Multiple Myeloma

January 25, 2016

Sellas Life Sciences Group reported positive results from a phase I/II clinical study of the WT1 cancer vaccine in patients with multiple myeloma (MM) following autologous stem cell transplantation. Sellas’s trial enrolled 15 patients, each patient receiving chemotherapy and stem cell transplantation and followed by one to two cycles (six vaccines per cycle) of the company’s WT1 cancer vaccine. Of the patients enrolled, 60% were found to have high risk cytogenetics at diagnosis (9/15), including del p53; this is the most difficult population to maintain in long-lasting remission. Initial data have shown positive safety findings and that treatment with the WT1 vaccine was well-tolerated. Initial results from the study have demonstrated positive immune response data and safety findings as well as early efficacy data. Three patients with high-risk cytogenetics achieved an immune response against WT1 peptides encoded in the vaccine, and two of these patients continued in remission at the time of last follow-up at one year; the third patient was in remission as of the first, three-month follow-up and will continue to be followed through one year. Sellas intends to assess the efficacy of the WT1 cancer vaccine in MM in a larger phase II/III trial including patients with standard risk disease following induction chemotherapy in 2016.

December 21, 2015

Janssen-Cilag International has released results of a phase I/II study of daratumumab, in combination with lenalidomide and dexamethasone, for treatment of relapsed or refractory multiple myeloma. The cohort expansion phase of the open label, international, multicenter, dose escalating GEN503 study enrolled 32 patients who had received a median of two prior lines of therapy. The two-part GEN503 study is comprised of a dose escalation study (part one) and a cohort expansion study (part two). In part one, patients received daratumumab in combination with lenalidomide (25mg orally on days one through 21 of every 28-day cycle) and dexamethasone (40mg intravenously and orally once weekly). Daratumumab 2-16mg/kg body weight was administered as an intravenous infusion given weekly for the first eight weeks, then biweekly for the next 16 weeks, and then monthly until disease progression or unmanageable toxicity for 24 months in total. In part two, all patients were administered the recommended phase II daratumumab dose (16mg/kg), patients refractory to lenalidomide were excluded, and patients with at least one prior line of therapy were included. Stringent complete response (sCR) was reported in 25% of patients (n=8), complete response (CR) was reported in 9% (n=3), very good partial response (VGPR) was reported in 28% (n=9), and partial response (PR) was reported in 19% (n=6). Among all patients, the median times to first and best response were one month (95% confidence interval [CI], 0.5-5.6) and 5.1 months (95% CI, 0.5-14.4), respectively. The median duration of response was not reached.

December 14, 2015

Takeda Pharmaceutical has reported results of a phase III trial of NINLARO (ixazomib) for relapsed and/or refractory multiple myeloma. The TOURMALINE-MM1 trial is an international, randomized, double-blind, placebo-controlled trial designed to evaluate once-weekly oral ixazomib plus lenalidomide and dexamethasone compared to placebo plus lenalidomide and dexamethasone. Trial results demonstrate a statistically significant (35%) improvement in progression free survival (PFS), with patients treated in the ixazomib arm living for a significantly longer time without their disease worsening compared to patients in the control arm (20.6 months vs. 14.7 months in control group; Hazard Ratio [HR] 0.742; p = 0.012). Overall response rate (ORR) was 78.3% in the ixazomib arm and median duration of response was 20.5 months, v. 71.5% and 15 months in the control group. Median PFS in high-risk patients (HR 0.543; HR 0.596 in patients with del(17p)) was similar to that in the overall patient population and in standard-risk patients. The most common grade three adverse events included neutropenia, anemia, thrombocytopenia and pneumonia. Gastrointestinal events included diarrhea, nausea, and vomiting. Peripheral neuropathy rates were 28% in the IRd arm v. 21% in the control arm, 35% v. 21% had rash events, 8% v. 10% had acute renal failure, and 4% v. 3% had heart failure. NINLARO was recently approved by the FDA in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.

September 8, 2015

Janssen R&D has released results from a multicenter, two-part, open-label, phase I/II study of daratumumab for relapsed or refractory multiple myeloma. In part 1, 32 patients were treated with escalating doses and no maximum tolerated dose was identified. In part 2, 72 patients were enrolled in a dose expansion cohort and received either 8mg/kg (30 patients) or 16mg/kg (42 patients) of daratumumab at various schedules until disease progression or unmanageable toxicity to optimize doses identified in part 1. Following that study, 16 mg/kg was chosen as the dose to be used in all daratumumab clinical trials. Patients had a median of four prior lines of therapy and 79% were refractory to their last therapy, including both lenalidomide and bortezomib (64%). Additionally, 76% of patients previously received an autologous stem cell transplant. In the 16mg/kg cohort, the ORR was 36% (11 partial responses, two very good partial responses and two complete responses) and 10% in the 8mg/kg cohort (three partial responses). The two complete responses were confirmed with the use of a novel assay. Median progression-free survival was 5.6 months (95% CI: 4.2, 8.1) and 65% (95% CI: 28, 86) of responders remained in remission at 12 months. In the 16mg/kg cohort, serious adverse events (AEs) occurred in 33% of patients. Infusion-related reactions (IRRs) occurred in 71% of patients in both the 8mg/kg and 16mg/kg cohorts, and all were grades 1 and 2, except for the occurrence of grade 3 reactions in one patient. The majority of IRRs occurred during the first infusion, with notably fewer during subsequent infusions. No patient discontinued treatment due to an IRR. The most common AEs in either treatment group were fatigue, allergic rhinitis and pyrexia (fever). On July 9, Janssen completed the rolling submission of its BLA for daratumumab to the FDA for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an IMiD, or who are double refractory to a proteasome inhibitor and an immunomodulatory agent. Daratumumab received Breakthrough Therapy designation from the FDA for this patient population in May 2013.

