cafepharma’s detailpiece

At the Wachovia Healthcare Conference, yesterday, Celgene (NASDQ: CELG)CFO, Dave Gryska, delivered good news for Celgene investors and patients. The company is generating significant cash flows (900 million) and generated $1.4 billion in total revenue. This exceeded guidance at the beginning of ‘07 projecting $1.3 billion. Additionally earnings per share (EPS) for ‘07 of $1.06 will exceed guidance of $1.00.

The success of Revlimid was a major contributor to the attractive revenue and cash flows. Additionally, Celgene has completed a build out of capabilities in Europe that should begin generating returns in 2008, and they expect to close the acquisition of Pharmion in March of ’08. The transaction has already cleared regulatory hurdles in the U.S. and Europe.

It looks like 2008 will be another good year for Revlimid. It was approved for myelodysplastic syndromes (MDS) and multiple myeloma (MM) in Australia. Canada also approved Revlimid for MDS. Additionally, the company will present new Revlimid data in 2008 that is expected to expand Revlimid labeling and use.

Data from a study in newly diagnosed MM patients shows that Revlimid slows time to progression and some patients were progression free. There were also encouraging partial and total response rates.

A study recently published in the New England Journal of Medicine, reports that the median overall survival time is up to 35 months. The overall message from the studies is that patients on Revlimid are living longer, with better quality of life and Revlimid is delivered via a more attractive oral pill form vs. infusion/injection, etc.

Celgene believes that Revlimid is the top selling drug for MM in the U.S. for first year post launch. They expect that it will be overall market leader in the U.S. for 2008.

The potential market for Revlimid is very large. There are 300,000 MM and MDS patients in the U.S. and Europe combined. When all of the potential treatment approvals are considered, the potential patient population for the U.S., Europe, and Japan, is 1.5 million. By capturing only a part of this market, Revlimid would become a multi billion-dollar drug. 

While Revlimid is the company’s current growth engine, they also have a pipeline that includes additional products in the oncology/hematology arena and in the inflammation, psoriasis markets. Several of these therapies are already in phase II trials.

One of these is CC-4047. CC-4047 is a more potent Imid than Revlimid. It has a multi-factorial mechanism of action that includes, angiogneisis inhibition, modulation of levels of key pro-inflammatory and regulatory cytokines, and immune cell co-stimulation (e.g., T cells, NK cells).

Another promising candidate is CC-10004. This drug is in Phase II trials for the treatment of psoriasis and other chronic inflammatory diseases. Early studies demonstrated an excellent side effect profile and significant activity in psoriasis patients. The drug is more attractive than some current biologic (it is not a biologic) treatments because it is taken in pill form.

2008 should be an exciting year for Celgene and its investors. Although the integrating a new company (Pharmion) always leads to some disruption and friction, the company is poised to reap rewards from investments in Europe and Japan and to possibly expand labeling and patient base for Revlimid. While drug development is always a gamble (even in late stages), Celgene’s experience in bringing novel drugs to market gives it an advantage in developing a very promising pipeline.

At the Wachovia Healthcare Conference yesterday, OSI Pharmaceuticals (NASDAQ: OSIP) discussed Tarceva sales and future plans and strategies. OSI is predicting $2.00 EPS (earnings per share) for 2008 based on the strength of Tarceva sales. This is up from approximately $1.15 EPS for 2007.

Tarceva sales for Q4 2007 were $250 million and tracking at $1 billion annually. The company thinks Tarceva sales will only increase in the future. Additionally the company will be able to shield significant future income via $1 billion dollars in loss accumulated prior to bringing Tarceva to market.

The next target for Tarceva sales is the $2 billion mark. The company feels this can be obtained with no additional cost.

Tarceva is positioned to be a growth engine for some time into the future. Several studies that should yield some results in 2008 have the potential to increase Tarceva’s patient base and sales. The Saturn Study, which is examining the use of Tarceva as maintenance therapy in non-small cell lung cancer patients could result in a doubling of Tarceva’s patient base. The BETA-lung trial is evaluating the use of Tarceva with Avastin as a second line therapy in advanced non-small cell lung cancer. Additional studies should yield data in 2010 (in ovarian cancer) and 2014. Data from these studies could drive additional growth in Tarceva sales into its advanced life cycle stages.

