Biotech companies presented a wealth of data at the American Society of Clinical Oncology's annual meeting in Atlanta this weekend, but several pharmaceutical firms also shared their successes and disappointments.
In addition to the promising data on Tykerb in breast cancer (see today's story), London-based GlaxoSmithKline plc showed through a Phase III study that its cervical cancer vaccine candidate, Cervarix, is highly immunogenic and well tolerated. All of the women vaccinated with Cervarix demonstrated antibody response against HPV 16 and HPV 18 - the two most common types of human papillomavirus that cause cancer.
The trial included 666 women, ages 15 to 55, from Germany and Poland. Previous studies of cervical cancer vaccines have focused mainly on the younger populations.
Cervarix, which is expected to reach the market by 2007, could become a strong competitor of Whitehouse Station, N.J.-based Merck & Co. Inc.'s Gardasil, which is awaiting FDA approval, expected this week. An FDA committee has unanimously recommended approval of Gardasil, which analysts estimate could earn $1.6 billion or more in annual sales.
Merck also presented data at ASCO showing its histone deacetylase inhibitor, Zolinza (vorinostat), did well in a pivotal Phase IIb open-label study in which 30 percent of the patients (22 of 74) had an objective response.
Other pharmaceutical companies reporting data at ASCO included London-based AstraZeneca plc on Zactima in lung cancer and Arimidex in breast cancer; Indianapolis-based Eli Lilly and Co. on its metastatic breast cancer drug Alimta; Madison, N.J.-based Wyeth on Temsirolimus for advanced renal-cell carcinoma; Basel, Switzerland-based Novartis AG on Gleevec in chronic myeloid leukemia; and New York-based Bristol-Myers Squibb & Co. on its cancer drug, Dasatinib.
London-based Antisoma plc watched its shares (LSE:ASM) fall £3, or 12.9 percent on Monday, to close at £20.25 (US$37.92) after the company said it completed a Phase I trial of R1550, but lost a collaborator.
The safety study showed the drug was well tolerated at the maximum dose tested in metastatic breast cancer patients, a number of whom showed prolonged stabilization of disease. But Antisoma also said it was losing partner F. Hoffmann-La Roche Ltd., of Basel Switzerland, and will rename the drug AS1402 and move it into a Phase IIa study on its own.
Similarly, it said it regained all rights to AS1404 from Roche, but said it would move the drug into a Phase III trial in lung cancer.
In other news at ASCO:
• Abraxis BioScience Inc., of Los Angeles, said Phase II data of Abraxane for injectable suspension as a first-line treatment for late-stage non-small-cell lung cancer showed improved antitumor benefits over the solvent-based taxane treatment (Taxol). The data form the basis for the Phase III registration trial. They show that 50 percent of patients had either a complete or partial response, and an additional 36 percent had stable disease for at least 12 weeks resulting in a disease control rate of 86 percent. Median time to disease progression was 28 weeks.
• Active Biotech, of Lund, Sweden, said interim data from the ongoing Phase I study of Anyara to treat advanced non-small-cell lung cancer, renal-cell cancer and pancreatic cancer have determined a reproducible induction of the immunostimulatory cytokine interleukin-2 as a surrogate marker for T-lymphocyte activation.
• Adherex Technologies Inc., of Research Triangle Park, N.C., said Phase Ib data of ADH-1 showed the drug was well tolerated in all five doses tested, displayed predictable pharmacokinetics and demonstrated evidence of antitumor activity in three patients with advanced, therapy-resistant cancer, including one with an unconfirmed partial response and two with prolonged stable disease.
• Adventrx Pharmaceuticals Inc., of San Diego, said preliminary median overall survival was 459 days or about 15.1 months in a Phase II trial of CoFactor as a first-line treatment in combination with 5-fluorouracil in metastatic colorectal cancer. Historically, median overall survival of 5-FU plus leucovorin was determined to be 11.7 months. For the primary endpoint, objective tumor response exceeded the 25 percent target established for the trial.