June 15, 2015

Bristol-Myers Squibb and AbbVie released results of a randomized, open-label, phase III study of elotuzumab in combination with lenalidomide and dexamethasone (ELd) v. lenalidomide and dexamethasone alone (Ld) for the treatment of relapsed or refractory multiple myeloma. The ELd arm demonstrated a 30% reduction in the risk of disease progression or death compared to the Ld arm (HR 0.70, 95% CI, [0.57, 0.85]; p=0.0004). The PFS rates in the ELd arm v. the Ld arm were 68% v. 57% at one year and 41% v. 27% at two years, respectively. A significant overall response rate also was observed with 79% (74% to 83%) in the ELd arm compared to 66% (60% to 71%) in the Ld arm (odds ratio, 1.9; 1.4 to 2.8; p=0.0002). The safety profile was consistent with previously-reported studies and there were minimal incremental adverse events with the addition of elotuzumab to lenalidomide and dexamethasone.

March 16, 2015

Amgen and its subsidiary Onyx Pharmaceuticals reported results of a phase III head-to-head clinical trial evaluating Kyprolis (carfilzomib) for injection in combination with low-dose dexamethasone v. Velcade (bortezomib) and low-dose dexamethasone for treatment of multiple myeloma. The study enrolled 929 patients whose multiple myeloma has relapsed after at least one, but not more than three prior therapeutic regimens. Patients received Kyprolis as a 30-minute infusion along with low-dose dexamethasone (20mg). For cycle one only, Kyprolis was administered at 20mg/ m2 on days one and two, followed by escalation to 56mg/m2 on days eight, nine, 15 and 16. Patients who tolerated 56mg/m2 in cycle one were kept at this dose for subsequent cycles on days 1, 2, 8, 9, 15 and 16 on a 28-day cycle. Patients who received Velcade (1.3mg/ m2) with low-dose dexamethasone (20mg) were administered Velcade subcutaneously or intravenously at the discretion of the investigator and in accordance with regulatory approval of Velcade. Patients with relapsed multiple myeloma treated with Kyprolis lived twice as long without their disease worsening, demonstrating statistically and clinically significant superiority over Velcade (median PFS 18.7 months v. 9.4 months, HR=0.53, 95% CI, 0.44 0.65). Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms.

December 15, 2014

Celgene released results of a phase IIIb study of pomalidomide plus low-dose dexamethasone in patients with relapsed and refractory multiple myeloma. The single-arm study enrolled 599 patients with refractory, or relapsed and refractory, disease who had previously failed lenalidomide and bortezomib. At a median follow-up of 6.8 months with a median four cycles received, the median PFS and OS were 4.2 months and 11.9 months, respectively. The ORR was 35%, with 8% of patients achieving at least a very good partial response (VGPR). In patients refractory to prior lenalidomide (n=572) or lenalidomide and bortezomib (n=473), similar PFS (4.2 months and 4.1 months), OS (12 months for each) and ORR (34% and 35%) were achieved. A subgroup analysis was conducted to determine the impact of the therapy on patients with moderate renal impairment (RI). Of those enrolled, 215 had moderate RI (Creatinine clearance greater than 45 mL/min but less than 60 mL/min). ORR was generally similar between patient groups receiving pomalidomide plus low-dose dexamethasone (37% with moderate renal impairment v. 33% without moderate renal impairment) despite differences in renal function. Pomalidomide dosing was 4mg daily for days one to 21 of a 28-day cycle. Dexamethasone was given at 40mg/day (20mg for > 75 years) on days 1, 8, 15 and 22. Dose intensity was comparable in both groups (94% and 93%). No dose adjustment was required for renal impairment. Pomalidomide is marketed as Pomalyst in the U.S. and Imnovid in the E.U.

