injected back into the patient through a simple intradermal injection in the arm or thigh, consisting of just a few drops.

Unlike many personalized therapies under development, DCVax® products will be cost-effective. The key to their cost-effectiveness is a proprietary batch manufacturing process pioneered by NWBT, through over 10 years of development, under which a single manufacturing run is used to produce at least 3 years of personalized treatments for a particular patient. The treatments are stored frozen in single-dose vials, ready for use on an off-the-shelf basis for that patient. Such storage is highly reliable and low cost. By doing only one manufacturing run, and thereafter having the product available off-the-shelf, NWBT is able to keep the costs of its personalized vaccines at a level that can enable product pricing in a range comparable to other cancer drugs.

In parallel with making DCVax®-Brain commercially available to patients at selected medical centers in Switzerland, NWBT is also conducting a Phase II pivotal trial in 141 patients in the US. The trial began enrolling patients in December 2006, and is anticipated to conclude around the end of 2008. The Company plans to seek product approval in both the US and EU in early 2009, based upon the results of the Phase II pivotal trial.

DCVax®-Brain has been granted orphan drug status in both the US and the EU. Such status will afford DCVax®-Brain 7 years of market exclusivity in the US and 10 years in the EU, if DCVax®-Brain is the first product of its type to reach product approval.

Clinical trial data to date in brain cancer patients have shown that DCVax®-Brain delays disease recurrence by nearly 3-fold, from 6.9 months to 18.1 months for newly diagnosed patients. DCVax®-Brain also extends these patients’ survival from 14.6 months to more than 33 months (and continuing — median not yet reached).

The DCVax® Technology platform is anticipated to be applicable to most cancers. NWBT is already at the Phase III, pivotal trial stage in prostate cancer, and has also received FDA clearance for clinical trials in five other cancers (including lung cancer, the leading cause of cancer deaths worldwide). Clinical trial data to date in hormone independent prostate cancer patients have shown striking results similar to the results in brain cancer.

About Prohost

admin — Sun, 01 Jul 2007 17:55:42 +0000

ABOUT PROHOST

The enormous advancement in the biological sciences that is taking place has begun to change the traditional way of practicing medicine. Far-reaching biological products are being approved and news about breakthroughs are occupying the headlines. However, selecting the biotechnology firms in which to invest requires not only an understanding of the company’s finances, but also a knowledge of the company’s potential and the potential and scientific validity of it’s products and technologies.

Our Mission

Prohost evaluates biotechnology companies, their products and technologies, their scientists and managers, as well as their finances. Our goal is to impart our readers with the knowledge
and insight so that they may have a heightened understanding and appreciation for the biotechnology industry. We hope this newfound insight can help our readers identify the newest blockbuster technologies and discover the next industry leaders.

Company Profile

Prohost is the premier biotechnology newsletter. In printed form, The Prohost Biotechnology Newsletter has been in circulation since 1992. Our readers are comprised of fund managers, investors, medical professionals and all kinds of individuals with one common interest, biotechnology.

Prohost publishes a monthly Newsletter and a weekly Faxletter. Both the Newsletter and the Faxletter are posted on the web in the Members’ Area. Besides being available on the web, the Newsletter (12 pages) is mailed to all the subscribers. The Faxletter is also dispatched by fax or e-mail. Subscription to the Faxletter includes the Newsletter.

Prohost is ranked #1 from among 355 publications by an independent accounting firm hired by Select Information Exchange (SIE). Newsletters were rated based on their performances over the two year period of 1999 and 2000.

NEXAVAR

admin — Wed, 27 Jun 2007 16:41:45 +0000

On The Road To Becoming A Blockbuster

Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals (ONXX) submission of a Supplemental New Drug Application (sNDA) for Nexavar® (sorafenib) tablets is a historical event. It is, indeed, because the drug is intended for a terrible cancer, hepatocellular carcinoma (HCC) that is killing patients with no treatment in the hands of oncologists and with a history of 100 experimental treatments failing to demonstrate safety and efficacy. The drug is already approved for kidney cancer, which is as awful as liver cancer.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Death rates from liver cancer continue to increase. HCC is responsible for about 90 percent of the primary liver cancers in adults. It is the fifth most common cancer in the world and the third leading cause of cancer-related deaths globally. Over 600,000 cases of HCC are diagnosed globally each year (about 19,000 in the United States and 32,000 in the European Union and in 2002 approximately 600,000 people (about 13,000 Americans and 57,000 Europeans) died of HCC.

Nexavar is the first drug to demonstrate a significant survival benefit with HCC, and, if approved, it would fulfill a serious unmet need with a manageable toxicity profile.

Why the Submission? The positive data from the international, Phase 3, placebo-controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) trial. The trial results demonstrated that Nexavar extended overall survival by 44 percent in patients with HCC (HR=0.69; p=0.0006) versus placebo. Side effects are manageable.

