Cancer Therapy Center

NeoPharm Inc announced a restructuring of its workforce following a late failure of its brain cancer drug earlier this month. The drug, cintredekin besudotox, was slated to be the company’s first commercial product. The restructuring, which will result in 14 employees being dismissed, will save the company about $1.5M over the course of 2007.

The trial data showed that patients receiving cintredekin besudotox had roughly the same survival rate as patients receiving MGI Pharma’s Glidel Wafer treatment, the current industry standard. This resulted in the company suspending future trials, leading to a 73% drop in stock price since.

The company is currently working on liposome-based drugs to treat breast cancer, colorectal cancer, and other advanced tumors.

Reuters notes that Abraxis (maker of Abraxane) published interim data showing tumors were more responsive to Abraxane and patients showed fewer side effects than with competing drug Taxotere.

Interim analysis of the 300-patient Phase II trial showed that 61 percent to 72 percent of patients treated weekly with a low dose and high dose, respectively, of Abraxane responded to the drug, compared with 36 percent given Taxotere every three weeks, the company said.

A dose of Abraxane give once every three weeks resulted in a response rate of just 33 percent.

A Phase III trial is scheduled for the first half of 2007. Both drugs are forms of pacilataxel, developed with the goal of interfering with cancer cell growth.

Medpage has an article noting that breast cancer clinicians seem to be fine tuning their art, with a major decline in morality when using radiotherapy, chemotherapy, and Tamoxifen, an analysis of clinical trial evidence has shown.

The five-year update by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), presented at the San Antonio Breast Cancer Symposium here by epidemiologist Richard Peto, Ph.D., of the University of Oxford in England, held no surprises but confirmed that radiotherapy, chemotherapy combinations, and tamoxifen were steadily reducing disease mortality. 

 

Overall, said Dr. Peto, breast cancer mortality rates have been dropping worldwide since the late 1980s, likely because of effective treatments, early diagnosis by mammography, better adjuvant treatment, and better treatment for relapse.

While each individual treatment has only moderate success against breast cancer, the treatments combine to be increasingly effective.

CBS News has a story noting that RU-486’s progesterone-blocking ability helps prevent breast cancer in mice carrying a dangerous “cancer gene”, a new study shows. While RU-486 is not safe for long-term use, other progesterone-blocking drugs are on the way to treat women carrying the BRCA1 gene mutation, says UCI Professor Eva Y.H.P. Lee.

“To prevent cancer, many women who are BRCA1 carriers have very traumatic surgery — their ovaries and both breasts are removed,” Lee tells WebMD.

“Many of these women have asked us about clinical use of RU-486, but it would have too many side effects for prevention use,” she says. “However, I am happy to say that for the past three years there have been companies working on more appropriate anti-progesterone drugs.”

Lee and colleagues report their findings in the Dec. 1 issue of Science.

QUEBEC CITY, Nov. 27

PRNewswire-FirstCall

AEterna Zentaris Inc today disclosed additional positive top line Phase 1 results for its cytotoxic conjugate AN-152 in patients with gynaecological and breast cancers. Further data showed the compound’s good safety profile and established the maximum tolerated dose (MTD) at 267 mg/m(2) which will be the recommended dose for a Phase 2 trial. In addition to good safety data, the trial provided a hint of efficacy as disease stabilization and regression of lesions were observed at the 160 mg/m(2) and 267 mg/m(2) dose levels.

Dr. Jurgen Engel, Executive Vice President, Global R&D and Chief Operating Officer at AEterna Zentaris, stated, “This additional data provides further proof of concept that the chemical linkage of doxorubicin and the luteinizing hormone-releasing hormone part of the drug molecule is stable in human blood. Most importantly, we witnessed a good safety profile and a hint of efficacy enabling us to establish a suitable dose for further development of AN-152 in the treatment of various cancers.”

Gilles Gagnon, President and Chief Executive Officer at AEterna Zentaris added, “We are very pleased and now even more encouraged with the latest Phase 1 results for AN-152 which lend further credibility to our very promising oncology platform. By targeting patients suffering from ovarian and endometrial cancer with confirmed LHRH receptor status, we believe we may increase our chances of success for our Phase 2 program in these indications. This targeted approach is an additional example of personalized therapy which is becoming more and more the way of the future.”