August 11, 2014

Amgen and Onyx Pharmaceuticals reported results of a phase III study of Kyprolis (carfilzomib) for injection in combination with Revlimid (lenalidomide) and low-dose dexamethasone (KRd) for multiple myeloma. Patients were randomized to receive Kyprolis (20mg/m on days one and two of cycle one only, then 27mg/m subsequently), in addition to a standard dosing schedule of lenalidomide (25mg per day for 21 days on, seven days off) and low-dose dexamethasone (40mg per week in four week cycles), versus lenalidomide and low-dose dexamethasone alone. The study randomized 792 patients at sites in North America, Europe and Israel. Patients treated with Kyprolis for injection in combination with Revlimid and low-dose dexamethasone lived significantly longer without their disease worsening (median 26.3 months) compared to patients treated with Revlimid and low-dose dexamethasone (Rd) (median 17.6 months) (HR=0.690, 95% CI, 0.570, 0.834, p<0.0001). Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms. These results will form the basis for regulatory submissions throughout the world beginning in the first half of 2015.

June 9, 2014

Novartis released results of a phase III trial of LBH589 (panobinostat) in combination with bortezomib and dexamethasone compared to treatment with the same regimen with placebo in patients with relapsed or relapsed and refractory multiple myeloma. The randomized, double-blind, placebo-controlled, multicenter global registration trial enrolled 768 patients in 215 trial sites worldwide. In the LBH589 arm, there was a four-month prolongation of median PFS (12 months v. eight months in the placebo arm). The effect of LBH589 was observed across all patient subgroups (for example by age or prior exposure to bortezomib or immunomodulatory therapy). The findings also showed adding LBH589, a pan-deacetylase (pan-DAC) inhibitor, to bortezomib and dexamethasone led to a significant increase in higher quality responses compared to standard-of-care therapy alone, as evidenced by a nearly two-fold increase in complete/near complete response rates (28% v. 16%, respectively; p=0.00006). The most common grade 3/4 adverse events in the LBH589 combination arm were thrombocytopenia (67% v. 31% with placebo), lymphopenia (53% v. 40% with placebo), neutropenia (35% v. 11% with placebo) and diarrhea (26% v. 8% with placebo). Adverse events were generally manageable through supportive care and dose reductions. LBH589 was granted Priority Review by the FDA and additional global regulatory submissions are underway.

January 7, 2013

Bristol-Myers Squibb reported results from a phase II trial of elotuzumab in combination with lenalidomide and low-dose dexamethasone for the treatment of multiple myeloma. This randomized, multi-center, open-label study enrolled patients with previously treated multiple myeloma. Subjects received either 10mg/kg or 20mg/kg of elotuzumab intravenously on days 1, 8, 15 and 22 of a 28-day cycle in the first two cycles, and then on days 1 and 15 of subsequent cycles. Subjects also received lenalidomide 25mg PO daily on days 1 to 21 and dexamethasone 40mg PO weekly. Results demonstrated in the 10mg/kg arm, median progression-free survival (PFS) was not reached after 20.8 months of follow up (n=36) and the objective response rate (ORR; according to the International Myeloma Working Group response criteria) was 92%. Of patients who received elotuzumab at a dose of 20mg/kg, median PFS was 18.6 months (n=37) and ORR was 76%. Elotuzumab was well tolerated. The most frequent adverse events were lymphopenia, neutropenia, thrombocytopenia, anemia, leukopenia, hyperglycemia, pneumonia, diarrhea, fatigue and hypokalemia. BMS also is studying elotuzumab in two phase III trials for treatment of relapsed/refractory multiple myeloma.

December 17, 2012

Senesco Technologies released interim results from an ongoing phase Ib/IIa trial of SNS01-T for the treatment of multiple myeloma, mantle cell (MCL) and B-cell lymphoma (DLBCL). This open-label, multiple-dose, dose-escalation study enrolled two patients so far with relapsed or refractory multiple myeloma. Subjects received SNS01-T or 0.0125mg/kg per dose intravenously, while the next three arms will receive SNS01-T or 0.05mg/kg, 0.2mg/kg or 0.375mg/kg per dose intravenously. Blood levels of monoclonal (M)-protein were measured using serum protein electrophoresis. Data showed patients 41-002 and 42-002 in cohort 1, serum levels of M-protein remained within 25% of the baseline values (3.60g/dL, 3.0g/dL respectively) at weeks three (3.90g/dL, 2.8g/dL) and six (4.20g/dL, 2.8g/dL), stable disease. For patient 42-002, M-protein stayed within 25% of baseline at week 10 (3.2g/dL)—four weeks after the end of treatment. M-protein levels for patient 43-001 increased from baseline to week three by 26% and from baseline to week six by 30%. Indicative of the partial disappearance of cancer cells, the plasma cell levels for patients 41-002 and 42-002 declined from 70% to 50% and from 50% to 15%, respectively. Plasma cell levels for patient 43-001 increased from 70% at baseline to 97% at end of treatment. Based on these data, Senesco Technologies will continue to dose patients in the other three arms.

