on Tuesday halted a phase III trial in light of positive interim results for its Velcade in patients with newly diagnosed multiple myeloma.
The news garnered Millennium a 9% hike in share price, but the question remains: Will the IV-administered treatment emerge as the standard of care next to
oral Revlimid, which has promising efficacy of its own? Speculation will rule until efficacy data are revealed at the American Society of Hematology meeting in December.
The 682-patient study, which gauged Millennium's Velcade plus melphalan and prednisone in comparison to a melphalan and predisone control arm, was stopped early on the recommendation of an independent data-monitoring committee to allow the control arm the benefit of the Velcade combination.
Millennium said the study demonstrated highly statistically significant improvement in all efficacy measures, which included time-to-disease progression (the primary endpoint), complete remission rate, progression-free survival and overall survival compared to the control arm.
The company plans to file a supplemental new-drug application for patients with newly diagnosed myeloma, and Millennium says such an approval would double the number of patients eligible to receive Velcade, which is already approved for patients who've received at least one prior therapy. It will announce one-year survival data from this study in December at ASH.
The fact that the trial met the efficacy endpoints early on, prompting the data-monitoring committee to recommend stopping the study can only be interpreted as good. But analysts are still questioning whether doctors and patients will adopt it as the first-line standard of care amid tough competition.
Celgene's Revlimid with dexamethasone, in a 450-patient phase III study, had a 96% overall one-year survival and a 92% overall two-year survival rate.
Millennium presented data from a 54-patient phase I/II trial on Velcade plus melphalan and prednisone in June that had a complete remission rate of 43%, an overall one-year survival rate of 92%, and a three-year overall survival rate of 85%. The data that will be announced in December on the phase III VISTA study will likely be weaker as the outcomes in larger studies are typically more modest than smaller, early stage studies, according to Citi analysts in a report Tuesday. If this is true and results are more modest, they would fall shy of the efficacy displayed in Celgene's aforementioned phase III trial.
Also, a phase II, 54-person study of Revlimid plus melphalan and prednisone showed that combination had a 48% complete response rate and a 100% one-year overall survival rate. Similar to its predictions for Velcade, data from a larger phase III study on Revlimid may be more modest. But, notably, everything is more modest when you start with 100%.
A summation: "Velcade is clearly an active second- and third-line agent, but surpassing Revlimid's one-year survival rate of 96% (the phase III results for Revlimid plus dexmethasone) and 100% (the phase II trial on Revlimid plus melphalan and prednisone) may be difficult," noted Lazard analyst Matthew Osborne in a report Tuesday. And Osborne notes the second concern, "If superior to Revlimid, Velcade's efficacy would ultimately have to be considered against Revlimid's oral dosing advantage."
The question: Why would doctors and patients choose an infusion over an oral alternative?
In answer to this, CEO Deborah Dunsire told
that physicians appreciate the compliance of the less-frequent infusion treatment and that with an oral treatment, "you don't know that your patients are taking it every day as they should."
Still, she predicts it is function over form that will matter. "At the end of the day, it is going to be the combination of agents that deliver the highest efficacy to the patients," she said.
Millennium shares added 88 cents, or 9%, to $10.65; and Celgene climbed $1.54, or 2%, to $69.29 Tuesday.