Genta Inc.'s stock rose more than 50 percent Monday after a busy weekend presenting data from several Genasense studies at the American Society of Hematology (ASH) meeting in San Diego.
Investors seemed thrilled to hear some good news about the product, which was deemed not approvable by an FDA committee in May for melanoma and failed in a Phase III multiple myeloma trial this year. The company even lost Aventis SA as a partner for the product last month on mixed chronic lymphocytic leukemia (CLL) data in which the product met its primary endpoint, but missed secondary endpoints.
However, it was those data, presented in detail at the ASH meeting, that seemed to catch the attention of analysts and investors. On Monday, the stock (NASDAQ:GNTA) rose 48.6 percent, or 67 cents, to close at $2.05.
According to Joy Schmitt, Genta's spokeswoman, the investor response had to do with an "optimism surrounding Genasense" due to the CLL results and positive early clinical data in other indications.
"When it comes to CLL, we have requested a meeting with the FDA to discuss the feasibility of a new drug application submission," Schmitt told BioWorld Today.
Analysts recently have speculated that Genta might need to file for bankruptcy or consider a merger. One analyst told BioWorld Today Monday that positive early clinical data presented at ASH mean little, considering the same early positive data were seen in melanoma and multiple myeloma, in which Genasense failed.
But Brian Rye, an analyst with Janney Montgomery Scott, said the CLL data released in the afternoon were better than expected and might have revived Genasense, perhaps explaining the stock surge.
"It's sort of a combination of coming back from the dead and the Phase III in CLL," Rye said. "The results were a little bit better than what some people had hoped. There's a glimmer of hope now, whereas a couple months ago some people wouldn't have even given them that glimmer of hope."
Rye also said that the CLL results are stronger than the melanoma results, so he believes Genasense might have a chance at getting approved and expects a new drug application filing in the first half of 2005. An FDA committee rejected Genasense in May for melanoma, causing the company to withdraw the NDA. (See BioWorld Today, May 4, 2004, and May 17, 2004.)
Data from the Phase III CLL study showed the addition of Genasense significantly increased the proportion of relapsed or refractory patients who achieved a major response. The trial included 241 patients who were randomized to receive chemotherapy with fludarabine (Flu) and cyclophosphamide (Cy) with or without Genasense. Researchers were looking to see if the addition of Genasense would increase the proportion of patients who achieved complete remission (CR) or nodular partial remission (nPR). Nineteen of the Genasense patients who also received Flu and Cy achieved CR or NPR, compared to eight patients who were treated with chemotherapy alone.
The median duration of response has not been reached for patients in either group, and three of the 19 major responders treated with Genasense have relapsed with progressive disease, compared with two of eight major responders in the other group. Median overall survival for the Flu/Cy group was 26.2 months, whereas it has not yet been reached for patients in the Genasense/Flu/Cy group.
Specific adverse events found in the Genasense group included nausea, fever, fatigue, back pain, weight loss, dehydration and intravenous catheter complications.
The Phase III multiple myeloma study involved 224 patients randomized to receive standard therapy using high-dose dexamethasone with (110 patients) or without (114 patients) Genasense. Patients receiving Genasense had a median time to progression of 3.1 months, compared with 3.5 months for those who received dexamethasone alone. And 16 of the Genasense patients, compared with 20 of the control-group patients, achieved a major clinical response of at least a 75 percent reduction of myeloma protein. There was a significantly higher incidence of nausea, fever, constipation, diarrhea and intravenous catheter complications in the Genasense group. The incidence of Grade III-IV thrombocytopenia was 14 percent in the Genasense group, compared with 5 percent in the dexamethasone group.
Serious adverse events that resulted in the discontinuation of therapy, such as Grade III-IV neutropenia and anemia and renal failure, were equal between the treatment arms. A total of 13 patients in the Genasense group and 10 patients in the dexamethasone group died within 30 days of the last treatment dose.
Other Genasense data presented at ASH showed positive Phase I/II results of Genasense plus thalidomide and high-dose dexamethasone in patients with blood cancers that involve plasma cells, as well as data demonstrating that Genasense has synergistic activity with Millennium Pharmaceuticals Inc.'s Velcade (bortezomib) and Genentech Inc. and Biogen Idec Inc.'s Rituxan (rituximab).
Genta also reported results from two studies using Genasense in combination with other drugs in patients with acute myeloid leukemia (AML). In a Phase II trial with Genasense and Wyeth's Mylotarg (gemtuzumab ozogamicin), the combination showed it could induce complete remission in AML patients that have relapsed.
Aside from Genasense, Genta is studying Ganite as an antitumor drug. Ganite (gallium nitrate injection) is FDA-approved for cancer-related hypercalcemia. Results from an 88-patient Phase II trial showed activity in a variety of patients with various subtypes of advanced non-Hodgkin's lymphoma who had failed to respond to or had relapsed from other treatments.