October 29, 2012

Celgene International reported results from a phase III trial of pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone for multiple myeloma. This multi-center, randomized, open-label study enrolled patients with relapsed and/or refractory multiple myeloma. Subjects in Arm 1 received 4mg pomalidomide on days 1-21 of each 28-day cycle, with patients 75 years or younger also receiving 40mg of low-dose dexamethasone and patients older than 75 receiving 20mg of low-dose dexamethasone on days 1, 8, 15 and 22 of each 28-day cycle, until disease progression. Subjects in Arm 2 received 40mg high-dose dexamethasone on days 1-4, 9-12 and 17-20 of each 28-day cycle if they were 75 years or younger, and patients older than 75 received 20mg high-dose dexamethasone on days 1-4, 9-12 and 17-20 of a 28-day cycle, until disease progression. The study met its primary endpoint of improvement in progression-free survival (PFS) at the PFS final analysis. Additionally, the study crossed the superiority boundary for overall survival (OS), a key secondary endpoint. As a result, patients who had not yet progressed in the high-dose dexamethasone arm should be crossed-over to the pomalidomide plus low-dose dexamethasone arm. Celgene has submitted an NDA application to the FDA, as well as an MAA application to the EMA.

August 20, 2012

Senesco Technologies issued results from a phase Ib/IIa trial of SNS01-T for the treatment of multiple myeloma. This open-label, multiple-dose, dose-escalation study enrolled six patients with relapsed or refractory multiple myeloma. Subjects received SNS01-T 0.0125mg/kg (approximately 1mg/patient) by intravenous infusion twice-weekly for six weeks. The drug was well tolerated and deemed safe to increase the dosage. Senesco will be adding three more arms to the study, with doses of 0.05mg/kg, 0.2mg/kg and 0.375mg/kg, increasing the number of subjects to 15.

December 26, 2011

Millennium reported interim results from a phase I/II trial oral MLN-9708 for multiple myeloma. This open-label dose escalation study planned to enroll 58 subjects with newly diagnosed multiple myeloma who had not previously received systemic treatment. The subjects received MLN-9708 plus lenalidomide and low-dose dexamethasone. Data are from 15 evaluable subjects. Of the 15 evaluable subjects, 100% achieved a partial response or better, including four complete responses, five very good partial responses and six partial responses. Fourteen of 15 achieved partial response or better after cycle one and 100% achieved partial response or better by cycle two. The maximum tolerated dose was of MLN-9708 was determined to be 2.97 mg/m2 weekly dosing; the recommended weekly phase II dose was established at 2.23 mg/m2. The most common adverse events were fatigue and rash (60%).

August 2, 2010

Onyx reported positive results from a phase IIb trial of carfilzomib for the treatment of multiple myeloma. This open-label, single-arm trial, 003-A1, enrolled 266 heavily-pretreated subjects with relapsed and refractory disease. All subjects had received a median of five prior therapeutic regimens. Carfilzomib was administered at 20mg/m2 for the first cycle followed by 27mg/m2 thereafter for up to 12 cycles. Responses and progression were determined according to the International Myeloma Working Group criteria. Carfilzomib resulted in an overall response rate (partial response or greater) of 24% and a median duration of response of 7.4 months. The clinical benefit rate (minimal response or greater) in the study population was 36%. Carfilzomib was well-tolerated and there were no new or unexpected toxicities observed.

March 24, 2008

Millennium reported positive updated results from a phase I/II trial of Velcade plus melphalan and prednisone (VcMP) for the first-line treatment of newly diagnosed multiple myeloma. The study enrolled sixty subjects who were ineligible for stem cell transplantation. The subjects received Velcade at 1.3 mg/m2 or 1.0 mg/m2 twice weekly in weeks one, two, four and five for four six-week cycles (eight doses per cycle), followed by once weekly in weeks one, two, three and four for five, five-week cycles (four doses per cycle) in combination with melphalan at 9 mg/m2 and prednisone at 60 mg/m2 once daily on days one through four of each cycle. Treatment continued for a maximum of forty nine weeks with a median number of thirty nine weeks. Results showed an immunofixation-negative complete remission rate of 32% and an overall response rate of 89% with VcMP. The overall survival rate at thirty eight months was 85% with VcMP compared to the 38% historical control with melphalan and prednisone (MP) (p<0.0001). The median overall survival for VcMP has not been reached, compared to twenty six months among the historical control with MP. The median time-to-disease progression with VcMP was 27.2 months compared to twenty months for the historical control with MP (p=0.001). The median event-free survival with VcMP was twenty five months compared to fifteen months for the historical control with MP (p=0.001). A sNDA is currently under Priority Review by the FDA for this indication.

