Genentech and Biogen Idec are requesting a priority review of Rituxan (rituximab) for aggressive non-Hodgkin's lymphoma following an sBLA submission, announced Aug. 17.

The expanded indication for the biologic could be approved by February 2006, contingent upon a priority review designation.

The firms are seeking approval for front-line treatment of intermediate grade or aggressive CD-20-positive, B-cell, non-Hodgkin's lymphoma (NHL) in combination with the standard CHOP chemotherapy regimen "or other anthracycline-based chemotherapy," Genentech said.

FDA's review of the sBLA could be complicated by conflicting survival data seen among three Phase III studies submitted in support of the application.

Results from the Phase III ECOG 4494 study showed no significant benefit with Rituxan in the secondary endpoint of overall survival after a median follow-up period of 2.7 months.

However, results of two other Phase III studies - MInT ( MabThera International Trial) and LNH 98-5, conducted by GELA (Groupe d'Etude des Lymphomes de l'Adulte) - did show improved overall survival as a secondary endpoint. Roche markets rituximab outside the U.S. as MabThera.

The GELA study showed an 83% overall survival rate at one year for Rituxan plus CHOP vs. 68% for CHOP alone. The MInT study demonstrated overall survival of 95% for Rituxan plus chemotherapy vs. 85% for chemotherapy alone at two years. CHOP includes cyclophosphamide, doxorubicin, vincristine and prednisone.

Genentech previously speculated that dose intensity levels may have adversely impacted the ECOG 4494 results. The firm also maintained that a secondary, weighted analysis of the ECOG 4494 data supported improved outcomes, including overall survival.

The ECOG 4494 and GELA trials enrolled 632 and 399 elderly patients ages 60 or older, respectively, while MInT enrolled 823 younger patients ages 18-60.

MInT, the most recent trial, showed a significant improvement in the primary endpoint of time to treatment failure for Rituxan. Among patients receiving Rituxan plus chemo, 81% did not experience treatment failure at two years vs. 58% for chemo alone.

Rituxan currently is approved for relapsed or refractory, low-grade or follicular, CD-20-positive, B-cell NHL.

While a front-line NHL indication would increase Rituxan's target population by roughly 50%, the extent to which approval could boost sales remains uncertain due to extensive off-label use, according to Genentech.

Rituxan's rolling four-quarter average adoption rate for front-line, aggressive NHL was 87% at the end of the second quarter, according to the company. Rituxan generated global sales of $1.71 bil. in 2004.

Approximately 360,000 people in the U.S. have NHL - about 50% have the aggressive form of the disease, Genentech stated.

Genentech noted that it anticipates submitting a Rituxan sBLA in 2006 for use in indolent NHL induction plus chemotherapy or Rituxan following induction.

An additional filing for treatment of rheumatoid arthritis is planned this quarter, according to the company.

- Jon Dobson

Genentech/Biogen Idec Submit Rituxan sBLA For Front-Line Non-Hodgkin’s Lymphoma

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