In other news from the conference:
Amylin Pharmaceuticals Inc., of San Diego, presented new data from its pramlintide (AC137) obesity program and details of a Phase II study initiated with AC2592 for congestive heart failure. In the pramlintide study, obese subjects were able to tolerate higher doses of the drug, up to 240 micrograms three times a day, and they achieved clinically and statistically significant weight loss. Amylin also said its Phase II study of AC2592 will include about 180 subjects, and the primary endpoint will be peak oxygen consumption. Secondary endpoints will include various quality of life and cardiac function measures. Amylin also presented an update on the ongoing open-label extensions of the exenatide pivotal studies showing sustained reductions in blood sugar and body weight through 18 months of treatment.
Bioenvision Inc., of San Diego, showed that clofarabine achieved a threefold greater overall response rate than the current best standard of care in older patients with acute myeloid leukemia who were unsuitable for intensive chemotherapy. In a European study, clofarabine was administered as a monotherapy to 30 AML patients over age 60, and 13 of them achieved a complete response. With four patients achieving a complete response without full platelet recovery, and three others achieving a partial remission, the overall response rate was 66 percent.
Celgene Corp., of Warren, N.J., reported positive Phase II clinical data on Revlimid (lenalidomide) in myelodysplastic syndrome. Transfusion independence was achieved in about 64 percent of patients, and the mean duration of transfusion independence has not yet been achieved. The best response was found in isolated 5q deletion patients. Revlimid, an immunomodulatory drug, has fast-track designation to treat MDS. The company plans to submit a regulatory filing to the FDA in the first quarter.
Cell Therapeutics Inc., of Seattle, said Phase II data of Trisenox (arsenic trioxide) injection in higher-risk and lower-risk myelodysplasia showed that 27 percent of patients experienced a defined hematologic response rate. Of the patients with excess blast cells, 31 percent achieved a response. The trial was conducted at multiple centers in Europe. CTI also presented preliminary results of a Phase II study of a variant of the CHOP chemotherapy regimen that replaces doxorubicin with pixantrone in patients with relapsed aggressive non-Hodgkin's lymphoma. Phase II results of the pixantrone combination regimen, known as CPOP, produced complete responses in 41 percent of patients that had failed the standard CHOP chemotherapy and at least one additional regimen. There was a major objective response rate of 70 percent, with 20 of 43 patients achieving complete responses, 10 experiencing a partial response and six attaining stable disease.
CuraGen Corp., of New Haven, Conn., said Phase I results of CG53135 to prevent oral mucositis in patients receiving high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation suggest the compound is well tolerated following intravenous administration. The results support CuraGen's plan to investigate the compound in Phase II. The company also expects to initiate an additional Phase I trial of CG53135 to treat oral mucositis. CG53135 is a novel fibroblast growth factor that appears to promote both epithelial- and mesenchymal-cell proliferation.
FibroGen Inc., of St. Louis, said Phase I data on FG-2216, its oral anemia therapy, demonstrate the product is safe and well tolerated and stimulates production of erythropoietin and reticulocytes in normal human subjects. Phase IIa results of FG-2216 in chronic kidney disease patients with anemia demonstrated that the oral therapy leads to significant increases in levels of circulating hemoglobin.
Gamida-Cell Ltd., of Jerusalem, said results of its Phase I/II study of StemEx to treat leukemia show the therapy is safe. No serious adverse events were reported. The company expects to investigate the therapy in 2005 in a pivotal Phase III study.
Genmab A/S, of Copenhagen, Denmark, said 55 percent of patients with relapsed or refractory follicular non-Hodgkin's lymphoma treated with HuMax-CD20 achieved a clinical response in a Phase I/II study. The trial had two complete responses and one unconfirmed complete response for a 27 percent complete response rate. The responses were observed in 11 evaluable patients. No dose-limiting toxicity has been reported.
GlycoGenesys Inc., of Boston, said GCS-100LE was shown in vitro to trigger cell death in multiple myeloma, including cell lines resistant to standard treatments. It was found to directly target multiple myeloma cells including their bone marrow microenvironment and including those resistant to traditional cancer agents.
Kosan Biosciences Inc., of Hayward, Calif., said preclinical data of 17-AAG (17-allylamino- 17-demethoxygeldanamycin), or KOS-953, a heat-shock protein-90 inhibitor, showed it had in vitro and in vivo activity against a spectrum of multiple myeloma cells, including those that are sensitive and resistant to cytotoxic chemotherapeutics, the proteasome inhibitor bortezomib, and thalidomide or its derivatives. KOS-953 is in a Phase I single-agent trial and a Phase Ib combination trial with Velcade (bortezomib) in multiple myeloma patients.
Medarex Inc., of Princeton, N.J., presented Phase I and Phase II results of its fully human antibody, MDX-060, in which six patients experienced objective clinical responses out of a total of 56 patients with refractory or relapsed CD30-positive lymphomas. Overall, 43 percent of the patients experienced disease remission or stabilization.
