Below is a summary of updates to the BioMedReports.com database of over 200 entries included in the FDA and Clinical Trial Calendars. The FDA Calendar includes companies with pending new drug, biological agent, or medical device new product decisions at the FDA sorted by their PDUFA decision deadline dates while the Clinical Trial Calendar encompasses pending clinical trial results (with a focus on late-stage, Phase 3 trials), pending new submissions to the FDA (e.g. NDA, BLA, 510k, PMA, sNDA, sBLA filings), and pending re-submissions to the FDA for complete response rulings by the agency which require more information before an approval can be granted.
Allos Therapeutics (NASDAQ:ALTH): On 5/30/09 , ALTH updated data from the Company’s pivotal Phase 2 PROPEL study of pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). The overall response rate for pralatrexate as evaluated by central independent oncology review using International Workshop Criteria (IWC) was 28% (30 of 109 evaluable patients) with a median duration of response of 9.4 months, or 287 days. Of the 30 patients who responded to pralatraxate, 21 patients (70%) did so after cycle one of therapy. Median overall survival was 14.7 months, with 57% of responders surviving 12 months or more. The most common Grade 3/4 adverse events were thrombocytopenia, mucositis, neutropenia, and anemia.
ALTH filed a NDA for pralatrexate in late March for the treatment of patients with relapsed/refractory peripheral T-cell lymphoma (PTCL). ALTH received a priority (six-month) review designation on 5/26/09 with a PDUFA decision date of 9/24/09 . PTCL comprises a biologically diverse group of hematologic malignancies that typically has a worse prognosis than other types of lymphoma and is less responsive to traditional chemotherapy regimens. There are currently no agents approved by the FDA for the treatment of patients with PTCL.
Biovest (OTC:BVTI): On 5/31/09, BVTI announced that an eight year pivotal, randomized, multi-center, double-blind, controlled Phase 3 clinical study has shown that BiovaxID (personalized therapeutic anti-cancer vaccine) significantly prolonged disease-free survival in follicular non-Hodgkin’s lymphoma. The study found that patients who received BiovaxID experienced a median disease-free survival of 44.2 months compared to 30.6 months for those who received a control vaccine – an increase of 47%. In the study, with a median follow-up of 4.7 years, patients receiving BiovaxID experienced a 38% lower risk of disease recurrence compared to patients receiving the control vaccine.
In addressing regulatory and commercial plans for BiovaxID, Biovest’s President and General Counsel, Samuel Duffey, commented, “We have already initiated discussions with the FDA and EMEA and are preparing for further meetings with those agencies and other international regulatory authorities in order to share our significant results and determine the most appropriate approval regulatory pathways. In addition, we plan to make BiovaxID available throughout most of Europe on a named-patient basis. This compassionate-use drug access program allows European physicians to prescribe drugs to qualifying patients before approvals are granted, assuming the protocols for each participating country are followed.”
On 5/29/09, Celldex (NASDAQ:CLDX) announced its proposed acquisition (expected to close during 3Q09) of CuraGen (NASDAQ:CRGN), which adds to Celldex’s clinical development program a number of important milestones anticipated over the next 12-18 months including: (1) Phase 2 CDX-110 ACT II and ACTIVATE data in GBM, (2) Phase 2 CR011 breast cancer and melanoma data, (3) Phase 1 CDX-1307 combination data in epithelial cancers, (4) Phase 2 ACT III study of CDX-110 in GBM; design of randomized study in GBM, (5) Phase 2 CR011 studies in breast cancer and melanoma; determine next steps for CR011 development in breast cancer and melanoma, (6) Phase 1 CDX-1307 novel combination, (7) Phase 2 CDX-1307 randomized study in bladder cancer (8) Phase 1/2 CDX-1401 study in multiple solid tumors.
CuraGen is developing CR011-vcMMAE as an antibody-drug conjugate that is currently being evaluated in two Phase 2 trials assessing the safety and efficacy in the treatment of melanoma and for the treatment of metastatic breast cancer, and in a Phase I trial to evaluate the safety and activity of alternate dosing schedules. CRGN is scheduled to make two presentations at ASCO on 6/1/09 for CR011-vcMMAE, including Phase 1 melanoma pharmacokinetic data and Phase 1/2 data for locally advanced or metastatic breast cancer.