While the spokesperson did not address patent strategy, he did mention that Tarceva should still have significant patent life in 2014. The competitive landscape also bodes well for Tarceva at the moment.

In the last 18 months, eight of nine studies in lung and pancreatic cancer have failed to meet their primary endpoints. At this time, the company does not foresee a competitive threat to their pancreatic treatment. In fact, the spokesperson said they feel the competitive landscape to be “de-risked” at this point. 

While Tarceva is the current primary revenue engine, OSI is developing a number of promising therapies. Their strategy is to focus on treatments that will be either first in class or best in class and to abandon those that do not have that potential. They expect data on OSI-906 (a possible treatment for variety of human cancers, including colorectal, non-small cell lung, breast and ovarian cancers) in next 18 months. Data from studies involving OSI-027 (a kinase inhibitor that inhibits the kinase activity associated with both the TORC1 and TORC2 complexes of mTOR) should yield data in first half of 09.

OSI seems to be positioned for continued growth into the future. Their focus on financial discipline (they recently reduced head count to 2005 levels) and developing Tarceva should provide ample resources for developing their early but promising pipeline.

At the Wachovia Securities Healthcare Conference, Onyx Pharmaceuticals (NASDAQ: ONXX) presented recent financial results and information regarding ongoing studies for its lead product, Nexavar. Juliana Woods, VP of Investor Relations discussed financial performance and overall development programs. Henry Fuchs, M.D., discussed clinical trials in more detail. The presentation can be heard in its entirety at: http://www.wsw.com/webcast/wa48.

Nexavar has been approved in the EU and the US for liver cancer and it has been approved in more than 60 countries for kidney cancer. Nexavar has been shown to have a dual effect on cancer via inhibition of members of two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply).  Its proven success in prolonging survival times in patients with liver and renal cancer and its ease of administration (it is taken orally by pill in the patient’s home) has led to accelerating revenue growth.

For the first three quarters in 2007, net sales of Nexavar have grown approximately 20 million per quarter (247 million in overall sales for the first nine months of 2007). Onyx is conducting numerous studies to expand usage and maximize the potential of Nexavar. Dr Fuchs mentioned one researcher’s promising finding using twice the labeled dose of Nexavar in kidney cancer patients. The increased dose was tolerated by most of the patients and led to remission in a number of patients with complete remission in some. Dr Fuchs said that there are efforts under way to study this dose and replicate its results in other clinics.

There are clinical studies underway in additional liver cancer regimens, breast cancer, and melanoma. If Nexavar can replicate its ability to prolong survival times in metastatic breast cancer and melanoma patients, Onyx should see significantly increased revenues. In the U.S. Onyx co-promotes Nexavar with Bayer. Bayer has full promotion rights outside of the U.S.

The Onyx team did not address Nexavar’s patent protection strategy or expected patent lifespan. They did point out that Nexavar is the only systemic drug approved for liver cancer in the U.S. However, bio-similars are already an issue in the E.U. and will become more of an issue in the U.S.

Should Nexavar prove to be as successful in improving treatment options in other cancers as it has been in liver and kidney cancer, both patients and investors will benefit.

XenoPort, Inc. (Nasdaq:XNPT) and GlaxoSmithKline (NYSE:GSK) today announced positive top-line results from a Phase 3 clinical trial designed to evaluate the potential of XP13512 (GSK1838262) to maintain efficacy over the course of nine months in patients with moderate-to-severe primary Restless Legs Syndrome, (RLS). The study showed that XP13512 was generally well tolerated and that there was a statistically significant difference between patients treated with XP13512 and placebo who met study met study inclusion criteria.

The CEO of Xenoport said, “The results of this study strengthen our belief that XP13512 has the potential to be a safe and effective treatment for primary RLS. Our first placebo-controlled Phase 3 efficacy trial of XP13512, with results announced in April 2007, demonstrated statistically significant benefits of XP13512 in treating RLS symptoms over 12 weeks. We are encouraged by the results of this new placebo-controlled Phase 3 clinical trial, which demonstrated that XP13512 was effective and generally well-tolerated when administered to primary RLS patients for nine months,”

XP13512 is a patented, new chemical entity that is designed to improve the clinical utility of gabapentin by utilizing high-capacity transport mechanisms in the gastrointestinal tract to improve absorption.  Currently, doses of gabapentin greater than 1,200mg are poorly absorbed due to transport mechanisms in the gut being overloaded.  This new technology may show promise in achieving higher blood levels of gabapentin for RLS and many other conditions in which gabapentin is used frequently (i.e. psychiatry, pain, headaches).