• AEterna Zentaris Inc., of Quebec City, said Phase I data of AN-152 in patients with gynecological and breast cancers showed the compound has a good safety profile and no dose-limiting toxicities. The company also said its North American partner, Keryx Biopharmaceuticals Inc., of New York, disclosed positive data of perifosine in patients with advanced renal-cell carcinoma. Three of seven evaluable patients had a partial response, and an additional two patients achieved long-term stable disease, while the remaining two progressed.
• Amgen Inc., of Thousand Oaks, Calif., said interim Phase IIIb data from 196 patients suggested Aranesp (darbepoetin alfa) administered every three weeks with intravenous iron has the potential to enhance the effectiveness of increasing patient hemoglobin levels to the recommended target of greater than or equal to 11 g/dL and reducing the need for red blood cell transfusions in cancer patients with chemotherapy-induced anemia. The firm also disclosed interim results from two Phase II studies of panitumumab, an investigational fully human monoclonal antibody that targets the epidermal growth factor receptor. Results from both studies suggest that antitumor activity of panitumumab was independent of tumor EGFr expression levels in patients with metastatic colorectal cancer who have failed standard chemotherapy. Separately, Amgen entered a deal with Locus Pharmaceuticals Inc., of Blue Bell, Pa., whereby Locus will apply its proprietary computational technologies to design novel small-molecule compounds having activity against a target identified by Amgen. Financial terms were not disclosed.
• Antigenics Inc., of New York, said Phase III data of Oncophage (vitespen) in metastatic melanoma showed that patients who received at least 10 doses of vaccine experienced an extension in median survival of 29 percent, compared with those who received physician's choice. In a subset analysis, Oncophage was associated with a potentially clinically relevant benefit compared with physician's choice.
• Bioenvision Inc., of New York, said pivotal data from its non-randomized, Phase II study of Evoltra (clofarabine) showed that the compound achieved a substantially higher overall complete response rate and a longer median survival than the current standard of care in elderly, high-risk patients with acute myeloid leukemia who were considered unsuitable for intensive treatment. In addition, the higher response rates translated into a clear survival benefit for Evoltra-treated patients with the high-risk cytogenetic profile, with a median survival more than six months.
• Cabrellis Pharmaceuticals Corp., of San Diego, started a Phase II trial of its synthetic, next-generation anthracycline, Calsed (amburicin), in small-cell lung cancer. The study is designed to assess Calsed in reference to topotecan in the second-line treatment of patients with SCLC who previously responded to platinum-based chemotherapy. Clinical results of Calsed in relapsed or refractory SCLC demonstrated notably high response rates in patients, it said.
• Celgene Corp., of Summit, N.J., said Phase III data from a North American trial in previously treated multiple myeloma patients showed an overall survival (p<0.0001) of 29.6 months in addition to median time to disease progression (p<0.0001) of 11.1 months in patients receiving lenalidomide plus dexamethasone compared to those receiving dexamethasone plus placebo (20.2 months, and 4.7 months, respectively). Updated clinical data from a pivotal international Phase III trial indicated that median overall survival has not been reached compared to 20.6 months with dexamethasone plus placebo. Celgene also said that clinical data from a study with combination therapy lenalidomide, melphalan and prednisone in elderly newly diagnosed multiple myeloma patients showed a response with no further disease progressions observed, and event-free survival (p<0.001) after 9.6 months of follow-up. Finally, the company updated clinical data from an ongoing Phase III study of oral combination therapy thalidomide plus dexamethasone vs. dexamethasone alone as induction therapy for previously untreated multiple myeloma. It showed a statistically significant improvement in median time to disease progression in the thalidomide group compared to the placebo group.
