August 8, 2016
TiGenix and Takeda Pharmaceutical have announced 24-week results of a phase III trial investigating Cx601 for the treatment of complex perianal fistulas in patients with Crohn’s disease with an inadequate response to at least one conventional or biologic therapy. The ADMIRE-CD trial is a randomized, double-blind, placebo-controlled trial designed to investigate the efficacy and safety of a single treatment of Cx601. A significantly greater proportion of patients in the Cx601 group versus the placebo group achieved the primary endpoint of combined remission (defined as clinical assessment of closure of all treated external openings draining at baseline, despite gentle finger compression and absence of collections >2cm confirmed by MRI) at week 24 in the ITT population 53 (50%) of 107 v. 36 of 105 (34%), respectively (97.5% CI 0.230.3; p=0.024) and the mITT population 53 (51%) of 103 v. 36 (36%) of 101 (0.531.2; p=0.021). The severity of perianal Crohn’s disease was assessed at baseline and all study visits with the Perianal Disease Activity Index (PDAI). In the mITT population, the PDAI score was similar in the Cx601 and the placebo groups at baseline. The improvement in PDAI with Cx601 was significantly greater than placebo at week six, 12 and 18. In addition, the mean total PDAI score at week 24 with Cx601 (4.4) was close to the threshold for inactive perianal disease (PDAI<4) at which patients do not need medical or surgical treatment. In 2009, the European Commission granted Cx601 Orphan designation for the treatment of complex perianal fistulas in Crohn’s disease. Based on the data from this pivotal phase III trial in Europe, TiGenix submitted an MAA to the EMA in the first quarter of 2016, and a decision by the EMA could be expected in 2017. In the U.S., TiGenix intends to apply for Fast Track designation from the FDA. A pivotal phase III trial for Cx601 for the treatment of complex perianal fistulas is expected to start in the U.S. in 2017.
March 21, 2016
TiGenix reported results of a phase III study of Cx601 in Crohn’s disease patients with complex perianal fistulas with inadequate response to previous therapies. ADMIRE-CD was a randomized, double-blind, placebo-controlled phase III study. In total, 212 patients were randomized in seven European countries and Israel. Patients included in this study had an inadequate response to at least one previous therapy, including anti-TNFs. Continuation of medical standard-of-care was allowed during the duration of the trial in both groups. The study primary endpoint was combined remission at week 24, defined as closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections >2cm confirmed by MRI. This same endpoint of combined remission has been analyzed after 52 weeks as a secondary variable. In the ITT population (n=212), Cx601 achieved statistical superiority (p=0.012) with 54.2% combined remission at week 52 compared to 37.1% in the placebo arm. In the mITT population (n=204), the combined remission at week 52 was 56.3% and 38.6% for Cx601 and placebo respectively (p=0.010). Efficacy results were robust and consistent across all statistical analyses. The week 52 data also shows a higher rate of sustained closure in those patients treated with Cx601 and in combined remission at week 24 (75.0%) compared to patients in the placebo group (55.9%). Treatment-emergent adverse events (non-serious and serious) and discontinuations due to adverse events were comparable between Cx601 and placebo groups.
October 27, 2014
ChemoCentryx issued results of a phase
III study of vercirnon for Crohn’s disease. The
randomized, double-blind induction study
in patients with moderate-to-severe Crohn’s
disease enrolled 253 subjects. The primary endpoint
of the trial was the proportion of patients
with a Crohn’s disease activity index (CDAI) =
100-point response (100-point decrease in CDAI
score) at week 12. The secondary endpoint was
the proportion of patients in clinical remission
(CDAI <150) at week 12. Adult patients with a
baseline CDAI of 220 to 450, C-reactive protein
(CRP) = 3mg/L or fecal calprotectin >200μg/g
were randomized to receive either 500mg QD
or 500mg BID vercirnon for 12 weeks. Baseline
CDAI was 323 (± 56) with a range of 220-450.