Vision: Onyx believes that Nexavar will become the reference standard of care in HCC, and will help advance the firm’s development program. Onyx’ plan includes clinical trials studying Nexavar alone and in combination with other therapies for melanoma, non-small cell lung and breast cancer.

What is Nexavar?

Nexavar is a small molecule drug with dual action. The drug targets both the tumor cell and tumor vasculature. Its targets members are two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply) — both contribute to cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET. Preclinical models have demonstrated that Raf/MEK/ERK has a role in HCC; therefore blocking signaling through Raf-1 may offer therapeutic benefits in HCC.

Side effects:

Hypertension may occur early in the course of therapy and blood pressure should be monitored weekly during the first six weeks of therapy and treated as needed.

Incidence of bleeding regardless of causality was 15% for Nexavar vs. 8% for placebo.
Cardiac ischemia/infarction was 2.9% for Nexavar vs. 0.4% for placebo.

Most common adverse events were diarrhea, rash/desquamation, fatigue, hand-foot skin reaction, alopecia, and nausea. Grade 3/4 adverse events were 38% for Nexavar vs. 28% for placebo. Women of child-bearing potential should be advised to avoid becoming pregnant and advised against breast-feeding. In cases of any severe or persistent side effects, temporary treatment interruption, dose modification or permanent discontinuation should be considered.

COMMENTS ON PDLI, CURAGEN AND OTHER NEWS

admin — Wed, 20 Jun 2007 16:44:09 +0000

CURAGEN (CRGN) has made the right decision, closing its pilot manufacturing plant, effective July 27, 2007. The firm needed to reduce its expenses and focus on its promising investigational drugs in mid-clinical trials, which hold the hope for success. Curagen has promising products (See past Letters and web postings). The firm decided to reduce the workforce by approximately 40 employees.

PDL BIOPHARMA (PDLI): There is talk about meetings between this firm and Third Point LLC with regard to management changes. Could PDLI’S CEO be forced out? Anything can happen. The most important is that large equity investors’ influence, caprice or not, ends up in favor of the firms’ values. PDLI is an excellent biotech and will remain excellent.

Good news has also come from the firm Lexicon Pharmaceuticals (LXRX)

IN THE SPOTLIGHT

Anticoagulants: Many firms are developing advanced anticoagulants, which aim at lessening the possibility of hemorrhages. Stroke caused by current anticoagulants is causing big problem to physicians and patients susceptible to clot formation. Numerous diseases, cardiac, vascular, hereditary and some surgeries subject patients to clot formation, which could cause heart attacks or strokes. Giving the currently available anticoagulants protects these patients from clots, but subjects them to hemorrhage, which could have worst consequences. So, successful new blood thinners could be of great value to those patients and the physicians. Prohost will tackle this subject in the upcoming N-Letter.

AN APPROVAL FOR GILEAD AND APPROVABLE LETTER FOR ENCISIVE

admin — Mon, 18 Jun 2007 16:48:37 +0000

The FDA approved Gilead’s (GILD) drug Letairis (ambrisentan) for pulmonary hypertension.

The disease: Narrowing and thickening of pulmonary (lung) arteries cause an elevation of the patients’ blood pressure. Among the symptoms are shortness of breath and exhaustion, which makes patients unable to exercise, or walk distances. The disease could cause heart failure and could be fatal if not treated.

The drug: Letairis belongs to a class of drugs called ERAs, or endothelin receptor antagonists. It relaxes the arteries, lowering blood pressure, hence, decreasing the extra load on the heart and lungs. In experimentation, the drug improved patients’ capacity to exercise. The drug is indicated as a once-daily treatment of pulmonary arterial hypertension (WHO Group 1) in patients with WHO Functional Class II or III symptoms to improve exercise capacity and delay clinical worsening. Letairis will be available in the United States early next week. Because of the risks of liver injury and birth defects, the product will be available through the Letairis Education and Access Program (LEAP), a restricted distribution program designed to help patients learn about the risks of Letairis.

The drug’s label will carry strong cautionary language in a black box, as do other drugs of its class. Gilead says its studies show that incidence of liver damage is less with Letairis than with other products in this class. The company said Letairis will be available only through a special restricted program to educate patients and doctors about safe usage.

Price: Gilead said it has priced the drug at $3,940 a month, comparable with other oral drugs for the disease. Gilead said it established a program to ensure greater access to patients who are underinsured or face high co-payment requirements.

Incidence: Gilead said it estimates about 75,000 to 90,000 people in the US suffer from PAH, and 200,000 people worldwide, although fewer than half of them are currently believed to be diagnosed. The condition is often misdiagnosed as exercise-induced asthma or other respiratory ailments.