• Cell Genesys Inc., of South San Francisco, offered an oral presentation on its Phase I dose-escalation trial of GM-CSF-gene transduced allogeneic prostate cancer cellular immunotherapy in combination with a fully human anti-CTLA-4 antibody (MDX-010, ipilimumab, from Medarex Inc., of Princeton, N.J.) in patients with metastatic hormone-refractory prostate cancer. Twelve patients have been treated to date, including six patients who received the combination therapy at the therapeutic doses currently being evaluated in both GVAX and ipilimumab Phase III trials. Antitumor activity has been observed in five of these six patients including reductions in prostate-specific antigen levels that are ongoing at two months or longer and qualify in all five patients as partial responses. Another oral presentation dealt with long-term follow-up data from a Phase II trial of GVAX immunotherapy for chronic myelogenous leukemia. A total of 19 CML patients with molecular evidence of persistent leukemia following at least one year of Gleevec (imatinib mesylate, Novartis AG, of Basel, Switzerland) therapy were treated with GVAX immunotherapy while continuing to receive Gleevec. Updated results show that the addition of GVAX immunotherapy to Gleevec therapy reduced persistent leukemic disease in 10 of 19 patients as demonstrated by a complete disappearance (five patients) or a greater than one log (90 percent) reduction (five patients) in bcr-abl, a validated genetic marker found on the leukemic cells.
• Cell Therapeutics Inc., of Seattle, reported findings from a composite analysis of the STELLAR 3 and 4 studies demonstrating that Xyotax (paclitaxel poliglumex) had a significant impact on survival in women compared to those on the control arms, while men had similar survival in both arms of the studies. In addition, Phase I data showed that weekly dosing of CT-2106 for three consecutive weeks every 28 days resulted in a dose intensity similar to that seen with dosing once every 21 days in 19 patients with advanced solid-tumor malignancies.
• Cytogen Corp., of Princeton, N.J., said Phase I interim results of Quadramet in combination with bortezomib in patients with multiple myeloma whose cancer has relapsed following prior treatment indicate the combination regimen was well tolerated at doses studied to date and demonstrated antitumor activity, with 50 percent of patients experiencing a response or achieving stable disease. Also, Phase II data of Quadramet indicate that when used in combination with docetaxel in patients with progressive hormone refractory prostate cancer and bone metastases, the therapy is well tolerated, provides pain palliation and demonstrates promising rates of clinical and biochemical responses.
• Cytokinetics Inc., of South San Francisco, said a Phase II trial of ispinesib in patients with metastatic colorectal cancer showed that the therapy did not manifest an objective response rate on the two schedules evaluated in heavily pretreated patients. Phase Ib data of the drug in combination with carboplatin showed a partial response in one patient with breast cancer. A total of 13 patients had a best response of stable disease with durations ranging from three to nine months. Phase I data of SB-743921 showed a median half-life of 29 hours, and disease stabilization, ranging from nine to 45 weeks, was observed in seven patients. It is being studied for non-Hodgkin's lymphoma, Hodgkin's disease and multiple myeloma.
• Genentech Inc., of South San Francisco, and OSI Pharmaceuticals Inc., of Melville, N.Y., said Phase II data in patients with recurrent or refractory non-small-cell lung cancer suggested that the addition of Avastin to either Tarceva or chemotherapy improved progression-free survival compared to chemotherapy alone. The study included 120 patients.
• Genta Inc., of Berkeley Heights, N.J., said Genasense (oblimersen sodium) injection data from a Phase III trial showed the therapy induced remissions that were associated with elimination of minimal residual disease. The results were assessed by flow cytometry when Genasense was combined with fludarabine plus cyclophosphamide or rituximab in patients with chronic lymphocytic leukemia.
• GTx Inc., of Memphis, Tenn., said Phase III data of Acapodene (toremifene citrate) in an 80-mg dose increased bone mineral density in prostate cancer patients on androgen deprivation therapy.