August 6, 2007

Genzyme reported positive results from a phase III trial of Mozobil for the treatment of multiple myeloma. This randomized, double-blind, placebo-controlled trial enrolled 302 subjects who were undergoing a hematopoietic stem cell transplant (HSCT) for multiple myeloma. Subjects were treated with Mozobil following granulocyte-colony stimulating factor (G- CSF) or placebo following G-CSF. In the primary efficacy endpoint, 72% of subjects treated with Mozobil and G-CSF achieved the target threshold for collection of at least 6 million CD34+cells/kg from the peripheral blood with two days or fewer of apheresis sessions, compared with 34% of subjects in the G-CSF/placebo group (p<0.0001). Secondary endpoint were achieved as well; the median number of days to achieve the target of 6 million cells was one day for the Mozobil/G-CSF group and four days for the G-CSF/placebo group. Genzyme plans to file for US and European regulatory approval in the first half of 2008.

Oncogenics and Isis released positive preliminary results from a phase II trial of OGX-011 for the treatment of metastatic hormone refractory prostate cancer. This trial enrolled 42 subjects who were randomized to receive 640 mg/week OGX-011 plus prednisone plus either mitoxantrone or docetaxel. The results are from a median follow-up of 7.4 months. In the cohort receiving OGX-011 plus docetaxel: death occurred in 10% of the population, 30% experienced disease progression, 35% had a 50 percent decrease in prostate specific antigen (PSA), and 55% had a 30 percent decrease in PSA. In the cohort receiving OGX-011 plus mitoxantrone: death occurred in 32% of the population, 59% experienced disease progression, 23% had a 50 percent decrease in PSA and 32% had a 30 percent decrease in PSA. Treatment in both arms was generally well tolerated. Based on the results, Oncogenics is planning phase III trials of OGX- 011 in combination with docetaxel.

Pharmion announced positive results from a phase III trial of Vidaza for the treatment of myelodysplastic syndromes. This trial was designed to compare Vidaza to conventional care regimens (CCR), including best supportive care (BSC) alone, low-dose cytarabine plus BSC or standard chemotherapy plus BSC) utilized in the control arm. In the primary endpoint analysis, Vidaza was associated with a median survival of 24.4 months versus 15 months for those receiving CCR treatment, an improvement of 9.4 months with a stratified log-rank p-value of 0.0001. Two-year survival rates were 50.8% versus 26.2% for subjects receiving Vidaza versus CCR (p<0.0001). Based on the results, Pharmion plans to file a MAA in Europe and a sNDA in the US by the end of 2007.

July 9, 2007

Millennium reported positive results from a phase III trial of Velcade for the treatment of multiple myeloma. This randomized comparator trial enrolled 480 subjects who received Velcade in combination with dexamethasone or vincristine, adriamycin and dexamethasone (VAD) prior to stem cell transplantation (SCT). Velcade was dosed at 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle and dexamethasone was dosed at 40 mg on days 1 through 4 during cycles one through four and on days 9 through 12 during cycles one and two only. Subjects on VAD therapy received four cycles with vincristine at 0.4 mg/m2 on days 1 through 4; adriamycin at 9 mg/m2 on days 1 through 4; and dexamethasone 40 mg on days 1 through 4, days 9 through 12 during cycles one through four and on days 17 through 20 during cycles one and two only. As induction therapy, the subjects receiving Velcade showed a complete response (Cr) rate of 20% compared to 7% for VAD. After SCT, Velcade demonstrated a CR rate of 43% and a very good partial response + CR (VGPR + CR) rate of 75%. VAD showed a CR rate of 28% and a VGPR + CR rate of 46%. Based on the results, Millennium plans to advance Velcade as a front-line treatment for multiple myeloma.

April 18, 2005

Celgene reported positive interim results of a pair of parallel phase III trials of Revlimid (lenalidomide), for the treatment of multiple myeloma. Trial data have yielded strong evidence of superiority, with a median time to progression of at least 15 months for the US study and more than 11 months for the international study, vs. only 5 months for subjects receiving dexamethasone alone. This superiority was highly statistically significant (p<0.00001), and the duration and number of ongoing responses mean that the primary endpoint, which was to characterize the overall time to progression, cannot yet be calculated. Clinical responses were observed in 51.3% and 47.5% (respectively by trial) of subjects receiving combination therapy with the drug, vs. 22.9% and 18.4% of subjects receiving dexamethasone monotherapy (p=0.001). Both studies were randomized, double-blinded, placebo-controlled trials which enrolled relapsed or refractory multiple myeloma patients; these patients were randomized 1:1 to receive Revlimid plus dexamethasone (combination therapy) or dexamethasone alone. One trial enrolled 354 subjects across 47 US sites, while the other enrolled 351 subjects across 50 international sites. These ongoing trials are being conducted under a Special Protocol Assessment with the FDA, and will form the basis of both NDA and MAA submissions.