At ASCO, CLDX and Pfizer (NYSE:PFE) announced the presentation of updated data from two clinical trials of CDX-110 in newly-diagnosed glioblastoma multiforme (GBM is a type of brain cancer). CDX-110 is an investigational immunotherapeutic, anti-cancer vaccine that targets the tumor-specific molecule called epidermal growth factor receptor variant III (EGFRvIII). The compound was developed by CLDX and is now partnered with Pfizer.
The companies stated in a press release that data from the 40 evaluable patients in ACTIVATE and ACT II trials continue to suggest that vaccination with CDX-110 may be able to improve time to tumor recurrence and overall survival when used in patients with newly-diagnosed GBM. These data also continue to suggest that tolerability and side effects associated with CDX-110 are minimal.
ACTIVATE Results: In this single arm Phase 2 study, 18 patients with newly diagnosed and optimally resected EGFRvIII-positive GBM received CDX-110 as a monotherapy following completion of chemoradiation with concurrent temozolomide. Median overall survival (OS) was 26 months and median time to progression ((NYSE:TTP)) was 14.2 months. Additionally, three patients remain without relapse more than 4 years from surgery and continue to receive the vaccine within the clinical trial.
ACT II Results: In this single arm Phase 2 study, 22 patients with newly diagnosed and optimally resected EGFRvIII-positive GBM received CDX-110 in combination with maintenance temozolomide after having completed chemoradiation with concurrent temozolomide. Median time to progression (TTP) is 15.2 months and three patients continue without relapse after more than two years. Results to date from this ongoing study estimate median overall survival to be 23.6 months (data are not yet final). In addition, and in line with preclinical data that suggested the combination with temozolomide could augment immune responses, patients show robust serological evidence of an immune response against EGFRvIII.
Efficacy data from both ACTIVATE and ACT II compare favorably to data for a historical control group of 17 patients, matched for EGFRvIII expression, extent of resection and performance status (Median TTP: 6.3 months; Median OS: 15.0 months). In both studies, CDX-110 was generally well tolerated with local injection site reactions being the most commonly reported toxicity.
ImmunoGen (NASDAQ:IMGN): On 5/30/09, IMGN announced the presentation of trastuzumab-DM1 (T-DM1) clinical data. T-DM1, an antibody-drug conjugate, consists of ImmunoGen’s DM1 cancer-cell killing agent linked to the HER2-targeted antibody, trastuzumab, developed by Genentech, Inc. (a wholly-owned member of the Roche Group) (OTCQX:RHHBY).
Among the findings presented were: (1) 25% of patients had a confirmed objective response as assessed by an independent review facility (IRF), the primary endpoint of the study. Among these 28 patients, 22 were still receiving T-DM1 at the time of data cut-off for presentation; (2) 35% of patients had clinical benefit by IRF that consisted of either a confirmed objective response or stable disease lasting for at least 6 months; and (3) the anti-tumor activity seen in patients who had received lapatinib as well as trastuzumab was similar to that seen in the overall study population.
The most common severe (Grade 3 or 4) adverse events were hypokalemia (lowered potassium levels) in 8 percent of patients and thrombocytopenia (lowered platelet levels) in 7 percent of patients. No severe (Grade 3 or 4) cardiac-specific toxicity was observed. Genentech recently completed patient enrollment in a Phase 2 study evaluating T-DM1 for third-line treatment of advanced HER2-positive breast cancer. Genentech has stated that, if the data from this study are compelling, it will discuss an earlier approval path with the FDA. Data is expected in late 2009 or early 2010.
Immunomedics (Nasdaq:IMMU): On 5/31/09, IMMU reported a 30% objective response rate in 10 evaluable patients with inoperable, advanced pancreatic cancer treated with a novel targeted radiation therapy developed by the Company in combination with gemcitabine. The interim results from the ongoing Phase 1b dose-escalation study were presented at ASCO.