Of those who completed the trial prior to the
premature study termination (n=118), the CDAI
= 100-point response at week 12 was 56% and
69% in the 500mg QD and in the 500mg BID
groups, respectively. In the same population,
remission (defined as CDAI <150) at week 12
was 26% and 36% in the 500mg QD and in the
500mg BID groups, respectively. The increase in
response and remission rates with the higher
dose of vercirnon in contrast to the lack of dose
response observed in a previous trial. There
were no safety issues observed in the trial and
gastrointestinal adverse events were not higher
in the 500mg BID group than the 500mg QD
group. There were no cardiac safety or liver
October 29, 2012
Teva Pharmaceutical released results from a phase IIa trial of laquinimod for Crohn’s disease (CD). This multi-center, randomized, double-blind, placebo-controlled study enrolled 180 patients with moderate to severe CD, based on a CD Activity Index (CDAI) of 220-450 and serum C-reactive protein (CRP) levels of >5mg/L or mucosal ulcerations evident on a recent endoscopy. Subjects received daily doses of laquinimod 0.5mg, 1mg, 1.5mg, 2mg, or placebo for eight weeks, with four weeks follow-up. Data demonstrated that laquinimod 0.5mg/day resulted in a robust, early and consistent effect on remission (48.3% versus 15.9% of patients, respectively) and response rates (62.1% versus 34.9% of patients, respectively) versus placebo. No effect was noted on remission/response at higher doses. The drug was well tolerated.
October 31, 2011
TxCell issued results from a phase I/II trial of OvaSave, an immunotherapy for Crohns disease. This 12 week, multicenter, open label, uncontrolled and dose-escalation study, CATS-1, enrolled 20 subjects with severe chronic active Crohns disease, who had failed current treatments. The subjects were placed in four dose groups and received doses of 10(6), 10(7), 10(8) and 10(9) cells injected intravenously as a single administration. In the overall population, 40% of the subjects positively responded after five weeks of treatment. In the most effective dose group, 75% of subjects responded and 38% remitted five weeks after treatment.
May 16, 2011
Centocor Ortho Biotech reported results from a phase IIb trial of Stelara for the treatment of Crohns disease. This multicenter, randomized, double-blind, placebo-controlled trial, CERTIFI, enrolled 526 previously treated subjects with moderately to severely active Crohn's disease. The subjects received Stelara administered intravenously (IV) at 1, 3 or 6 mg/kg or placebo. The primary endpoint was clinical response (at least a 100 point reduction from baseline CDAI scores) at week six. In the maintenance phase of the study, subjects classified as responders to Stelara at week six were re-randomized to receive SC Stelara 90 mg or placebo at weeks 8 and 16. At week six, 36.6%, 34.1% and 39.7% of subjects in the Stelara 1 mg/kg, 3 mg/kg or 6 mg/kg arms, respectively, achieved clinical response, compared with 23.5% of the placebo arm (p≡0.021 for Stelara 1 mg/kg vs. placebo; p≡0.057 for 3 mg/kg vs. placebo; p≡0.005 6 mg/kg vs. placebo). At week 22, 69.4% of subjects maintained clinical response with continued Stelara treatment compared with 42.5% of subjects receiving placebo (p<0.001). Clinical remission was seen in 41.7% of initial Stelara responders who continued with therapy compared with 27.4% of responders re-randomized to receive placebo (p≡0.029). Adverse events were similar overall for Stelara and placebo groups, and both IV and SC Stelara were well-tolerated.
May 10, 2010
TxCell reported positive preliminary results from an ongoing phase I/II trial of OvaSave, an autologous cellular therapy for Crohn's disease. This 12 week, open, uncontrolled, dose ranging study, dubbed CATS (Crohn's and Tr1 cells Study), enrolled subjects with severe and relapsing active Crohns disease across six sites in France. OvaSave was injected intravenously as a single administration at doses of 106, 107, 108 and 109 cells. Preliminary data show that OvaSave is well-tolerated and an encouraging efficacy signal was observed.
June 8, 2009
Enzo released positive results from a phase II trial of Alequel for the treatment of Crohns Disease. This randomized, placebo-controlled, double-blind study enrolled 43 subjects with moderate to severe disease. The subjects received either placebo or Alequel over a period of 15 weeks. The primary endpoint was the remission rate, defined as Crohn's Disease Activity Index (CDAI) score of 150 or less at two consecutive time points three weeks apart. Between weeks six and nine, 43% of the Alequel recipients met the criteria for clinical remission, versus 31% of the placebo recipients. For weeks 9 to 12, the remission increased to 50% of subjects receiving Alequel compared to 31% in the placebo group. Mean percent change in IBDQ quality-of-life score was three times greater after 15 weeks of treatment for subjects treated with Alequel compared to placebo. Treatment was well tolerated.