Marketing: Gilead in the US and GlaxoSmithKline PLC outside the U.S. Currently the drug is under regulatory review in Europe and Canada, and GlaxoSmithKline is doing studies in Japan aimed at getting approval there.

The Bad News

A drug developed by Encysive Pharmaceuticals (ENCY) for the same disease, i.e., pulmonary arterial hypertension, did not satisfy the requirements of the FDA for final approval. The agency issued its third approvable letter for the drug called Thelin, stating that Encysive’s development program did not demonstrate the evidence of effectiveness needed for approval.

Encysive said the FDA “encouraged the company to conduct an additional study” documenting that the drug improves exercise tolerance.

It is, indeed, bad news, especially, that in the same day, Gilead’s product was granted approval for the same disease.

TECHNOLOGIES ON THE ROAD TO VALIDATION

admin — Mon, 18 Jun 2007 16:45:58 +0000

DNA delivery technology (Vical) and rAAV Vctor Technology (Targeted Genetics)

VICAL’S DNA DELIVERY TECHNOLOGY

Vical (VICL) had licensed its its DNA delivery technology to the Japanese firm AnGes MG. This firm reported positive results on its drug candidate developed based on Viccal’s technology. The drug, HGF genetic uses Vical’s technology to deliver a gene encoding Hepatocyte Growth Factor (HGF), a human protein that causes angiogenesis (growth of blood vessels) in areas of ischemia (restricted blood flow).

Interim analysis of data from a Phase 3 trial on patients with critical limb ischemia (advanced peripheral arterial disease) demonstrate that the drug is safe and has achieved statistical significance with regard efficacy. As a result, an Independent Data Monitoring Committee (IDMC) recommended stopping the trial early to prevent potential ethical issues against the placebo group subjects. AnGes is ending the trial and preparing to file an application for Japanese marketing approval.

The results validate Vical’s DNA delivery technology.

TARGETED GENETICS’ rAAV VECTOR TECHNOLOGY

TARGETED GENETICS (TGEN’S) inflammatory arthritis drug tgAAC94 is a TNF modulator developed for intra-articular injection. The rationale behind this drug development is based on the fact that not all arthritis patients fully respond the approved systemic tumor necrosis factor-alpha (TNF-alpha) antagonists, which otherwise were tremendously effective in stopping the joint inflammation and progressive degeneration.

Obviously, Targeted Genetics drug tgAAC94 attempts to benefit those patients who have not been lucky with the systemically administered anti-TNF drugs such as Enbrel and Remicade. What encouraged Targeted Genetics to develop the drug is its recombinant (rAAV) vector technology, which made possible the development of an effective intra-articular TNF inhibitor version. The drug was tested in clinical trials and recently, some results began to emerge, suggesting good news.

Results: Data from the dose escalation arm of the ongoing Phase 1/2 clinical study of tgAAC94 on patients with inflammatory arthritis demonstrate that tgAAC94 is safe and provides clinical benefit to arthritis patients who are being treated with the marketed systemic TNF antagonists. At week 12 after treatment with tgAAC94, 13%, 14% and 33% of subjects receiving low, mid and high dose tgAAC94, respectively, achieved a two-point reduction in swelling compared to none who took placebo. A trend towards reduction of swelling was observed in tgAAC94-injected joints compared to placebo in subjects with or without concurrent use of systemic TNF antagonist.

According to the firm’s scientists, the data suggest that tgAAC94 has helped arthritis patients who have not fully benefited from the systemic TNF antagonists.

Targeted Genetics promised to present additional data that provide more insight into the most effective way to advance the development of tgAAC94. Further testing is currently being made with a follow up that enables further assessment of safety, improvement in swelling and functional improvement in the treated joints. MRI is planned on treated joints in a subset of subjects for image-based assessment.

Comments: Taking care of patients who do not benefit from the best arthritis treatments in town is necessary if feasible. It seems it is. The beneficial effect, if confirmed would touch the patients, the rheumatologists and Targeted Genetics. It validates its technology.

Like the firm, we are also encouraged by the results of Phase 1/2 trials and are anxious to learn more from the additional data that will be presented soon. If tgAAC94 passes the test, it will be a great validater of Targeted Genetics’ rAAV vector technology, which is used to deliver a DNA sequence that encodes a soluble form of the TNF-alpha receptor (TNFR:Fc).

This technology was originally developed to deliver genes for gene replacement. The concept proved to be working as the rAAV vector technology enabled the lintraarticularly injected tgAAC94 to instigate an intracellular secretion of TNFR:Fc within joints, preventing TNF alpha from causing joint inflammation and destruction. Adeno-associated virus (AAV) has never been associated with any disease in humans.

It is another validation of a relevant, but difficult technology that has taken a long time to provide results. We hope the results will be confirmed.