Favrille Inc. said it will move forward with its ongoing pivotal study of FavId and the anticipated biologics license application in follicular B-cell non-Hodgkin's lymphoma, despite the drug's miss in a secondary endpoint.
An interim analysis conducted by the study's data monitoring committee reported that FavId, an active immunotherapy, failed to show statistical significance in response improvement - defined as a change from stable disease to partial or complete remission or from partial remission to complete remission - between the treatment and control groups. That analysis involved data from 233 patients who had been followed for 12 months or more.
Shares of Favrille (NASDAQ:FVRL) fell 21.8 percent Monday, losing $1.08 to close at $3.88, on concerns that the interim data could reflect results of the trial's primary endpoint, time to disease progression, which is expected to be analyzed in the second half of next year.
But Favrille President and CEO John Longenecker said the "unmet medical need here is not a reduction in response, but in a duration of response," adding that the company still anticipates positive results in time to disease progression.
The trial, which finished enrolling 349 patients in August, is designed to randomize patients with stable disease, partial remission or complete remission following four weeks of Rituxan (rituximab, Genentech Inc.) treatment to receive either FavId plus GM-CSF or placebo plus GM-CSF. Patients receive a monthly subcutaneous injection for six months, followed by an injection every other month for six months and then quarterly injections until relapse.
Blinded data from the interim analysis showed an overall response improvement rate of 41 percent - 8 percent moving from stable disease to complete remissions 12 percent moving from stable disease to partial remission and 55 percent going from partial to complete remission. Looking at the unblinded data for that 41 percent, the DMC determined that there was no statistical significance between the treatment and placebo groups.
Longenecker attributed the miss in part to the unexpectedly high overall response improvement rate, which was much higher than 27 percent seen in an earlier Phase II study. He also said the Phase III trial included a higher percentage (77 percent) of treatment-na ve patients compared to Phase II.
Favrille added response improvement to the pivotal study at the FDA's request to serve as a secondary endpoint that would "possibly give us an earlier indication of efficacy," Longenecker told BioWorld Today. "But it turned out not to be a useful endpoint."
Results of the interim analysis are not expected to delay the timing of FavId's development, which the company said is still on course to finish up in time for a BLA filing in the second half of 2007. The trial is being conducted under a special protocol assessment. Therefore, pending positive results on the primary endpoint, Longenecker said results should be sufficient for FDA review.
FavId is designed to enhance the effect of Rituxan, a passive immunotherapy that represents the market leader in NHL therapy, by stimulating the immune system to recognize the idiotype protein on the tumor and destroy the tumor cells. But most patients treated with Rituxan relapse within one to three years.
"So what we're tying to do," Longenecker said, "is train the immune system to recognize and keep that induced immune response."
San Diego-based Favrille is expected to report updated data at the American Society of Hematology meeting in Orlando, Fla., next month from its Phase II study, showing that a majority of treatment-native patients who receive FavId following Rituxan induction remained progression-free with a median of 32 months. Of the 13 patients in the trial who converted to complete remission, 12 remained progression-free with a median follow-up of 34 months.
Isis Rises On Cholesterol Data
Shares of Isis Pharmaceuticals Inc. jumped nearly 20 percent on positive Phase II data of its cholesterol-lowering drug candidate, ISIS 301012, which demonstrated promising efficacy as a monotherapy and in combination with statins.
The Carlsbad, Calif.-based firm presented data from two Phase II studies at the American Heart Association meeting in Chicago. The first study showed that patients with high cholesterol receiving statins achieved a 51 percent reduction in LDL-cholesterol when given ISIS 301012 at 300 mg/week for five weeks. Patients also showed a 42 percent reduction in total cholesterol and a 41 percent reduction in triglycerides beyond levels achieved with statins alone.
An ongoing study of ISIS 301012 as a single agent demonstrated that increasing the dose from 200 mg/week to 300 mg/week resulted in reduced atherogenic lipids and improvements in LDL-cholesterol, TC and TG of 62 percent, 46 percent and 43 percent, respectively.
The product continues to show a strong safety profile and was well tolerated in both studies.
ISIS 301012 is designed to work by inhibiting the production of apoB-100 and enabling effective add-on therapy in patients who have achieved maximal lipid-lowering on statins but have not reached their desired LDL-cholesterol levels.
Isis' stock (NASDAQ:ISIS) closed at $12.43 Monday, up $2.05.