MGI Pharma Inc., of Minneapolis, and SuperGen Inc., of Dublin, Calif., said Dacogen for injection in patients with myelodysplastic syndrome showed an overall response rate of 17 percent with a median response duration of 266 days, compared to zero percent in the supportive-care arm. For all patients in the Dacogen arm, median time to progression or death was 340 days vs. 219 days for supportive-care patients. The primary toxicity associated with Dacogen was myelosuppression. Preliminary results of a Phase II study of Dacogen in 35 Gleevec-refractory or -intolerant patients with chronic myelogenous leukemia showed an overall hematologic response rate of 65 percent. SuperGen also presented data showing its cancer drug Nipent (pentostatin for injection) had activity with modest toxicity in combination with other chemotherapy agents in treating chemotherapy-na ve B-cell chronic lymphocytic leukemia and hairy-cell leukemia. In addition, the agent showed particular activity in treating children and adolescents with chronic graft-vs.-host disease, and in high-risk patients undergoing reduced-intensity transplantation regimens.
NeoRx Corp., of Seattle, said Phase I/II trials of STR, its bone-targeted radiotherapy, showed a four-year survival rate of 70 percent and a complete response rate of 40 percent in multiple myeloma patients at different clinical stages. The 10 patients received various doses of STR and melphalan prior to transplantation. Two of three patients dosed six years ago remain alive. The estimated median survival for 83 patients treated with STR in two Phase I/II studies was 5.4 years. NeoRx is conducting a Phase III trial of STR in primary refractory multiple myeloma patients.
Novartis Oncology, of East Hanover, N.J., a unit of Novartis AG, said new data on Gleevec (imatinib mesylate), a therapy approved for chronic myelogenous leukemia, demonstrated that newly diagnosed patients with a certain form of leukemia receiving 400 mg daily maintained their response to therapy long term. A separate study found that patients receiving 800 mg daily had better outcomes than patients receiving 400 mg daily. Other results presented at ASH showed that a new drug, BMS-354825, can treat patients who have become resistant to Gleevec. Phase I data demonstrated that 86 percent of the patients treated with the new drug achieved a complete hematologic response.
Nuvelo Inc., of Sunnyvale, Calif., said data from a Phase II trial showed that alfimeprase has the potential to restore function in patients with occluded central venous access devices. The data also showed that alfimeprase is a well-tolerated therapy for use in catheter occlusion. The company plans to initiate a Phase III development program.
Ortho Biotech Products LP, a subsidiary of J&J, of New Brunswick, N.J., said interim results showed a statistically significant difference in hemoglobin response rates of epoetin alfa (Procrit) and darbepoetin alfa in treating chemotherapy-related anemia. Hemoglobin levels increased more than 1 g/dL from baseline within the first four weeks of treatment for 47 percent of patients treated with epoetin alfa, compared to 33 percent of patients treated with darbepoetin alfa.
Point Therapeutics Inc., of Boston, presented Phase I data of PT-100 (talabostat) and rituximab in patients with indolent non-Hodgkin's lymphoma and talabostat in healthy subjects. In the NHL study, 20 patients received talabostat for six days following each rituximab treatment at three dose levels. Researchers observed two partial tumor responses, one at the 400(mu)g-dose level and one at the 800(mu)g-dose level, and 13 patients had stable disease at day 28 of treatment. The most frequent adverse event across all doses was edema. Talabostat was well tolerated and researchers observed significant dose-related increases in granulocyte-colony stimulating factor and IL-6.
Seattle Genetics Inc., of Bothell, Wash., said ongoing Phase II studies of SGN-30 in anaplastic large-cell lymphoma and Hodgkin's disease demonstrate that it is well tolerated and has antitumor activity. Preliminary data in a Phase I trial of SGN-40 in multiple myeloma indicate that the product is well tolerated at low doses. Preclinical studies of both products suggest synergies with conventional chemotherapy regimens.
Telik Inc., of Palo Alto, Calif., said a Phase II trial of Telintra (TLK199) in myelodysplastic syndrome showed that 61.5 percent of patients had clinically significant improvement in one or more blood cell lineages. Clinical responses were associated with decreased red blood cell, platelet and growth factor support requirements, in some cases leading to transfusion independence. Telintra was well tolerated in the patient population, which had a median age of 74 years.
Xcyte Therapies Inc., of Seattle, said results from two trials of Xcellerated T cells in patients with multiple myeloma showed that recovery of lymphocytes and T cells was much more rapid than what has been seen in patients treated with the same regimen without Xcellerated T cells. Thirty-one of 35 patients had a significant tumor response, and 21 percent had a 90 percent or greater decrease in the serum M protein. Progression-free survival was 67 percent at one year and 58 percent at two years. Xcyte also said Phase I/II data showed that 12 of 17 chronic lymphocytic leukemia patients receiving Xcellerated T cells had a 50 percent or greater decrease in the size of enlarged lymph nodes.
Ziopharm Inc., of New Haven, Conn., said preclinical data was presented on ZIO-102, the company's second organic arsenic product. ZIO-102 was shown to be significantly more active against several human leukemia cell lines compared to arsenic trioxide. Ziopharm's product also was less toxic in both in vivo and in vitro assays. The company plans to move the product into Phase I trials next April.