About the AN-152 Phase 1 Trial in Gynaecological and Breast Cancers

This ongoing Phase 1 open-label, multi-center, dose-escalation, safety and pharmacokinetic study conducted in Europe, includes 17 patients suffering from breast, endometrial and ovarian cancers with proven luteinizing hormone-releasing hormone (LHRH) receptor status. Patients were administered AN-152 by intravenous infusion over two hours at dosages of 10, 20, 40, 80, 160 and 267 mg/m(2). Patients received at least two treatment courses, 21 days apart.

Results

Dose escalation was stopped at 267 mg/m(2), which is equimolar to a doxorubicin dose of 77 mg/m(2), and declared as maximum tolerated dose (MTD) due to dose-limiting although rapidly reversible hematoxicity (CTC grade 4 leucocytopenia/neutropenia) in two out of six patients. Pharmacokinetic (PK) analyses showed dose-dependent plasma levels of AN-152 and only minor (10%-30%) release of doxorubicin. One complete response (TBC by forthcoming CT scan) and two stable disease out of six patients at the 160 mg/m(2) dose level were reported, while at the 267 mg/ m(2) dose level, one partial response and three stable disease were observed from this group of seven patients.

Conclusion

Infusion of AN-152 is well tolerated in female patients. Disease stabilization and regression of lesions are promising signals for therapeutic activity of the cytotoxic LHRH analog, most probably through receptor-mediated uptake by tumor tissue. Because of the rapid reversibility of the potentially dose-limiting hematoxicity even in patients with multiple prior therapies, the dose of 267 mg/m(2) is going to be recommended for Phase 2 trials with ovarian and endometrial cancer as targeted indications. Ovarian and endometrial cancers are two forms of cancer where LHRH receptors are highly expressed.

Background

Human breast, endometrial and ovarian cancers commonly express receptors for luteinizing hormone-releasing hormone (LHRH-R). High-affinity binding sites for LHRH are found in 52% of human breast cancers, as well as in 80% of human ovarian and endometrial cancers. LHRH-R can be used for targeted chemotherapy with AN-152, in which doxorubicin is linked to (D-Lys(6))-LHRH. Safety pharmacology and toxicity studies in mice, rats and dogs demonstrated a significantly reduced cardiotoxic potential of AN-152 compared with doxorubicin, e.g. no QT prolongation, myocarditis or fibrosis in the appropriate models. The Phase 1 study assessed dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and pharmacokinetics (PK) of AN-152 given once every three weeks in patients with gynaecological and breast cancers.

About Cytotoxic Conjugate AN-152

Targeted cytotoxic peptide conjugates are hybrid molecules composed of a synthetic peptide carrier and a well-known cytotoxic product. The design of these products allows for the specific binding and selective uptake of the cytotoxic conjugates by the LHRH receptor-positive tumors. The binding of cytotoxic conjugates to cancerous cells that express these receptors results in an accumulation of the antiproliferative agent in the malignant tissue. This binding is followed by internalization and retention of the cytotoxic drug in the cells. Therefore, since they target specific cells, cytotoxic conjugates are much less toxic, have less side-effects and are more effective in vivo than the respective radicals in inhibiting tumor growth.

About AEterna Zentaris Inc.

AEterna Zentaris Inc. is a growing global biopharmaceutical company focused on endocrine therapy and oncology, with proven expertise in drug discovery, development and commercialization.

News releases and additional information are available at www.aeternazentaris.com.

Forward-Looking Statements

This press release contains forward-looking statements made pursuant to the safe harbor provisions of the U.S. Securities Litigation Reform Act of 1995. Forward-looking statements involve known and unknown risks and uncertainties, which could cause the Company’s actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of the Company to take advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. Investors should consult the Company’s quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned not to rely on these forward-looking statements. The Company does not undertake to update these forward-looking statements.

CBS News is one of many carrying the news about the FDA’s expanded approval of Herceptin for treating breast cancer.

The breast cancer drug Herceptin received expanded federal approval Thursday to include treatment of some women after they have undergone surgery.

In two clinical trials, women given the drug along with chemotherapy had fewer relapses in the three years after surgery — either to remove a lump or the whole breast — than those just given standard chemotherapy, the Food and Drug Administration said in announcing the additional approval. The drug is made by Genentech Inc. of South San Francisco, Calif.

In 1998, the FDA approved Herceptin to treat breast cancer after it had spread to other parts of the body. Thursday’s approval expands its use to women with cancer in the breast or lymph nodes that has been surgically removed, the FDA said.