October 30, 2006
ChemoCentryx announced positive results from a phase II trial of Traficet-EN for the treatment of Crohn's disease. This trial enrolled 74 subjects who were randomized on a 2:1 basis to receive 250 mg of Traficet-EN or placebo, once daily for 28 days. Treatment was well tolerated. After 28 days the subjects receiving Traficet-EN had a mean decrease in C-reactive protein (CRP) blood levels of 4.4 +/- 3.7 mg/L while the subjects in the placebo group had a mean increase in CRP blood levels of 6.7 +/- 4.2 mg/L. In addition, in a defined subgroup of subjects in active flare at the time of treatment, 56% of those treated with Traficet-EN had a decrease on the Crohn's Disease Activity Index (CDAI) of 70 points versus 29% of the subjects on placebo. Overall a 100-point drop in CDAI scores occurred in 40% of those in the treatment group compared to 21% on placebo. ChemoCentryx is continuing development of Traficet-EN in ongoing phase II trials.
Osiris Therapeutics announced positive results from a phase II study of Prochymal for the treatment of moderate to severe Crohn's disease. This randomized, open label trial enrolled 10 subjects who were divided into two groups and received either low dose (2 million cells per kilogram) or high dose (8 million cells per kilogram) of Prochymal. Subjects were then evaluated for changes in the Crohn's Disease Activity Index (CDAI) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Treatment was well tolerated with no serious adverse events reported. Within 14 days of treatment, one third of the subjects had a mean reduction in the CDAI of 105 by day 28, from 341(baseline) to 236 (p=0.004). Mean IBDQ scores improved significantly from baseline to day 28 (113 to 146, p=0.008). In addition there appeared to be a correlation between dose and response, with those receiving the higher dose of Prochymal achieving a 72 point greater reduction in CDAI than those receiving low dose (CDAI reduction of 137 vs. 65). Osiris is in the process of developing and implementing a phase III program.
Xenoport reported positive results from a phase IIa trial of XP19986 for the treatment of gastroesophageal reflux disease (GERD). This single-dose, randomized, double-blind, placebo-controlled, cross-over trial enrolled subjects who received 10, 20, 40 or 60 mg single doses of XP19986 or placebo, in separate test periods with four to seven days between testing periods. On testing days reflux-provoking meals were consumed at two hours and six hours after dosing, and subjects were required to lie on their right side for two hours after each meal. Reflux was monitored continually for 12 hours using a pH/impedance probe placed in the esophagus. The median number of total reflux episodes over 12 hours after placebo treatment for the combined dose groups was 50.5 (N=44). The median change in total reflux episodes after XP19986 treatment compared to placebo treatment was -9.5 (p=0.0050). Statistically significant reductions in acid reflux episodes were seen in both the 40 mg (p=0.0498) and 60 mg (p=0.0039) dosing groups when compared to placebo in the 12 hours after treatment. XenoPort plans to move development of XP19986 forward.
August 7, 2006
Schering issued positive results of a phase II trial of sargramostim for the treatment of Crohn's disease. This multi-center, randomized, double-blind, placebo-controlled study, dubbed N.O.V.E.L. 2, enrolled 129 subjects with active corticosteroid-dependent Crohn's disease requiring 10-40 mg of prednisone or equivalent. Subjects received 6 mg/kg sargramostim or placebo via subcutaneous injection daily for 12 to 22 weeks, depending on the baseline corticosteroid dose. The primary endpoint was corticosteroid-free clinical remission (CDAI less than or equal to 150) four weeks after complete corticosteroid withdrawal. This endpoint was met, with results demonstrating that sargramostim was significantly more effective than placebo for induction of corticosteroid-free clinical remission in steroid-dependent Crohn's disease subjects.