Eleven treatment-naive patients, of which all but 1 had stage 4 or metastatic pancreatic cancer, were enrolled in this dose exploration study to receive 1 of 3 fractionated yttrium-90 (Y-90) doses: 6.5, 9.0 and 12.0 mCi/m(2), given once a week for 3 weeks in combination with low doses of gemcitabine as a radiosensitizing agent. Two of 3 patients at the 12.0 mCi/m(2) dose level had more than 30% tumor shrinkage to qualify as partial responders by RECIST criteria. The third patient is too early for evaluation, but is showing evidence of tumor shrinkage. One patient receiving 6.5 mCi/m(2) of Y-90 also was a partial response. Overall, half of the evaluable patients showed evidence of tumor shrinkage or stabilization after this therapy.
In addition, 2 patients survived for more than 1 year from the start of treatment, despite the dismal life expectancy of 4 to 6 months from diagnosis for most patients with advanced pancreatic cancer, due to lack of early detection and effective treatment. One had received 4 cycles of this therapy, and the other received three. The targeted radiation therapy penetrates and kills cancer cells by using the Company's patented humanized monoclonal antibody called clivatuzumab, or hPAM4, to deliver beta-radiation beams produced by the radioisotope, yttrium-90, directly to the tumor. Clivatuzumab binds to 85% of pancreatic cancers, but does not target cells in normal pancreas or pancreatitis.
On 5/30/09, IMMU announced that milatuzumab, the Company's proprietary humanized anti-CD74 antibody, produced disease stabilization in some patients with multiple myeloma and is well tolerated at doses up to 16.0 mg/kg. CD74 is a transmembrane protein that is highly expressed in multiple myeloma and other B-cell lymphomas.
At the time of reporting, 24 patients had received milatuzumab, twice weekly, at 1 of 4 dose levels: 1.5, 4.0, 8.0 or 16.0 mg/kg, for 4 weeks. Milatuzumab was rapidly cleared at these dose levels with little accumulation in the blood. In spite of rapid clearance, 4 patients had encouraging disease stabilization for at least 12 weeks post-treatment, one continuing for more than 8 months. These patients (3 at 4.0 mg/kg dose level and 1 receiving 8.0 mg/kg milatuzumab) appeared to have higher serum levels of the anti-CD74 antibody. There have been no objective responses in 21 evaluable patients.
OncoGenex Pharma (NASDAQ:OGXI): On 5/30/09, OGXI, announced the final results of a Randomized Phase 2 Trial which indicated a survival benefit in patients treated with OGX-011 in combination with docetaxel compared to docetaxel alone (the current standard care for patients with advanced prostate cancer). The median overall survival in patients with advanced metastatic prostate cancer who were treated with OGX-011 plus docetaxel in a randomized Phase 2 trial was 23.8 months compared to 16.9 months for patients treated with docetaxel alone -- a 6.9 month observed survival advantage for the OGX-011 arm.
The unadjusted hazard ratio (HR), a measure used to compare the death rates between treatment groups, was 0.61, representing a 39% lower rate of death for patients treated with OGX-011.Study investigators concluded that OGX-011 treatment was well tolerated in combination with docetaxel. According to OGXI, the reported data for OGX-011 clearly justify advancing the compound into Phase 3 clinical development, and the Company expects the data will be crucial to their partnering discussions for future clinical development and potential commercialization.
Roche (OTCQX:RHHBY): Median overall survival was 13.8 months in the Herceptin (trastuzumab) plus chemotherapy group compared with 11.1 months in the standard chemotherapy group in a Phase 3 trial of patients with stomach cancer. Research by Genentech has shown that the HER-2 receptor is also found in about 25% of patients with stomach cancer, providing an opportunity to extend survival in this targeted population group.
The median progression-free survival was 4.8 months for the combination therapy of Tarceva (erlotinib) and Avastin (bevacizumab) versus 3.7 months for the placebo group in a 768-patient Atlas study of patients with advanced cases of lung cancer. Tarceva is co-marketed by OSI Pharma (NASDAQ:OSIP) and Roche.
On 5/30/09, AstraZeneca (NYSE:AZN) announced that Zactima (vandetanib) (an oral anti-cancer drug) demonstrated median progression-free survival in combination with docetaxel of 17.3 weeks compared to 14 weeks for patients on chemotherapy alone in a pivotal trial (Zodiac) that involved 1,391 patients with advanced non-small cell lung cancer whose disease has worsened after chemotherapy. AZN plans to file for U.S. marketing approval with the FDA by 6/30/09.
Disclosure: No positions.