RLS affects up to 12 million people in the U.S. according to the National Institutes of Health. RLS is characterized by unpleasant and sometimes painful sensations in the legs hat result in a compelling urge to move. Data suggests that RLS can have an impact on quality of life that is equal to or worse than major chronic disorders such as diabetes and osteoarthritis.

Seattle Genetics (Nasdq: SGEN)announced today that it intends to sell, subject to market and other conditions, 10,000,000 shares of its common stock in an underwritten public offering. The underwriters will be granted a 30-day option to purchase up to an additional 1,500,000 shares of the common stock to cover over-allotments.

Information about the offering is available in the prospectus supplement filed with the SEC. Copies of the prospectus can be obtained from J.P. Morgan’s prospectus dept at 4 Chase Metrotech Center, CS Level, Brooklyn, NY 11245, Attention: Prospectus Department and from UBS Investment Bank, Attention, Prospectus Department, 299 Park Avenue, New York, NY 10171 or 888-827-7275.

The company has filed a shelf registration relating to the securities being offered with the SEC.

Seattle Genetics is a clinical stage biotech company that is focused on the development and commercialization of monoclonal antibody-based therapies for cancer and autoimmune diseases.

Mochida Pharmaceutical announced today that it has liscenced a portfolio of transient receptor potential vanillion sub type 1 (TRPV1) receptor antagonists - to Wyeth (NYSE: WYE) as a potential novel treatment for pain.   Other potential uses for TRPV1 antagonists currently under investigation include cough and appetite stimulation (Neurogen Corp. & Glaxo SmithKline)

Wyeth will obtain exclusive worldwide rights to develop, manufacture, and use and sell therapeutic agents containing (TRPV1). Mochida will receive an upfront payment and potential milestone payments and royalties based on sales.

Mochida retains the right to co-develop and co-promote such drugs in Japan.

TRPV1 is a receptor and ion channel, which is stimulated by various stimuli including capsaicin (pungent ingredient contained in chili pepper also called substance P). It is expressed in sensory neurons and pain pathways following a noxious event. The companies hope that TRPV1 will be efficacious in treating pain resulting from inflammation or neuropathy without causing the gastrointestinal or renal side effects sometimes associated with existing painkillers.

Several other pharmaceutical companies are engaged in similar research involving the TRPV1 receptor. Recently positive phase-I clinical data has been published by GSK to support this proof of concept.

Pharmion Corporation (Nasdaq: PHRM) and MethylGene Inc. (pink sheets: MYLGF.pk) announced the enrollment of the first patient in a Phase 2 clinical trial (Trial CL002) evaluating MGCD0103. This is the Companies’ isotype-selective histone deacetylase inhibitor (HDACi) product candidate. It will be used in combination with Vidaza (azacitidine for injection), Pharmion’s DNA demethylating agent in patients with relapsed of refractory Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL).

Key objectives of the study will be to determine the overall response rate, progression free survival and duration of response. Up to 75 patients will be enrolled in North America.

Pharmion’s executive vice president and chief medical officer, Andrew Allen, said that, “The biology of cancer suggests multiple epigenetic mechanisms cooperate to silence tumor suppressor genes, which raises the simple hypothesis that attacking these mechanisms with drug combinations may be superior to single-agent therapy. In this trial, we are combining Vidaza, our DNA methyltransferase inhibitor, with MGCD0103, our isotype-selective HDAC inhibitor, in a clinical study of this therapeutic approach. We are unique in our ability to conduct a trial like this, using drugs from our own portfolio.”

MGCD0103 has demonstrated encouraging anti-tumor activity as a singly agent in a Phase 2 clinical study in relapsed or refractory Hodgkin lymphoma patients. Data reported an objective complete and partial response rate of 38 percent and a disease control rate of 43 percent in 21 experiencin a tumor reduction of greater than 30 percent. The two complete response patients have a preliminary progression-free survival of 14 and 9 months at the time of the analysis. Adverse events experienced with MGCD0103 administration grade 3 or higher included pneumonia (15%), thrombocytopenia (12%) and fatigue (9%). Dose modification was effective in many of these patients.