Schering also issued negative results of a phase III trial of sargramostim for the treatment of Crohn's disease. Sargramostim is currently approved in the US under the tradename Leukine for the treatment of acute myelogenous leukemia. This multi-center, randomized, double-blind, placebo-controlled study, dubbed N.O.V.E.L. 4, enrolled 288 subjects with moderate to severe Crohn's. Subjects received 6 mg/kg sargramostim monotherapy or placebo via subcutaneous injection daily for eight weeks. The study was designed to evaluate the induction of response and remission, as measured on the Crohn's Disease Activity Index (CDAI). Response was defined as a CDAI decrease of at least 100 points and remission was defined as a CDAI score of 150 points or below. Trial results failed to demonstrate superiority in the two primary endpoints of response and/or remission at eight weeks, compared to placebo.
May 29, 2006
Microbia issued positive results of a phase Ib trial of linaclotide, for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic constipation (CC), at the DDW annual meeting. Preliminary data yielded evidence of pharmacodynamic activity in the gastrointestinal tract, as measured by markers of intestinal transit, stool consistency, stool weight, and time to first bowel movement. No evidence of systemic exposure was observed, and treatment was safe and well tolerated. Based on these data, the company announced plans to initiate phase II trials of the drug in the near future.
PDL BioPharma announced positive results of a phase I trial of Nuvion (visilizumab), for the treatment of Crohn's disease (CD), at the 2006 Digestive Disease Week (DDW) annual meeting. This multi-center open-label study enrolled 14 patients with moderate to severe non-penetrating CD, who received two doses of 10 mcg/kg Nuvion via IV bolus injection. Preliminary data yielded evidence of efficacy, with 10 of 14 subjects demonstrating clinical response (> 100 point decrease) on the CDAI diagnostic scale. 5 subjects achieved complete remission (total CDAI score <150 points) during the treatment period. Nuvion-responsive patients included 5 subjects who had relapsed on infliximab, and 2 subjects whose disease never responded. No lymphoproliferative, malignant or life-threatening adverse events were reported.
March 6, 2006
NPS Pharmaceuticals reported positive results of a phase IIa trial of teduglutide, for the treatment of moderate to severe Crohn's disease. The highest dose of the drug produced a clinical remission rate (Crohn's disease activity index score >150 points) of 36.8% at 2 weeks and 55.6% at 8 weeks; subjects receiving placebo experienced rates of 16.7% and 33.3%, respectively, though the trial was not powered to establish statistical significance between the groups. No serious treatment-related adverse events were reported. This four-arm, randomized, placebo-controlled study enrolled 100 patients, who received daily subcutaneous injections of 1 of 3 doses of the drug or placebo for 8 weeks.
October 24, 2005
UCB issued positive results of their phase III PRECISE 2 trial of CIMZIA, for the treatment of Crohn's disease, at the United European Gastroenterology Week. Trial data indicated that among subjects achieving clinical response (a reduction in Crohn's Disease Activity Index score of 100 points or more) after 4 weeks of treatment, 62.8% of subjects continuing to receive the drug through week 26 maintained this response, vs. 36.2% for subjects switching to placebo (p<0.001). In addition, 47.9% of subjects achieved clinical remission at 26 weeks, compared to 28.6% receiving placebo (p<0.001). This 26-week placebo-controlled study enrolled 668 patients with moderate-to-sever Crohn's disease. Based on these results, the company anticipated NDA and MAA filings in Q1 2006.
May 23, 2005
Centocor announced positive results of a pair of phase III trials of their approved anti-inflammatory Remicade, for the treatment of ulcerative colitis (UC). The drug was seen to produce significantly higher clinical response rates at 8 weeks in both the first (5 mg/kg Remicade: 69%; 10 mg/kg: 62%; placebo: 37%; p<0.001) and second studies (5 mg/kg: 65%; 10 mg/kg: 69%; placebo: 29%; p<0.001). The drug also produced significant efficacy in maintaining response through week 30, achieving clinical remission, promoting mucosal healing, and allowing patients to discontinue corticosteroid therapy. Each trial was a randomized, placebo-controlled study which enrolled 364 UC patients, who received one of two doses of Remicade (5 mg/kg or 10 mg/kg) or placebo on weeks 0, 2, and 6, followed by maintenance doses every 8 weeks. The first trial treated patients through week 22, with final observation at week 30, while the second ran through week 46, with final observation at week 52. These trials served to support the sNDA filing for Remicade in UC, submitted in March 2005.