CureTech issued results of a phase I trial of their investigational monoclonal antibody CT-011, for the treatment of hematological malignancies. Trial data yielded positive safety indications, with no significant adverse events noted and a positive overall toxicity profile: no dose-limiting toxicities were observed, the most common adverse events were mild allergic reaction and low grade fever, and single-administration maximum tolerated dose was not reached. Preliminary evidence of clinical response was also observed in 5 subjects, with 1 partial response (including platelet transfusion independence) through 8 months, 2 incidences of stable disease through at least 7 months, and 2 minimal responses. This open-label escalating dose study enrolled 17 subjects with advanced refractory hematological malignancies at the Chaim Sheba Medical Center in Tel-Hashomer, Israel. Subjects received a single 5-hour intravenous infusion of escalating doses of the drug, and were followed for safety, tolerability, and evidence of disease progression.

Lorus Therapeutics has reported preliminary results of a phase II study of GTI-2040, their investigational ribonucleotide reductase R2 inhibitor, for the treatment of renal cell carcinoma. Results from the study yielded evidence of efficacy, with 52% of subjects experiencing disease stabilization or better, including 1 patient with a 23% reduction in tumor burden and disease stabilization through 10 months and 1 partial response, a 39% reduction in tumor burden and disease stabilization through 8 months. This open-label study enrolled 33 patients with advanced metastatic renal cell carcinoma across 7 US sites, who received combination therapy with GTI-2040 and capecitabine, an approved chemotherapeutic. The trial was co-sponsored by the National Cancer Institute.

December 13, 2004

BioCryst Pharmaceuticals announced additional data from both phase I and phase I/II clinical trials of forodesine hydrochloride, their investigational Purine Nucleoside Phosphorylase (PNP) Inhibitor for the treatment of several types of leukemia and lymphoma. Results from the phase I study demonstrated pharmacokinetic activity, with a near-total inhibition of PNP at a dose of 40 mg/m2. Evidence of efficacy in treating subjects with cutaneous T-cell lymphoma was also observed, with 9 out of 13 patients showing improvement in skin and/or a pharmacodynamic response (including 3 complete responses and 1 partial response). Furthermore, two patients who received forodesine continued to show evidence of clinical activity through 9 -11. Results from the phase I/II study indicated that the drug was well-tolerated in all patients at all dose levels. 7 of the 15 patients treated demonstrated a decrease in tumor burden, and 2 patients also showed normalization of bone marrow precursor elements. Both studies were multi-center dose-escalating trials; the phase I study enrolled 13 subjects with cutaneous T-cell lymphoma, and the phase I/II study enrolled 15 subjects with mixed hematological malignancies. Based on these results, BioCryst recently initiated a phase I trial in CTCL patients using an oral formulation of forodesine.

Bristol-Myers Squibb reported results of a phase I trial of BMS-354825, for the treatment of chronic myelogenous leukemia (CML). Results from the study demonstrated significant efficacy in treating chronic, accelerated and blast-phase CML: 86% of the chronic phase patients demonstrated complete hematologic response, and 75% and 79% of the accelerated and blast phase patient groups demonstrated some degree of hematologic response. Cytogenetic responses were observed in 28%, 0%, and 53% of patients, respectively. This ongoing, open-label study has enrolled a total of 65 subjects with imatinib-resistant or –intolerant Philadelphia chromosome positive CML at a single US site. The company has announced the intention to initiate phase II development as soon as possible, following successful completion of this trial.

Celgene announced final results from a phase III trial investigating their approved drug Thalomid (thalidomide) for the treatment of multiple myeloma. Results from the study indicate that the addition of Thalomid to standard dexamethasone therapy produced a statistically significant increase in response rate at 4 months, vs. dexamethasone alone (63% vs. 41%; p=0.002). Median time to response was similar for both regimens, at 1.1 months. Subjects receiving Thalomid did experience a significant increase in adverse events, consistent with the drug’s well-established tolerability profile. Deep vein thrombosis was the most frequent of these events. This double blind, controlled trial randomized 207 patients with previously untreated symptomatic multiple myeloma to receive Thalomid (n=103) or placebo (n=104) in addition to standard therapy with dexamethasone. The study was designed to investigate both response and toxicity. Based upon these results, Celgene announced plans to submit a request during Q1, 2005 for accelerated approval of their sNDA for Thalomid for the treatment of multiple myeloma.

Cell Genesys reported positive follow-up data from a phase II trial of their GVAX leukemia vaccine, for the treatment of acute myelogenous leukemia (AML). Data from the ongoing extension study have indicated that the drug is well tolerated, and may reduce residual leukemic cells that persist after chemotherapy. Specifically, post-vaccination declines in levels of WT-1 (a genetic marker of leukemia), were observed in blood samples of 69% of patients (11 of 16) and in 60% (12 of 20) of patients’ bone marrow samples. Furthermore, relapse-free survival was greater in the patients who showed a decrease in WT-1 levels following vaccination, compared to those who did not (80% vs. 0%, p=0.02 for blood, 90% vs. 20%, p=0.002 for bone marrow). This open-label study enrolled 54 AML patients across 4 US leukemia bone marrow transplant centers, who received autologous bone marrow stem cell transplantation and GVAX leukemia vaccine treatment following successful response to chemotherapy.

