SOUTH SAN FRANCISCO, Calif., June 3 Rigel todayreported an abstract providing preliminary results of a Phase 2 clinical trialof its oral Syk inhibitor, R788 (fostamatinib disodium), in patients withrelapsed or refractory B-cell non-Hodgkin's lymphomas (NHL). The abstractreports favorable responses for patients suffering from small lymphocyticlymphoma/chronic lymphocytic leukemia (SLL/CLL) or from diffuse large B-celllymphoma (DLBCL), particularly in view of the advanced and refractory stage ofthe disease in the treated patients. Furthermore, R788 appears to be welltolerated in this patient population. More studies of the drug candidate inthese subsets of NHL are being planned. These results, with additionaloutcomes and follow-up, will be presented at the 10th International Conferenceon Malignant Lymphoma in Lugano, Switzerland later this week.
Rigel will host a conference call today at 8:00 a.m. EDT to discuss theseresults (see conference call details below).
"The results of this study suggest that modulating the B-cell signalingpathway with R788 may represent a new therapeutic approach to non-Hodgkin'slymphoma particularly in DLBCL and SLL/CLL," said Elliott Grossbard, M.D.,executive vice president and chief medical officer of Rigel. "As an oral agentthat is believed to be well tolerated, R788 may become an attractiveadditional therapeutic option in these cancers."
At two months of therapy, 53 of the 59 patients were evaluated. Fivepatients (8% of enrolled) were withdrawn due to possibly related adverseevents such as cytopenias and diarrhea, and one for non-compliance. Overall,as of January 15th, 44% of patients had been in the trial for over 7 monthswithout progression of disease. The study is continuing and further resultsover longer periods of treatment will be available later in the year.
The study was conducted in two Phases. In Phase 1, a small group ofpatients were studied and the 200 mg PO bid (oral, twice daily) dose wasselected for further study. In Phase 2, 59 patients with B-cell NHL wereenrolled and were given R788. Prior to enrollment, all patients had receivedvarious standard of care treatments for their disease, including CHOP (a drugcombination) and possibly Rituxan, and had failed to respond to thosetherapies or suffered a relapse of the disease. The median age was 62 yearsold. Roughly equal numbers of patients were enrolled based on their subtype oflymphoma, which included: DLBCL, follicular lymphoma (FL) and othernon-Hodgkin's lymphomas (specifically - SLL/CLL, MCL, MALT, andlymphoplasmacytic).
B-cell Lymphoma and Syk Inhibition
Lymphoma is the name given to a variety of blood cancers that result whenlymphocytes, or white blood cells, grow uncontrollably and build up in thelymphatic system and bone marrow giving rise to malignant tumors. Theuncontrolled growth is, in part, mediated by the Syk enzyme, which signals thegrowth/survive mechanism of the aberrant cells. By inhibiting Syk, thatsignal is curtailed and the aberrant cells cannot proliferate.
In 2006, lymphoma affected an estimated 500,000 people in the UnitedStates, with 332,000 of them suffering from NHL varieties of the disease.Diffuse large B-cell lymphoma is the most common type of NHL and is generallycategorized as aggressive, marked by rapidly growing tumors in the lymphnodes, spleen, liver, bone marrow and other organs.
A variety of treatment options exist, including chemotherapy andradiation, but the five-year survival rate for NHL patients is estimated to bearound 50%. Even for those who respond to treatment, recurrence of the diseaseis common.
Conference Call Information
Rigel will host a conference call to discuss the lymphoma results today,June 3, 2008, at 8:00 a.m. EDT/5:00 a.m. PDT. To access the live call, pleasedial 866-356-3095 (domestic) or 617-597-5391 (i