Enzo Biochem announced positive results from a phase IIb trial of Alequel, for the treatment of Crohn's Disease. Trial data indicated that the drug produced significant efficacy, with 58% of subjects achieving remission, vs. 29% for placebo. Furthermore, clinical response was seen in 67% of subjects receiving Alequel (vs. 29%), and 43% of patients noted improvements in quality of life (vs. 12%). This randomized, placebo-controlled, double blind study enrolled 31 patients with moderate to severe disease, who received oral doses of Alequel or placebo for 27 weeks. Based on these results the company announced that they were planning larger, confirmatory trials.
Synta Pharmaceuticals issued result of a phase IIa trial of STA-5326, for the treatment of Crohn's disease. Trial data yielded significant evidence of efficacy, with 82% of patients in the optimal dosing group (35 mg. once daily) yielding a 70 point or greater reduction in symptom severity score on the Crohn's Disease Activity Index (CDAI). Furthermore, 64% of subjects achieved a 100 point reduction or greater, and 36% achieved a 150 point reduction. No serious adverse events were associated with treatment. This multi-center, open-label study enrolled 73 subjects into one of 5 dosing regimens (ranging from 14 mg-70 mg total daily dose) for 4 weeks. Based on these results, the company announced plans to initiate a large, randomized, double-blind, placebo-controlled Phase 2b trial by the end of 2005.
February 7, 2005
Abbott Laboratories has reported positive results of a clinical trial investigating their approved monoclonal antibody Humira (adalimumab) for the treatment of Crohn’s disease. Data from the study indicated that Humira demonstrated efficacy in treating patients whose Crohn’s disease had become refractory to standard therapy with Remicade (infliximab). Specifically, the study found that 54% (7 of 13) of subjects who received Humira experienced complete response and 31% (4 of 13) experienced partial responses, as measured by Crohn's Disease Activity Index (CDAI) score. Humira also demonstrated efficacy in treating extra-intestinal manifestations of the disease (joint pain), and in reducing patient reliance on concomitant steroid therapy. This open-label study enrolled 15 Remicade-refractory patients, of whom 13 completed the trial; subjects received an 80 mg subcutaneous initial dose of the drug, followed by 40 mg bi-weekly doses, with allowance for titration of dose to maintain response. Based on these data, further investigations of Humira for the treatment of Crohn’s disease are planned.
December 6, 2004
Isis Pharmaceuticals also issued negative results of a pair of identical phase III trials of alicaforsen, for the treatment of Crohn’s disease. Combined results from the two trials indicated that the drug did not meet its primary endpoint, with no significant increase in the incidence of remission at 12 weeks (as defined by a Crohn’s Disease Activity Index (CDAI) score of 150 or less), compared with placebo. Trial data did meet secondary safety endpoints, with a well tolerated intravenous treatment experience and no serious adverse events reported. Both trials were double-blind, placebo-controlled studies, enrolling a total of 331 subjects (151 in the US, 180 in Europe and Israel), who were randomized to receive daily intravenous doses of either 300 mg alicaforsen or placebo thrice weekly for 4 weeks. Based upon these results, Isis announced that they were discontinuing investigation of the drug for the treatment of Crohn’s disease, but still planned to move forward with development for ulcerative colitis.