FibroGen reported results from both phase I and IIa trials of FG-2216, their investigational oral treatment for anemia. Results from the phase I study met their primary safety and tolerability endpoints, with no serious adverse events or dose-limiting toxicities. The trial also characterized the drug’s pharmacokinetic profile, noting a dose-dependent increase in serum levels of erythropoietin (EPO), a hormone which stimulates red blood cell production. Repeated doses maintained EPO elevation, which lead to a consistent increase in the number of circulating reticulocytes (young read blood cells) after three weeks of dosing. Preliminary data from the first dosing cohort (n=8) from the ongoing phase IIa study indicated that patients receiving FG-2216 experienced a increases in mean hemoglobin levels from baseline, while subjects who received placebo experienced a mean decrease; the difference between the FG-2216 and placebo groups was statistically significant at both 3 (p = 0.024) and 6 (p=0.025) weeks. The open-label phase I trial enrolled 54 healthy male volunteers, who received dose-escalating single or multiple doses of the drug for up to 3 weeks. The phase IIa trial is one of several ongoing single-blind, placebo controlled studies designed to evaluate the safety and efficacy of FG-2216 in anemic patients suffering from chronic kidney disease, including both EPO naïve and EPO experienced individuals.

Icagen announced positive results of a phase II study of ICA-17043, for the treatment of sickle-cell anemia. Trial data met their primary efficacy endpoints, with a dose-dependent increase in hemoglobin level from baseline; this increase was statistically significant for the high-dose treatment group (p<0.001). Secondary efficacy measures were also achieved, including increases in hematocrit and red blood cell counts, and statistically significant improvements in dense red blood cells, reticulocyte count, LDH, and indirect bilirubin. These improvements suggest that the drug reduces hemolysis and improves anemic symptoms in patients with sickle cell anemia. This randomized, double-blind, placebo-controlled, dose-range-finding study enrolled 90 patients with sickle cell anemia across 19 academic medical centers in the US, who received one of two daily doing regimens (6 or 10 mg) or placebo. It was designed to establish the efficacy of the drug in producing a change in hemoglobin level from baseline.

Novartis issued mixed results of a phase III trial of ICL670, an orally-available once-daily iron chelator, for the treatment of chronic hyperferremia (iron overload). The two high-dose regimens of the drug achieved their primary endpoint of maintaining or reducing absolute liver iron concentration (LIC), producing a highly significant reduction of -5.3 plus or minus 8.0 mg Fe/g dry weight (P<0.001), compared to baseline. This reduction was non-inferior to the reduction produced by standard therapy with deferoxamine. The two lower dose of ICL670, however, did not demonstrate non-inferiority, meaning that the overall endpoint of non-inferiority to deferoxamine for all doses was not met. The international, open-label, randomized, multicenter Phase III study enrolled 586 patients with beta-thalassemia and transfusion-related iron overload, who were randomized to receive once daily ICL670 at one of four doses (5, 10, 20 or 30 mg/kg) or deferoxamine (20-60 mg/kg/day for 5 days/week). Based on these results, Novartis announced that they anticipated filing regulatory submissions with a number of international bodies for ICL670 in the first half of 2005.

Nuvelo issued positive results of a phase II trial of alfimeprase, their recombinant thrombolytic enzyme under investigation for its potential to restore function in patient’s occluded central venous access devices (CVADs). The highest trial dose demonstrated significant efficacy in improving catheter patency, with total patency rates of 50% at 15 minutes after the first dose, 60% at 120 minutes after the first dose, and 80% at 120 minutes after the second dose, compared to rates of 0%, 46%, and 62% among patients receiving approved therapy with Cathflo Activase. This randomized, double-blind, active-controlled, dose-ranging study compared the safety and efficacy of three doses of alfimeprase (0.3 mg; 1.0 mg; and 3.0 mg) against an approved dose of Cathflo Activase (2.0 mg), enrolling 55 patients with occluded CVADs. Catheter patency was assessed at 5, 15, 30, and 120 minutes after each dose, with subsequent doses administered only if patency was not achieved after the first.

February 9, 2004

Human Genome Sciences reported negative results from a phase II trial investigating repifermin, also known as keratinocyte growth factor-2 (KGF-2) for the treatment of cancer therapy-induced mucositis. Results demonstrated the study did not meet its primary endpoint. Data showed that the percentage of subjects treated repifermin (75 mcg/kg), who experienced Grade two to four mucositis was not statistically significantly different from placebo. Repifermin was well tolerated with a safety profile similar to placebo. The study was designed to show a 40% relative reduction in the incidence of Grade two to four mucositis. The single-center, double-blind, crossover, dose-escalation trial enrolled 92 subjects with multiple myeloma, scheduled to receive stem cell transplantation. No other clinical trials of repifermin are underway or are planned in any indication.

