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Biotechnol Healthc. 2010 Winter; 7(4): 6–7.
PMCID: PMC3008391

Clinical Trials, Research, and FDA Actions

Amy Krajacic, Senior Editor

Late-stage cancer trials

Two trials of brentuximab vedotin, an antibody/chemotherapy combination developed by Seattle Genetics and Takeda Pharmaceutical, have produced positive outcomes. In a pivotal trial, tumors shrank in 75 percent of 102 patients with Hodgkin’s lymphoma, and in a mid-stage trial, 86 percent of 58 patients with anaplastic large cell lymphoma also responded to treatment. The drug aims to bolster chemotherapy’s effectiveness while limiting its side effects — brentuximab vedotin is attached to an antibody so that the drug homes in on the cancer and kills it, but it does not affect harmless cells.

Genentech/Roche reported successful treatment outcomes with trastuzumab-DM1, which combines a maytansine derivative with trastuzumab (Herceptin). In a 6-month trial, tumors shrank in 48 percent of women with HER2-positive breast cancer, compared with a 41 percent response rate in women who received standard treatment of trastuzumab and docetaxel. About 50 percent fewer women given trastuzumab-DM1 experienced serious adverse effects compared with the standard therapy group. The results were reported at the European Society for Medical Oncology congress 5 weeks after the FDA denied a bid for accelerated approval based on results of a successful phase 2 trial (see Denials and Delays in table, page 7). Phase 3 trials will continue, and the manufacturer now hopes to submit a biologics license application in 2012.

At the same conference, a British team reported that bevacizumab (Avastin) in combination with paclitaxel and carboplatin chemotherapy extended progression-free survival (PFS) by 1.7 months in women with ovarian cancer compared with patients given chemotherapy alone. The benefit seemed to peak after 1 year, however, and after 2 years, PFS was actually lower in the bevacizumab group.

Results of two trials of panitumumab (Vectibix) in combination with chemotherapy regimens showed statistically significant PFS increases in patients with metastatic colorectal cancer (mCRC). In the PRIME 203 study, median PFS increased by 1.6 months in patients given a combination of panitumumab and FOLFOX, an oxaliplatin-based chemotherapy, as first-line treatment compared with patients receiving FOLFOX alone. In the PRIME 181 study, median PFS increased 2 months in patients treated with panitumumab and FOLFIRI, an irinotecan-based regimen, as second-line treatment compared with patients given FOLFIRI alone. Currently, panitumumab is indicated as a last-resort monotherapy for mCRC patients after chemotherapy regimens have failed.

Trial disappointments

AstraZeneca’s zibotentan, a potential prostate cancer treatment, failed one of three clinical trials for the treatment of men with meta-static castration-resistant prostate cancer. The agent did not achieve a significant improvement in overall survival, and AstraZeneca has no plans for regulatory submission.

Eli Lilly & Co. and MacroGenics will suspend studies on their diabetes drug teplizumab after an independent panel of researchers found that the drug failed to slow the progression of type 1 diabetes in affected patients. Other possible treatment options for the drug are being considered.

Other research

Five-year follow-up data on a mid-stage trial of Genzyme’s alemtuzumab (Campath), an investigation agent for the treatment of multiple sclerosis, continued to show strong efficacy results. Eighty-seven percent of patients who received the drug experienced no worsening of their disability, and this figure was up from the 71 percent rate seen in the 4-year follow-up data. The data were presented at the European Committee for Treatment and Research in Multiple Sclerosis.

In a phase 2 multicenter clinical trial, AstraZeneca’s oral agent fostamatinib, given in conjuction with methotrexate (MTX), delivered significant improvement after six months of treatment to patients with rheumatoid arthritis. The trial enrolled 457 RA patients who either received 100 mg fostamatinib and MTX twice a day, 150 mg fostamatinib and MTX once per day, or placebo and MTX. Both doses were more effective than placebo and MTX, with 43 percent of the patients who received a combination of the active drug experiencing at least a 50 percent reduction in tendon and swollen joints versus 10 percent in the placebo group. Fostamatinib is a spleen tyrosine kinase inhibitor that works on a cellular level to block particular pathways responsible for joint inflammation.

Action dateManufacturerDrug (trade name)IndicationAdministration
New drug approval
Sept. 21Novartisfingolimod (Gilenya)Relapsing forms of multiple sclerosisOral (capsules)
New indications
Oct. 20Genentechtrastuzumab (Herceptin)HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinomaIntravenous infusion
SELECTED FDA ACTIONS, AUG. 16, 2010–OCT. 31, 2010
ManufacturerDrug (trade ame)Type of drugIndication soughtNotes
Fast-track designations
AstraZenecavandetanib (Zactima)Oral vascular endothelial growth factor receptor 2 blockerTreatment of medullary thyroid cancerIn a phase 3 study of 331 patients with advanced medullary thyroid cancer, those treated with vandetanib had a 54 percent reduced risk of progression to thyroid cancer.
iCo TherapeuticsiCo-009Oral amphotericin BTreatment of visceral leishmaniasisIf left untreated, fatality rate can reach 100% within 2 years.
Denials or delays
ImmunoGen and Roche/Genentechtrastuzumab-DM1Antibody drug conjugateTreatment of metastatic breast cancerFDA concluded that the data supporting trastuzumab-DM1 did not meet the BLA standard for accelerated approval because all available treatment choices had not been exhausted.
Teva Pharmaceutical Industriesfilgrastim (Neutroval)Generic version of Amgen’s NeupogenTreatment of neutropeniaFDA sought additional information but did not request a new trial. Teva wants to launch neutroval as its first biosimilar in the United States.

BLA = biologics license application.

Sources: Manufacturers’ news releases, FierceBiotech, BIO SmartBrief, wire reports, and weblogs

Two investigational agents have shown promise in the treatment of psoriasis. Pfizer’s oral drug CP-690,550 (tasocitinib) met its main efficacy goal in a mid-stage trial. A phase 3 trial is currently enrolling patients. In a phase 1/2a study, Novartis’ secukinumab, a novel agent that inhibits interleukin-17A, reduced scaly skin patches and lowered the production of inflammatory proteins. Investigators hope that seculinumab may also prove useful in the treatment of RA, uveitis, psoriatic arthritis, and ankylosing spondylitis.

Did you hear?

The National Cancer Institute has awarded a $2.5 million grant to Thomas Jefferson University to study imaging techniques that can detect activation of the KRAS2 gene in patients with lung cancer. Eric Wickstrom, PhD, professor of biochemistry and molecular biology at Jefferson Medical College and a member of the Biotechnology Healthcare editorial board, is the lead investigator.

Researchers have developed a “functional protein” microarray to help detect autoantibodies in prostate cancer serum samples that may precede disease symptoms by years. Investigators at Oxford Gene Technology, whose work was reported at the fourth American Association for Cancer Research (AACR) International Conference on Molecular Diagnostics in Cancer Therapeutic Development, hope that the biomarker may one day provide a diagnostic test to identify patients in presymptomatic stages of the disease.

Articles from Biotechnology Healthcare are provided here courtesy of MediMedia, USA