Isis Pharmaceuticals issued positive results of three phase II trials of alicaforsen for the treatment of ulcerative colitis (UC). The first study compared the drug with placebo, and the results demonstrated that the drug produced significant improvements in disease activity index (DAI), a standardized measure of symptom severity, with a mean 51% reduction at week 18 and 50% reduction at week 30, compared with 18% and 11% for placebo (P=0.04, p=0.03 respectively). Furthermore, mean response duration was more than 6 months for subjects receiving alicaforsen, vs. less than 3 for placebo, and subjects experienced significant improvements in secondary endpoints, including incidence of rectal bleeding, stool frequency, and mucosal healing. The second trial compared the drug with mesalamine (standard therapy), and found that alicaforsen produced non-inferior efficacy and significantly more durable responses than the approved treatment, with average response time greater than 6 months (p<0.05). Finally the third pharmacokinetic study found that patients experienced minimal systemic absorption (<1% of dose), and 75% of subjects experienced improvements in DAI after only 6 weeks of treatment. All three trials demonstrated an excellent tolerability profile, with no discontinuations due to lack of efficacy. Both the placebo-controlled and mesalamine studies were conducted in a randomized, double-blind fashion for 6 weeks. The placebo-controlled study randomized 112 subjects in the US and Europe to receive one of four regimens of the drug via enema (nightly, 10 nightly doses then every other night, every other night, or a half dose nightly for 10 days then every other night) or placebo for 6 weeks. The mesalamine study randomized 159 US subjects to receive nightly doses of either half or full dose alicaforsen (120 mg or 240 mg) or standard therapy nightly for 6 weeks. The pharmacokinetic study was an open-label investigation, enrolling 12 subjects at one US site, all of whom received the drug once nightly for 6 weeks. The company announced plans to begin designing phase III trials for alicaforsen in UC, based on these results.
November 22, 2004
Abbott Laboratories issued positive results of a phase II study of their anti-interleukin-12 (IL-12) fully human monoclonal antibody ABT-874, for the treatment of Crohn’s disease. Results show that trial met its primary safety endpoint, with the most frequent adverse event being local injection site reaction, which occurred significantly more commonly in patients receiving ABT-874 (77 % in Cohort 1 to 88% in Cohort 2) than in patients receiving placebo (25 percent). Seven serious adverse events occurred in patients receiving the drug, but none were deemed drug-related. The trial also met its secondary endpoints, with patients in receiving the higher dose in Cohort 2 achieving significantly higher response rates compared to patients who received placebo (75 percent vs. 25 percent, p = 0.03) by the end of treatment. Clinical response was noted after three weekly injections, and the response was sustained for at least 18 weeks after treatment. Maintained response rates at week 18 and remission rates, at both end of treatment and 18 weeks, were not statistically significant in any treatment group. The randomized, double-blind trial enrolled 79 subjects into one of two dosing regimens of the drug (1 mg/kg or 3 mg/kg) or placebo on one of two seven-dose administration schedules: either with a four-week interval between the first and second injection followed by 5 weekly doses(Cohort 1) or seven weekly injections (Cohort 2).
October 4, 2004
Enzo Biochem has issued positive results from a phase II study of Alequel for the treatment of Crohn’s disease. Study results showed that the drug met its primary endpoint, with 67% of subjects receiving Alequel achieving clinical response, compared to 43% receiving placebo. Furthermore, the drug produced a significantly greater increase in quality of life (43% vs. 12%), and a greater portion of subjects receiving achieving remission (58% vs. 29%), than with placebo (the study’s secondary endpoints). Response and remission rates were established with disease severity scores on the Crohn’s Disease Activity Index, a standard measure of disease severity. The randomized, double-blind, placebo-controlled study treated a total of 26 subjects with active Crohn’s disease. Enzo announced plans to expand their phase II studies into a larger patient population.
June 7, 2004
Otsuka America Pharmaceutical and Otsuka Maryland Research Institute reported results from a phase III trial investigating OPC-6535, an oral investigational compound for the treatment of ulcerative colitis (UC). Results showed that both the 25mg and 50mg groups did not reach statistical significance compared with placebo, but did demonstrate superior clinical improvement. The randomized, double-blind, placebo-controlled enrolled 186 subjects with UC who received a once daily dose of OPC-6535 (25 or 50 mg) or placebo for eight weeks. Subjects were also permitted the use of 5-ASA products or sulfasalazine. The primary efficacy endpoint was the proportion of subjects showing a three-point reduction in Disease Activity Index (DAI) from the Baseline score to week eight. The average use of 5-ASA was 2.20 g/day. Results were reported at the 2004 Digestive Disease Week in New Orleans.