• ImClone Systems Inc., of New York, disclosed findings from a Southwest Oncology Group randomized Phase II trial with Erbitux (cetuximab), an IgG1 monoclonal antibody, in non-small-cell lung cancer. The trial was designed to select an Erbitux-chemotherapy regimen for future evaluation and use in a Phase III trial. A total of 225 untreated patients with advanced stage NSCLC, squamous and non-squamous cell, were enrolled and got either chemotherapy (paclitaxel plus carboplatin) plus Erbitux (n=106) or the same doses of chemotherapy followed by Erbitux (n=119). The primary endpoint was overall survival. Median survival was 10 months in the concurrent Erbitux treatment arm and 9 months in the consecutive Erbitux treatment arm. The concurrent regimen of chemotherapy and Erbitux met the study's criteria for continued evaluation. The company also disclosed Phase I data on two fully human, IgG1 monoclonal antibodies, IMC-1121B and IMC-11F8.
• Immunomedics Inc., of Morris Plains, N.J., said Phase I/II results of its humanized anti-CD20 monoclonal antibody in patients with non-Hodgkin's lymphoma demonstrated an overall objective response rate of 43 percent, with 17 percent of patients having a complete response. In follicular lymphoma, the overall response rate was 44 percent, with a complete response rate of 22 percent.
• Introgen Therapeutics Inc., of Austin, Texas, and their clinical collaborators have identified a set of prognostic indicators associated with high response rates and increased survival in Phase II trials of Advexin in patients with recurrent squamous-cell carcinoma of the head and neck. A molecular biomarker predictive of Advexin activity is abnormal p53 function detected in tumor tissues by a routine laboratory test. Advexin therapy was correlated with a statistically significant increase in median survival of 11 months, compared to only three months for patients without abnormal p53.
• Kosan Biosciences Inc., of Hayward, Calif., reported encouraging interim clinical data on KOS-862 and KOS-1584, the company's most advanced epothilone drug candidates. The company offered data from a Phase Ib dose-escalating trial of KOS-862 administered in combination with trastuzumab (Herceptin, South San Francisco-based Genentech Inc.) in patients with HER-2 metastatic breast cancer (measurable disease was not required at entry). Thirteen patients received weekly doses of KOS-862 (at 75, 80, or 100 mg/m2) in combination with Herceptin (at registered dose) after previously failing treatment with chemotherapy, and antitumor activity was observed in three patients, including one confirmed and one unconfirmed partial response, and one patient with a greater than 90 percent reduction in a tumor marker. In a Phase I trial of KOS-1584 as a single in patients with advanced solid tumors, patients got the drug weekly in dose escalations from 0.8 to 20 mg/m2. No dose-limiting toxicity has been observed. Indications of anti-tumor activity included a 13 percent tumor shrinkage in one patient with non-small-cell lung cancer and a 40 percent decrease in tumor marker in a patient with advanced highly refractory ovarian cancer. Kosan also provided data from three Phase I trials of its two heat-shock protein 90 inhibitors, KOS-953 and KOS-1022. The compounds are being developed in collaboration with F. Hoffman-La Roche Ltd., of Basel, Switzerland.
• Ligand Pharmaceuticals Inc., of San Diego, said results showed the potential benefit of Targretin therapy added to chemotherapy in a first-line setting, or as monotherapy in a third-line setting, in patients with non-small-cell lung cancer. Patients in the subgroups that benefited from Targretin the most (males, smokers, greater weight loss, stage IV disease) are among those with the poorest prognosis and have not found a benefit with other targeted therapies.
• Medarex Inc., of Princeton, N.J., said interim data based on median follow-up of 12 months of extended dosing with ipilimumab (MDX-010) indicated that the treatment regimen was generally well tolerated in 25 patients with resected stage IIIc or stage IV melanoma treated with the drug and a multi-peptide melanoma vaccine in the adjuvant setting. All patients have survived to date. Phase II data of ipilimumab in combination with docetaxel showed that three of 20 patients experienced decreases in PSA serum levels of more than 50 percent.
• Metabasis Therapeutics Inc., of San Diego, presented a poster on MB07133 in patients with unresectable hepatocellular carcinoma, providing data on the safety, tolerability and pharmacokinetics from a dose-escalation clinical trial the company has been conducting in patients with primary liver cancer. Preliminary information related to possible signs of drug activity were shown as well.
