Replies to post #80696 on Biotech Values

[mcbio]

RIGL - Thoughts on TASKi2 Results

Well, the results were what I thought they would be and the stock behaved pretty much as I expected. R788 is clearly efficacious in treating RA as this trial showed. Investors still apparently have concerns about the safety, although I thought this trial continued to show that the side effects (hypertension, diarrhea, neutropenia) in a small number of patients appear to be manageable either via an increase in blood pressure medication or dose reduction of R788. It's important to note that these side effects aren't much greater than those observed in the placebo patients who had failed methotrexate treatment.

I am going to wait until the TASKi3 results are revealed in a few weeks before I add to my RIGL position as I don't think even positive results from this trial will get the stock moving. I believe it's going to take RIGL getting a lucrative partnering deal for R788 for this to occur and, if this is to occur, it would be sometime after the TASKi3 results are released assuming those results are positive. Note that TASKi3 is testing R788 in patients who have failed an existing biologic.

I welcome thoughts from you all on the safety of R788 and RIGL in general.

[mcbio]

RIGL - Phase 2b TASKi3 Results Revealed

(full PR text posted for archival purposes)

http://finance.yahoo.com/news/R788-in-TASKi3-Clinical-Trial-prnews-911912000.html?x=0&.v=1

R788 in TASKi3 Clinical Trial Does Not Meet Efficacy Endpoints in RA Patients Who Had Previously Failed Biologic Therapies - Results Incongruent

Bone MRI Scans Show Improvement; Safety Results Consistent with TASKi2

SOUTH SAN FRANCISCO, Calif., July 23 /PRNewswire-FirstCall/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL - News) today announced that in the TASKi3 Phase 2b clinical trial in rheumatoid arthritis (RA) patients who had failed to respond to at least one biologic treatment, the group treated with R788 (fostamatinib disodium) did not report significantly higher ACR 20, ACR 50, ACR 70 and DAS28 response rates than the placebo group at three months, and therefore, the trial failed to meet its efficacy endpoints. The objective components (CRP and ESR)* of these ACR scores did show a statistically significant difference; however, the subjective reported response rate components did not as compared to placebo. Although the ACR scores for the R788 group were within the expected range in this patient population, the reported placebo response rates were considerably higher than seen in any other previous study of RA biologic failure patients and rose unaccountably between week 6 (at which point the reported response rates between R788 and placebo were significantly different) and month 3 (when such reported response rates were no longer significantly different).

TASKi3 was the first clinical trial evaluating R788 in which anatomical changes in the patients' wrist and hands were evaluated using Magnetic Resonance Imaging (MRI) and scored using the RAMRIS (Rheumatoid Arthritis Magnetic Resonance Imaging Scoring) system. Those results showed improvements in the treated group versus the placebo group in the Synovitis and Osteitis scores, while the Erosion scores, known to be the slowest to change, showed no significant effect at three months. The most frequent adverse events were as expected from the earlier TASKi trials and appear to be manageable.

Rigel will host a conference call today at 7PM EDT/ 4PM PDT to discuss these results (see conference call details below).

"Our objective with R788 in RA is to position the product after methotrexate and before biological therapies are used. We have shown excellent results in that patient population in our earlier TASKi1 and TASKi2 studies, and we believe that patient population represents the large market opportunity for this product," said James M. Gower, chairman and chief executive officer of Rigel. "In this TASKi3 patient population, biologic failures, we have seen divergent results as sometimes happens in studies with subjective components. However, we are pleased to see excellent results in the objective measures and in the Synovitis and Osteitis MRI scores," he added.

*blood measurements of C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR)

[See Release for Actual Table]


MRI Results

[See Release for Actual Table]

Safety Results

Similar to TASKi2, the most common clinically meaningful drug-related adverse events noted in TASKi3 were diarrhea and hypertension. Dose reduction options were pre-specified in the trial protocol and, in cases where doses were reduced, patients generally completed the clinical trial with minimal safety issues. The most common adverse events in the trial overall were related to infections, though these were generally evenly distributed among the placebo and active dose group.

The mean increase in blood pressure from baseline at 3 months, using a last observation carry forward methodology, was 3.2-3.6 mmHg for the 100 mg bid dose group. In TASKi3, approximately 17% of patients in the 100 mg bid dose group had blood pressure medication adjusted or in some cases initiated during the course of the clinical trial, compared to 8% of the placebo patients. For those patients who had their dose of blood pressure medications adjusted or initiated, their blood pressure was successfully reduced and their blood pressure was generally well controlled throughout the trial. The blood pressure medications were standard doses of common blood pressure medications such as ACE inhibitors or diuretics.

"For this patient population, patients who failed biologic therapies, their bones and joints appear to respond to R788, but the objective and subjective components of the ACR and DAS28 scores are incongruent, mainly because the reported subjective placebo response rates were higher than expected," said Elliott Grossbard, M.D., chief medical officer for Rigel. "Nonetheless, R788 is well tolerated and its side effects appear generally manageable, and we look forward to planning our Phase 3 program for R788 with a corporate partner," he added.


Safety Results Tables

[See Release for Actual Table]

TASKi3 Treatment Emergent Adverse Events

[See Release for Actual Table]

Mean Blood Pressure (Systolic/Diastolic in mmHg)

[See Release for Actual Table]

Trial Design

TASKi3 was a 3 month, multi-center, randomized, double blind, placebo controlled, parallel dose clinical trial involving 219 RA patients in the U.S. who had failed to respond to at least one biologic treatment (such as TNF inhibitors). The patients were randomly assigned to two cohorts and thus received R788 orally in a 100 mg bid (twice daily) dose or placebo for a period of up to 3 months. Patients were assigned on a 2:1 basis to R788 or placebo. Throughout the clinical trial period, all of the patients continued to receive their stable dose of methotrexate.

Efficacy assessments for each participant were based on the American College of Rheumatology criteria, which denotes at least a 20% (ACR 20) improvement, at least a 50% (ACR 50) improvement, or at least a 70% (ACR 70) improvement, from the baseline assessment at the end of the 3 month treatment period. The ACR measurement factors included reported physician and patient global assessment of disease activity, patient reported pain score, and any change in CRP in the patient's blood. The primary efficacy endpoint for the clinical trial was the percent of patients assigned to the R788 100 mg bid dose who were ACR 20 responders at the end of 3 months. Secondary efficacy endpoints included other ACR scores and, a comparison of response rates for the R788 100 mg bid dose versus placebo as determined by MRI using the modified RAMRIS scoring system of wrists and hands at baseline and at month 3.

R788 and RA

RA is a progressive, painful and potentially debilitating disease, that affects more than 2 million people in the U.S. It is a chronic inflammatory disease that puts the body's immune system into overdrive where it ultimately causes inflammation in the joints and destroys soft tissues, cartilage and bone. Rigel's R788 is a novel, orally available syk kinase inhibitor designed to interrupt the cellular signaling at the trigger point of inflammation, thereby stopping the progression of the disease. In July 2009, Rigel announced results from its Phase 2b TASKi2 clinical trial showing significant improvement in RA patients treated with R788 who had failed to respond to methotrexate treatment.