Schering AG reported positive follow up results from a phase II trial investigating Leukine (sargramostim/GM-CSF) for the treatment of Crohn's disease. Results showed that clinical response, remission, and improved quality-of-life, were maintained after drug therapy was discontinued. Data showed that 15% of subjects had a response to therapy maintained for at least six months. Leukine was generally well-tolerated and not associated with serious adverse events. The multi-center, randomized, double-blind, placebo-controlled study enrolled 124 patients Subjects were administered Leukine or placebo daily for eight weeks.<
March 15, 2004
Enzo Biochem reported early interim results of a phase II trial investigating Alequel, a complex of autologous colon-derived antigens for the treatment of Crohn’s disease. Results showed that 71% of Alequel treated subjects achieved clinical remission, defined as a CDAI score of less than 150, compared with 25% of the subjects who received placebo. In addition, data demonstrated that 71% of those who received Alequel showed a clinical response measured as a decrease of at least 70 in the CDAI score compared with 42% with placebo. The randomized, double-blind, placebo-controlled study enrolled more than 20 subjects.
February 2, 2004
Cellegy Pharmaceuticals reported preliminary results of a phase III trial investigating Cellegesic (nitroglycerin .4%), an ointment for the treatment of chronic anal fissures. Results showed the drug produced a statistically significant reduction in anal fissure pain compared with placebo, the primary efficacy endpoint of the study. Data showed that the time to 50% pain reduction with Cellegesic was a week sooner than with placebo, although not statistically significant. No significant difference was seen in tertiary endpoints, reduction of average pain over the eight-week and reduction of pain upon defecation through days 21 and 56, and healing. Most common side effects were mild to moderate headaches. The double blind, placebo controlled trial enrolled 187 subjects with chronic anal fissures.
Elan and Biogen reported positive results from a phase III trial investigating Antegren (natalizumab), a humanized monoclonal antibody for the treatment of Crohn’s disease. Results showed that the study met the primary endpoint of maintenance of response, defined by a sustained Crohn's Disease Activity Index (CDAI) score of less than 220 without rescue intervention. Data showed more than a 30% difference in treatment with natalizumab compared to placebo. The double-blind, placebo-controlled, international maintenance trial, called ENACT-2 (Evaluation of Natalizumab as Continuous Therapy-2) enrolled 428 responders from ENACT-1 (a 3-month study in patients with very active Crohn's disease). Subjects were re-randomized after 3 months to natalizumab (300 mg) or placebo administered monthly for 12 months. The primary endpoint was through month 6 of ENACT-2.
August 4, 2003
Elan reported negative results from a phase III trial of Antegren (natalizumab), a monoclonal antibody for the treatment of Crohn’s disease. Results showed that the drug did not meet the primary endpoint of response, as defined by a 70-point decrease in the Crohn's Disease Activity Index (CDAI) at week 10. Data did demonstrate however, that the time to remission and mean changes in CDAI were significantly improved with natalizumab compared with placebo. Remission was defined as a CDAI score of less than or equal to 150 at week 10. The overall rates of side effects between natalizumab and placebo treatment groups were similar throughout the study. The most common adverse events seen in the trial were headache, nausea and abdominal pain across both groups. The double blind, randomized, placebo-controlled trial, called ENACT-1 (Evaluation of Natalizumab in Active Crohn's disease Therapy-1) enrolled 905 subjects.
The BioBalance Corp. reported positive results from a clinical study investigating Probactrix, a competitor E. coli containing agent for the treatment of diarrhea and other symptoms associated with HIV infection. Results showed that Probactrix significantly reduced gastrointestinal complaints in as early as three to five days after dosing. Data also demonstrated diarrhea symptoms were markedly reduced or disappeared in the treatment arm, compared with the control group. In the treatment arm, there was significant improvement noted in bowel movement frequency during therapy, and one month after stopping administration of the drug. The drug was well tolerated with no reported side effects. The controlled study enrolled 50 subjects undergoing a standard course of HIV therapy at the Moscow Center of HIV.
May 19, 2003
Centocor and The Children's Hospital of Philadelphia reported positive results from a phase IV trial investigating Remicade (infliximab), a monoclonal antibody for the treatment of Crohn’s disease. Results showed that subjects achieved an average of 50% improvement by the second week as measured by a disease index that included pain and growth rates. All subjects achieved a clinical response, with ten subjects achieving clinical remission. The randomized study enrolled 21 pediatric subjects with Crohn’s disease at five sites in the U.S. and Europe. Subjects were between the ages of 8 and 17 years old with a history of disease for at least six months. Results appeared in the American Journal of Gastroenterology.
