Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : CLTX: Celsus Therapeutics -- Ignore unavailable to you. Want to Upgrade?

To: keokalani'nui who wrote (18)	8/18/2001 6:53:13 PM
From: Miljenko Zuanic	Read Replies (1) \| Respond to of 40

<<I thought they found reasonable efficacy with just a single dose.>> Yes, they THINK that they indeed did found effective single dose. <<In patients receiving Ad5-FGF4 (1010 v.p.), the mean increase in ETT time was 1.5 min at 4 weeks and 2.0 min at 12 weeks compared to 0.7 min and 1.0 min at 4 and 12 weeks, respectively, in the placebo group. Researchers also observed that patients with a shorter baseline ETT (£ 10 minutes) had a better response to active treatment than placebo.>> However, it is bit early to translate PI/II data into pivotal medical success. If ETT baseline time is ~12 min, 2.0 min increase (1 min if adjusted for placebo) is ~15%, not that great at all. I am more curious about relative data for 4, 12 and 24 weeks post dosing, in relation to ETT baseline time of ~12 min? <<To identify appropriate Ad5-FGF4 doses to carry forward into larger clinical trials, researchers used, in addition to the assessment of safety, a dichotomous qualitative method setting a response level of ETT improvement of 20% at 4 weeks and 30% at 12 weeks after treatment (each about two times placebo). Based on this analysis, in patients treated with an Ad5-FGF4 dose of 1010 v.p., 50% improved at 4 weeks and 45% improved at 12 weeks compared to improvement in 16% and 21% in the placebo group and 42% and 36% in all patients treated with the active product. >> While they did have better percentage improvement than placebo (Why placebo at all did have improvement? Selective pts???, than those in real world???) I do not think that they are medical significant. Reduce effect by placebo numbers and data are not of the magnitude that one would like to see. For instance 50% improvement for ETT of 6 min is 3 min, impressive result. But is this real situation in world that we live in? I am not cardiologist and probably can’t judge data as professional. I would like to read good report on this issue. Regards the antibody reaction (which is standard thing for AA vector), the point is can antibody neutralize gene transfer (and damage site insertion because of the non-selectivity) before angiogenic effect materialize? They claim: "Myocardial inflammation was not observed.", which is positive and indicate that there was no strong antibody reaction. They also do claim selective and strong vector uptake by cardiac cells. I like this if true. As I said, I was impressed with COO position and confidence level. However, he didn't like Schering and their speed. Nothing new here, just how bios can be frustrated when pharma take over development compound. Hope this help. Miljenko PS: <<Do they think they need multi-dose? >> NO!

To: keokalani'nui who wrote (18)	11/14/2001 6:37:55 PM
From: Miljenko Zuanic	Read Replies (1) \| Respond to of 40

Very important data for comparison (current data and future CLTX results). I am not very impressed with CVTX results (to high placebo effect???), and start to think that I was more than enough (than should be) critical in respond: Message 16229790 Miljenko CARISA results: "Study Detail The CARISA (Combination Assessment of Ranolazine In Stable Angina) study was a Phase III multi-national, randomized, double-blind, placebo-controlled, parallel group trial of the safety and efficacy of ranolazine. The clinical trial randomized 823 patients to assess the anti-anginal effects of 12 weeks of treatment with ranolazine in chronic angina patients also receiving a background anti-anginal medication. Patients received one of three background therapies (atenolol 50 mg, diltiazem CD 180 mg, or amlodipine 5 mg) and were randomized to twice daily doses of ranolazine 750 mg, ranolazine 1000 mg, or placebo. Exercise testing was performed at trough plasma concentrations (12 hours after dosing) after 2, 6, and 12 weeks and at peak plasma concentrations (4 hours after dosing) after 2 and 12 weeks. The prospectively defined primary efficacy endpoint was symptom-limited exercise duration at trough for all ranolazine patients compared to placebo at 12 weeks. The CARISA primary efficacy endpoint of symptom-limited exercise duration at trough has historically been the primary endpoint that the FDA reviews when considering anti-anginal therapies. Study Results In both ranolazine dose groups combined, symptom-limited exercise duration at trough plasma concentrations, the primary endpoint of the trial, increased on ranolazine by an average of 116 seconds, compared to an average increase of 92 seconds on placebo (p=0.012). The average increases in symptom-limited exercise duration at trough plasma concentrations on each ranolazine dose, considered independently, were 115 seconds on 750 mg and 116 seconds on 1000 mg, compared to 92 seconds on placebo (p<=0.03). The increases in exercise times on ranolazine were not significantly different among the three background therapies; insignificantly greater increases were seen over diltiazem and amlodipine than over atenolol. Statistically significant effects of ranolazine were also observed in other secondary efficacy endpoints. Ranolazine at doses of 750 mg and 1000 mg reduced the frequency of angina by an average of 1.3 and 1.7 attacks per week, respectively, compared to an average decrease of 0.6 attacks per week on placebo (p<=0.01 for each dose versus placebo). Compared to placebo, ranolazine at doses of 750 mg and 1000 mg increased the average time to electrocardiographic evidence of ischemia; these increases approached statistical significance at trough (20 and 21 seconds, respectively; p<=0.1) and achieved statistical significance at peak (41 and 35 seconds, respectively; p<0.005). In addition, compared to placebo, ranolazine at both doses statistically significantly increased the average time to onset of angina at both peak (38 seconds on each dose; p<=0.003) and trough (30 and 26 seconds, respectively; p<=0.05). Compared to placebo, systolic blood pressure after 12 weeks of treatment decreased, on average, by 2 mm Hg on 750 mg (p=NS) and by 3 mm Hg on 1000 mg (p=0.02). Average heart rate at the same time point was 1 bpm less on either dose than on placebo, differences which were not statistically significant. Side effects more common during ranolazine treatment than during placebo treatment included constipation, dizziness, nausea, and asthenia. The adverse event rate was 26% for placebo, 31% for ranolazine 750 mg, and 33% for ranolazine 1000 mg. Small (<10 milliseconds, similar to MARISA) but statistically significant (p<=0.002) increases in QTc were observed compared to placebo. Serious adverse events were observed in 6%, 7%, and 7% of patients on placebo, ranolazine 750 mg, and ranolazine 1000 mg respectively."