MGCD0103 is an orally-administered, isotype-selective HDAC inhibitor. It is currently in one Phase 1 combination clinical trial with Taxotere for solid tumors, and two Phase 1/2 combination trials with Vidaza for hematological malignancies and with Gemzar for pancreatic cancer; and five Phase 2 clinical trials in hematological malignancies.

MGCD0103 has received orphan drug designation by the FDA and has been designated an orphan medicinal product by the European Medicines Agency for the treatment of Hodgkin Lymphoma.

According to an article on the National Legislative Association on Prescription Drug Prices (NLARx) website, its Chair and Council member, David Catania, was recently named Big Pharma Enemy Number 1. The article states this fact as if it were an official designation like the FBI’s public enemy number 1.

I have been in the pharmaceutical industry for over a decade and still I am surprised to hear of the list. I wonder if some of my colleagues were chosen to become part of a secret hit squad that terminated big pharma enemies. Maybe the sweet smiles of some of the so-called pharma barbies hide a more sinister intent than simply encouraging gaga Drs to write expensive medications for patients that the patients don’t really need. I guess I will never know for sure.

In actuality, the designation comes from another website called bigpharmarealpeople.org  This site does not seem to be related to any pharmaceutical company or organization. In other words the designation means nothing. While the NLARx article does link to the bigpharmarealpeople website for the complete article, it makes no attempt to clarify the fact that the title is essentially made up and has no meaning reality.

Morphotek, Inc a subsidiary of Eisai Co, Ltd, announced today that is has signed a Cooperative Research and Development Agreement (CRDA) with the National Cancer Institute (NCI) for the development of therapeutic antibodies to a cancer-associated protein identified by NCI researchers. Morphotek’s proprietary MORPHODOMA(R) antibody technology will be used to develop novel antibodies for use in the treatment of prostate cancer. NCI will contribute its expertise in evaluating lead candidates for development.
NCI researchers have discovered several proteins whose expression is prostate specific. One of these proteins ProCa-1 is a gene product that is expressed on the surface of both normal prostate cells and prostate cancer cells. It is not expressed in other tissues tested. Morphotek will apply its antibody discovery platform to the development of monoclonal antibodies (mABs) that can bind the ProCa-1 and test lead mAB candidates for anti-cancer properties with NCI researchers.

Nektar Therapeutics (NASDAQ: NKTR) announced the start of its Phase 2 clinical development program to evaluate NKTR-102 (PEG-irinotecan) as a potential treatment for colorectal cancer. The molecule is the lead candidate developed with the company’s small molecule PEGylation technology platform.

Nektar President and CEO, Howard Robin said, “The start of the Phase 2 program for NKTR-102 in colorectal cancer is a major achievement for Nektar. Our Phase 2 program has the potential to demonstrate Nektar’s ability to generate innovative and important PEGylated small molecule therapeutics. Based on our positive Phase 1 study findings, we also plan to initiate Phase 2 studies this year to evaluate NKTR-102 in multiple solid tumor settings”.

Results from the Phase 1 study for NKTR-102 will likely be presented at major oncology conferences in 2008.

The first study in the Phase 2 program will investigate NKTR-102 in combination with cetuximab as a second-line treatment for colorectal cancer in irinotecan-naive patients as compared to treatment with standard irinotecan in combination with cetuximab.

The colorectal study will have 2 stages. Phase 2a is an open-label, dose-finding trial in multiple solid tumor types that have not responded to standard curative or palliative therapies. The Phase 2b trial is an open-label, randomized, double-arm study in patients with second-line metastatic colorectal cancer. Phase 2b is expected to begin in the middle of 2008 and will be conducted in over 40 centers worldwide. The primary endpoint of the 2b trial is progression-free survival. Secondary endpoints include response rate, response duration, overall survival, standard pharmacokinetics and incidence of toxicities, including diarrhea and neutropenia.

Nektar Therapeutics is a biopharmaceutical company that develops and enables therapeutics based on its PEGylation and pulmonary drug development platforms. Nektar technology has been employed in the development of nine approved products for Nektar partners. Additionally, Nektar develops its own products by applying its platforms to existing drugs to improve efficacy, safety and compliance.