April 14, 2003
SangStat reported mixed preliminary results from two-phase II trials investigating RDP58, an anti-inflammatory for the treatment of ulcerative colitis and Crohn’s disease. In the ulcerative colitis study, results showed a peak response rate of 77% and a 71% remission rate among subjects taking RDP58 (200mg/day). Subjects taking RDP58 (300mg/day) achieved similar statistically significant response and remission rates. In the Crohn's disease study, although 66% of subjects treated with RDP58 (200mg/day) achieved a response, it was not a statistically significant difference from placebo. The randomized, blinded, placebo-controlled, multi-center studies enrolled a total of 231 subjects. Subjects received placebo, 100mg/day, 200mg/day, or 300mg/day of RDP58 for 28 days.
January 6, 2003
Elan and Biogen reported positive results from a phase II trial investigating Antegren (natalizumab) for the treatment of Crohn's disease. The study showed that the primary endpoint of remission at 6 weeks in the 6 mg/kg dose group, compared to placebo, was not statistically significant. However both groups that received 2 doses of natalizumab had higher rates of clinical remission than the placebo group. A significant difference in clinical responses was noted as early as week 2 and was maintained through week 12 with a maximal response of 71% in the dual 3 mg/kg dose group versus 38% in the placebo group. The randomized, double blind, placebo-controlled study enrolled 248 subjects with Crohn's disease at 35 sites worldwide.
November 25, 2002
Schering AG reported positive results from a phase II pilot study investigating Leukine (sargramostim/GM-CSF) for the treatment of Crohn's disease. Subjects treated with Leukine had a significant decrease in disease symptoms over the eight-week course of therapy as measured by the Crohn's disease activity index (CDAI), the standard measurement of treatment effectiveness. The mean CDAI decreased by 190 points, a significant improvement. The data showed that 80 % of the 15 subjects enrolled in the study responded to treatment, and 53% achieved clinical remission. Schering AG acquired Leukine from Immunex in July 2002.
September 23, 2002
Millennium Pharmaceuticals announced that the primary endpoint in its phase II study of MLN02 (formerly LDP-02) for the treatment of Crohn's disease was not achieved. In the randomized, placebo-controlled study, 185 subjects were administered either a 0.5mg/kg or 2.0mg/kg dose of ML02 or placebo at days one and 29. At 57 days, neither treatment group showed a statistically significant difference from placebo in achieving response rates as defined by a decrease of greater than 70 point on the Crohn's Disease Activity Index (CDAI). The study's secondary endpoint, disease remission, was achieved in the 2.0mg/kg (36.9%) dose of MLN02 when compared to the placebo (20.7%).
September 3, 2002
In a phase IIa study of P54 involving 27 subjects with steroid-dependent ulcerative colitis or Crohn's disease, the primary endpoint was not achieved. The main objective of the study was to determine whether or not treatment with P54 could reduce the dose of steroid required to maintain disease remission. There was a 45% reduction in steroid use for study subjects treated with P54. The same measure for the placebo group was not significantly different. However, in a sub-group of subjects whose baseline calprotectin level was below 450 mg I-1, all P54-treated subjects were able to withdraw from steroid therapy, while in the placebo group, only 44% of subjects were able to discontinue steroid use. P54 is being developed by Phytopharm.
August 5, 2002
Celltech Group announced that the results of its phase III study of CDP 571 for the treatment of Crohn's disease demonstrated that subjects treated with CDP 571 did not show statistically significant reductions in Crohn's disease activity index (CDAI) (reduction of greater than or equal to 100 points) and/or disease remission for the 28-week combined primary endpoint on an intent to treat (ITT) basis. However, statistical significance was achieved on per protocol data analysis of this endpoint. In addition, significant CDAI was demonstrated at week two and week four on an ITT basis, and the response across the 28-week period was significant compared to placebo. Results of a second study of CDP 571 for the treatment of Crohn's disease indicated that there was no significant difference between CDP 571 and placebo in the ability to enable steroid-dependent subjects to cease steroid-use while maintaining disease remission. In both studies, CDP 571 had good safety profiles.