January 5, 2004

Genmab reported positive interim results from two phase II trials investigating HuMax-CD4 for the treatment of cutaneous T-cell lymphoma (CTCL). Results showed 55% of the early stage and 38% of the advanced stage subjects achieved at least a partial response, using the Physician's Global Assessment (PGA) scale. The PGA is a comparison of baseline conditions that grades all cancerous lesions from 0 to 6. Data showed that 9% of the early stage and 23% of the advanced stage patients achieved a minor response. In addition, pruritus was improved in 82% of early stage patients and 69% of advanced stage patients. The study enrolled 11 early stage and 13 advanced stage subjects with CTCL.

Introgen reported data from a phase I clinical trial indicating that INGN 241, an MDA-7 gene therapeutic, was well tolerated and was clinically active in subjects with solid tumors. Results showed that the MDA-7 protein was detectable 4 cm away from the injection site. Intratumoral injection of INGN 241 produced protein both in local and diffusible forms. This observation was correlated with apoptosis at the external edge of the tumor that was injected. Results were reported at the 12th Annual International Conference on Gene Therapy of Cancer in San Diego. INGN 241 is currently in phase II clinical trials for the treatment of solid tumors.

Millennium Pharmaceuticals announced positive preliminary results from a phase I/II, investigator-initiated trial with Velcade (bortezomib) in combination with thalidomide with dexamethasone for the treatment of advanced stage multiple myeloma. Of the 56 subjects who are currently enrolled in the trial, 96% received prior autotransplant and 81% received prior thalidomide. Investigators reported that responses were observed in subjects who had previously received thalidomide treatment, and more than 20% of subjects achieved a complete or near complete response. Adverse events included gastrointestinal events, fatigue, peripheral neuropathy and hematologic toxicities. Results were reported at the 45th Annual Meeting of the American Society of Hematology (ASH) in San Diego.

June 30, 2003

INEX Pharmaceuticals reported final results from a phase II/III trial investigating Onco TCS, a liposomal encapsulated vincristine for the treatment of relapsed aggressive non-Hodgkin's lymphoma. Results showed the overall response rate was 25%, including seven subjects (6%) whose tumors were completely eliminated and 23 subjects (19%) who achieved a greater than 50% reduction in tumor volume. Data also demonstrated that 31 subject (26%) treated with Onco TCS had their disease stabilized. The median duration of response was approximately three months from first documentation of response as measured by a computed tomography (CT) scan. The study enrolled 119 subjects and was designed to test the treatment as a single-agent therapy. Subjects had previously received on average four other therapies and 72% had treatment resistant disease.

Millennium Pharmaceuticals reported positive results from a pivotally phase II trial investigating Velcade (bortezomib), now approved for the treatment of multiple myeloma. Results demonstrated that a majority of subjects achieved a reduction or stabilization of their disease severity, with some experiencing a complete response. Data showed that 67 subjects (35%) had a complete, partial or minimal response to treatment with Velcade. The overall median survival rate was 16 months and the median duration of response was 12 months. The multi-center study enrolled 202 subjects with relapsed and refractory multiple myeloma who had averaged six prior therapeutic regimens for their cancer. Subjects received 1.3 mg/m2 of Velcade (bortezomib) for Injection for up to 24 weeks. Study results were reported in the New England Journal of Medicine.

January 27, 2003

Amgen reported positive results from a phase III trial investigating rHu-KGF, a natural keratinocyte growth factor for the treatment of oral mucositis as a complication of cancer treatments. Preliminary results from the randomized, double blind trial were positive on all endpoints showing a highly significant decrease in both the duration and incidence of severe mucositis. In addition, results showed that the drug was well tolerated. The study enrolled subjects who underwent bone marrow transplantation treatment for hematologic malignancies such as lymphoma, multiple myeloma, and leukemia.

July 15, 2002

Interim data from an ongoing phase I/II trial indicates that Celgene's Actimid (CC-4047) has an acceptable toxicity profile and produces anti-tumor activity in multiple myeloma subjects. The ongoing, dose-escalation trial included 18 subjects with relapsed or refractory multiple myeloma. All subjects had been heavily pre-treated with a median of three courses of chemotherapy, and 22% of subjects had received prior thalidomide therapy. Results showed that eight subjects achieved stable disease, seven experienced a reduction in M-protein of between 25 and 50%, and three experienced a reduction in M-protein of greater than 50%. Dose limiting toxicities observed in the trial were neutropenia and thrombosis.

January 21, 2002

Phase I/II trial results indicate that Celgene's Revimid produces anti-tumor activity and is generally well tolerated. The open-label trial included 24 evaluable subjects with rapidly advancing refractory multiple myeloma. Sixteen of these subjects had failed thalidomide treatment, and all had failed at least two prior regimens. Subjects received one of four Revimid doses (5 mg/day, 10 mg/day, 25 mg/day or 50 mg/day). Data showed that 19 subjects (79%) achieved a minimum of stable disease, and 63% experienced a greater than 25% reduction in paraprotein.