• Millennium Pharmaceuticals Inc., of Cambridge, Mass., said Phase II data showed a median survival of 11 months for patients with non-small-cell lung cancer treated with a Velcade-based regimen. The results compared favorably to the historic nine-month survival seen in past studies with a two-drug platin-based regimen, a current standard of care.
• Novacea Inc., of South San Francisco, featured DN-101 and AQ4N in several oral and poster presentations. DN-101 is being investigated in Novacea's ASCENT-2 Phase III trial in androgen-independent prostate cancer and AQ4N is scheduled to begin a Phase I/II study for aggressive brain tumors in the second half of this year.
• Ortho Biotech Products LP, of Raritan, N.J., said data show that 80,000 units of Procrit (Epoetin alfa) administered once every two weeks demonstrated comparable changes in hemoglobin levels and safety in treating chemotherapy-related anemia in patients with non-myeloid malignancies compared to 40,000 units of Procrit once weekly, the current recommended dosage.
• Oxigene Inc., of Waltham, Mass., said Phase II data from two trials show patient response and biological activity of CA4P (Combretastatin A4 Phosphate) when it is used either in combination with chemotherapy or as a monotherapy. Treatment resulted in stabilized disease in one patient and a partial response in a second patient with anaplastic thyroid carcinoma. Analysis of blood flow volume to the tumors showed a statistically significant and sizeable reduction of more than 73 percent for both patients.
• Pharmion Corp., of Boulder, Colo., said data demonstrated that the addition of thalidomide to standard therapy improved overall survival in patients with newly diagnosed multiple myeloma. The study was designed to compare overall survival in patients receiving standard therapy of melphalan and prednisolone, or standard therapy plus thalidomide or a combination of chemotherapy followed by melphalan and transplantation. A total of 447 patients were randomized to one of the three treatment arms. Pharmion also said Phase I/II data of Vidaza (azacitidine for injectable suspension) in patients with myelodysplastic syndromes and acute myelogenous leukemia demonstrated an overall response rate of 30 percent among 13 patients who completed one course of treatment.
• Seattle Genetics Inc., of Bothell, Wash., said Phase I data of SGN-40 in non-Hodgkin's lymphoma showed the therapy induced objective responses in five patients and was well tolerated at doses up to 8 mg/kg. The company is completing treatment of the final cohort of patients and plans to advance SGN-40 into Phase II trials during the second half of the year.
• Sunesis Pharmaceuticals Inc., of South San Francisco, said Phase I data of SNS-595 in patients with advanced solid malignancies showed the therapy exhibited clinical activity across a variety of tumor types among end-stage refractory patient populations. It was well tolerated with manageable side effects.
• Vion Pharmaceuticals Inc., of New Haven, Conn., said Phase II data of Cloretazine in elderly patients with de novo acute myelogenous leukemia showed a 50 percent overall response rate in the 44 de novo AML patients, 20 complete responses and two complete responses with incomplete platelet recovery. Cloretazine was well tolerated.
• Ziopharm Oncology Inc., of New York, said preliminary Phase I data support its premise that certain adverse events associated with ifosfamide, a cancer drug approved in the U.S. and Europe, can be avoided with ZIO-201, the active metabolite of ifosfamide. ZIO-201's maximum tolerated dose was shown to be about 1.5 g/me2/cycle, equivalent to 15 to 30 g/me2/cycle of ifosfamide, though it is rarely given at such a level because of substantial bladder and central nervous system toxicity, which were not evident with ZIO-201.
• ZymoGenetics Inc., of Seattle, said Phase I findings showed that the administration in an outpatient setting of interleukin-21 (IL-21) in patients with stage IV metastatic melanoma and renal-cell carcinoma was associated with a satisfactory toxicity profile and exhibited preliminary evidence of antitumor activity.