Only patients with HER-2 positive tumors, and who do have heart failure or a weak heart, should be given the drug, also known as trastuzumab.

A warning is being recommended for certain post-menopausal women who use the drug tamoxifen to treat breast cancer. A federal health advisory panel says women carrying a variant of a certain gene face a greater risk of the cancer recurring when using Tamoxifen, and has recommended that its label be changed to warn patients and urge genetic testing.

The drug, which has been on the market for nearly 30 years, is used to treat beast cancer and as a preventative drug for women at risk. It was not immediately clear whether preventative usage in patients carrying the suspect gene would increase the likelihood of cancer occurrence.

NBC5 (Dallas) has an article about a new breast cancer therapy trial at USC:

Radiation treatment for breast cancer patients often drags on for weeks and comes with unpleasant side effects, but a new treatment in clinical trials aims to eliminate those problems.

The Targeted Intraoperative Radiotherapy Trial, or TARGIT, at the University of Southern California is testing intraoperative radiotherapy — a one-time, half-hour procedure that takes place in the operating room while doctors are removing the breast tumor.

There, radiation is delivered directly to breast tissue in a single dose.

“We know that breast cancer most commonly occurs where the original tumor was found, so the advantage of this treatment is that we can target the treatment to the part of the breast that needs the radiation the most,” breast surgeon Dr. Dennis Holmes.

“There’s no nausea, no long term changes. The skin looks almost as though it’s not radiated. So, the side effects are very minimal by comparison,” surgeon Dr. Melvin Silverstein said.

“I just went to sleep and woke up, and it was done,” patient Nancy Bushnell said. “And I was home, cooking dinner that night.”

If approved, this therapy could dramatically change post-surgery breast cancer treatment, eliminating weeks of discomfort.

Swiss pharmaceutical company Roche Holding AG asked the European Medicines Agency to approve its drug, Herceptin, as a treatment for advanced breast cancer, the International Herald Tribune reports.

The application is based on a study that showed that “the addition of Herceptin to hormonal therapy doubles the median progression-free survival,” the company said in a statement.

HER2-positive breast cancer, which affects 20 percent to 30 percent of women with breast cancer, is an aggressive form of the disease that requires special attention because the tumors are fast-growing and there is a higher likelihood of relapse.

“This combination offers a new treatment regimen for patients who suffer from a particularly aggressive form of breast cancer, and we are pleased to have been able to progress this application so quickly,” said Eduard Holdener, Global Head of Roche Pharma Development.

Sales of Herceptin are up significantly in the first half of 2006, and expanded approval could allow sales to increase even more.

A four year study and safety profile in nearly 5,000 patients confirmed that Femara® (letrozole tables) reduced the risk of breast cancer returning, even in higher risk patients.

Longer term data comparing two arms of the independent Breast International Group (BIG) 1-98 trial were presented at the European Society of Medical Oncology Congress in Istanbul by Dr. Alan Coates, M.D. Postmenopausal women with hormone-sensitive breast cancer taking Femara had an 18% reduction in their overall risk of recurrance and an 19% reduction in the risk of their cancer spreading to another part of the body. Also, Femara resulted in substantial risk reduction in women whose cancer had already spread to the lymph nodes at the time of diagnosis (risk of recurrence reduced by 23%), and those who had received chemotherapy (risk reduced by 26%).

“Longer-term data out to more than four years in 5,000 women provide the most compelling evidence to date that Femara helps to reduce breast cancer relapse in postmenopausal women,” said Diane Young, Vice President and Global Head of Clinical Development at Novartis Oncology. “We are committed to ongoing research that will help define optimal treatment for women with breast cancer.”

About Femara
Femara® (letrozole tablets) is a once-daily oral prescription medication approved for the adjuvant (following surgery) treatment of postmenopausal women with hormone-receptor positive early breast cancer. The benefits of Femara in clinical trials are based on 24 months of treatment. Further follow-up will be needed to determine long-term results, including safety and efficacy.

Femara is also approved for the extended adjuvant treatment of early stage breast cancer in postmenopausal women who are within three months of completion of five years of tamoxifen therapy. The benefits of Femara in the extended adjuvant setting are based on 24 months of treatment. Further follow-up will need to determine long-term results, including side effects.

Femara is also approved for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer. Femara is also indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy.