Avigen Inc. provided information showing progress in clinical testing of its Coagulin-B gene therapy for the treatment of hemophilia B at the American Society of Hematology's 42nd annual meeting at San Francisco's Moscone Center.
Coagulin-B is Avigen's proprietary adeno-associated virus vector. It carries the gene for factor IX, the missing or deficient protein that causes hemophilia B. Coagulin-B is designed to deliver the Factor IX gene into the patient's muscle or liver cells where it will continuously produce Factor IX.
The study is the first in gene therapy to report the long-term expression of a coagulation protein in humans, said Avigen, which submitted an investigational new drug application to assess, in a parallel clinical trial, the effectiveness of the product when delivered to the liver of patients. Coagulin-B is currently administered through intramuscular injection and both forms of delivery are being evaluated for a future Phase III pivotal study.
Avigen's stock (NASDAQ:AVGN) dropped $6.875 Monday, or 19 percent, to close at $29.50.
In other news from the ASH meeting:
¿ Alexion Pharmaceuticals Inc., of New Haven, Conn., presented preclinical results suggesting its C5 inhibitor may substantially prevent clotting complications associated with certain autoimmune disorders such as lupus, immune thrombocytopenia purpura and thrombocytopenic purpura. In the studies of spontaneous rodent models, administration of the C5 inhibitor prevented the severe thrombocytopenia (abnormally low platelet level) and subsequent elevation of immature reticulated platelets found in placebo-treated subjects.
¿ Amgen Inc., of Thousand Oaks, Calif., said Aranesp (darbepoetin alfa) appeared to be effective given just once every three weeks to anemic patients with solid tumors. Current standard of care requires injections three times weekly, although some patients are receiving weekly injections. Four doses were studied in a double-blind, placebo-controlled, Phase I/II study of 163 patients. In a second study, a dose-dependent relationship was seen between Aranesp given weekly and both hemoglobin increases and a reduced need for red blood cell transfusions.
¿ Ariad Pharmaceuticals Inc., of Cambridge, Mass., said results of a Phase II study of a first-generation graft-vs.-host disease treatment demonstrated the efficacy of regulated lymphocyte elimination as a treatment strategy following allogeneic bone marrow transplantation. The treatment involved infusion of donor T lymphocytes engineered with a gene encoding a herpes simplex virus thymidine kinase (HSV-tk). The engineered cells were programmed to die in vivo when the antiviral drug ganciclovir was administered to activate the HSV-tk gene.
¿ Aronex Pharmaceuticals Inc., of The Woodlands, Texas, presented preliminary Phase II clinical and pharmacokinetic data for Atragen, a liposomal, intravenous formulation of all-trans-retinoic acid. The preliminary data appear to support Atragen as a treatment for relapsed or refractory non-Hodgkin's lymphoma patients.
¿ Aventis Behring LLC, of King of Prussia, Pa., and Medarex Inc., of Princeton, N.J., presented positive results from a Phase II trial of MDX-33 for idiopathic thrombocytopenia purpura (ITP). The data suggested MDX-33 was well tolerated in subjects with chronic ITP, and a single dose of MDX-33 appeared to elevate platelet counts in all patients treated with the optimal dose. MDX-33 is a humanized monoclonal antibody.
¿ Celgene Corp., of Warren, N.J., said researchers presented data on clinical trials evaluating the safety and efficacy of Thalomid as a single agent and in combination treatment for multiple myeloma. Sol Barer, president and chief operating officer of Celgene, said the trial expands the knowledge base of Thalomid and Celgene intends to submit a supplemental new drug application in 2001. Thalomid received FDA clearance in 1998 for the acute treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum and as maintenance therapy for prevention and suppression of cutaneous manifestation recurrences.
¿ Cerus Corp., of Concord, Calif., and Baxter Healthcare Corp., of Deerfield, Ill., reported interim data supporting the safety and efficacy of the Intercept Plasma System from their Phase IIIa trial. The data showed it was well tolerated among the first nine patients. Data also were reported from a preclinical study showing the system was capable of inactivating high levels of hepatitis B and hepatitis C viruses in plasma.
¿ Corvas International Inc., of San Diego, gave final results from a Phase II trial on recombinant Nematode Anticoagulant Protein c2 (rNAPc2). Data showed, in the largest cohort, rNAPc2 reduced the risk of developing deep-vein thrombosis by greater than 50 percent compared to a historical control of low-molecular-weight heparin, the standard of care.
¿ Coulter Pharmaceutical Inc., of South San Francisco, and SmithKline Beecham plc, of London, presented results from a study on Bexxar in low-grade and transferred low-grade non-Hodgkin's lymphoma patients who failed to respond to, or progressed, following rituximab treatment. Bexxar produced a 70 percent overall response rate and a 40 percent complete response rate in patients previously treated with rituximab. In a separate presentation, Bexxar achieved a 35 percent complete response rate lasting a median of more than three years. The biologics license application for Bexxar was received by the FDA in September.
¿ Dendreon Corp., of Seattle, presented long-term follow-up data from the Phase II trials of its therapeutic vaccine, Mylovenge. The trials, involving patients with multiple myeloma and amyloidosis, indicated that Mylovenge causes regression or stabilization in more than 30 percent of patients. Mylovenge is designed to trigger the body's immune system to recognize and destroy cancer cells.
¿ F. Hoffmann-La Roche Ltd., of Basel, Switzerland, gave positive interim results from a Phase III study evaluating the combination use of MabThera (rituximab) and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy in previously untreated patients with aggressive non-Hodgkin's lymphoma. Results from the interim analysis of 328 patients showed that those treated with the combination therapy had a higher percentage of survival at one year, of being disease-free at one year and of complete remission, when compared to the CHOP arm alone.
¿ Fred Hutchinson Cancer Research Center, of Seattle, presented research on Mylotarg, an antibody-targeted chemotherapy agent. Research showed patients with acute myeloid leukemia who achieve remission with Mylotarg have prolonged disease-free survival following stem cell transplantation. The data suggest pretransplant therapy with Mylotarg can enable patients to receive curative therapy in the form of hematopoeitic stem cell transplantation. Mylotarg was approved by the FDA in May 2000 and is manufactured by Wyeth-Ayerst Laboratories, of Madison, N.J.
¿ Genitope Corp., of Redwood City, Calif., said a researcher presented positive Phase II results on a patient-specific immunotherapy for the treatment of indolent B-cell non-Hodgkin's lymphoma. The data showed the immunotherapy can stimulate a positive immune response against tumors.
¿ GenStar Therapeutics, of San Diego, presented results of a large animal study of its Maximum Adenovirus Factor VIII vector for the treatment of hemophilia A. The product is a gene delivery system derived from the common cold virus and has been genetically altered to transmit the virus with therapeutic genes responsible for the production of Factor VIII. The study was designed to assess safety and efficacy.
¿ Genta Inc., of Berkeley Heights, N.J., said it showed activity of Bcl-2 antisense against multiple myeloma cells. Its product, Genasense, has received both fast-track and orphan drug designation from the FDA.
¿ Millennium Pharmaceutical Inc., of Cambridge, Mass., presented preclinical and clinical study results on LDP-341, an investigational proteasome inhibitor, saying it is active against multiple myeloma. Millennium said it is committed to initiating additional studies in multiple myeloma in the coming months.
¿ Protein Design Labs Inc., of Fremont, Calif., presented results of two experiments on Smart 1D10 Antibody, currently in a Phase I trial for the treatment of non-Hodgkin's B-cell lymphoma, one examining the intracellular events by which Smart 1D10 induces apoptosis of malignant B cells and the second investigating whether Smart 1D10 would be effective in recruiting a particular type of white blood cell, called the polymorphonuclear granulocyte. An investigator-sponsored Phase II trial of the product and G-CSF is planned. In a separate presentation, its product Nuvion, a humanized antibody for the treatment of steroid-resistant acute graft-vs.-host disease (GvHD), showed no immediate toxicities or other allergic or inflammatory responses. Manifestations of GvHD improved in all 15 of the patients. PDL plans to initiate a Phase II/III trial in that indication next year.
¿ SuperGen Inc., of San Ramon, Calif., said a study of Nipent (pentostatin), its proprietary cancer drug, showed it was well tolerated in 12 steroid-refractory graft-vs.-host disease patients who had failed all other treatments. Five patients achieved a complete response and four a partial response, suggesting Nipent may have activity in this indication. Nipent is FDA-approved for the treatment of hairy cell leukemia.