PiperJaffary on CELG /Velcade /REVLIMID
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...Velcade Interim Frontline Phase 3 Data Expected In 2H06. One study led by Mateos testing Velcade in combination with MP
(n=53) in patients not eligible for transplant demonstrated an overall response rate of 86%, with 43% of patients attaining a CR or nCR
(30% with CR only) after a median of 5 cycles. This response rate is very encouraging, suggesting this Velcade combination could
have slightly better efficacy than MP/Thalomid (we believe it is too early to say how this regimen will fair compared to Revlimid/MP),
although additional data from a controlled study will be important to confirm the high CR rates, as well as to assess time to
progression. To this end, Millennium is sponsoring a large Phase 3 trial, comparing MP with or without Velcade in patients not
eligible for transplant. This study (known as VISTA) was initiated in January 2005 and we expect enrollment will complete shortly.
Millennium expects to present data from Phase 3 trial for Velcade in MM in 2H06. Based on the size of the trial (similar in size to
APEX which took 14 months to enroll), we expect partial time to progression data could be available for the ASH meeting in late
2006.
...
Refractory MM
Revlimid Could Disrupt Near Term Velcade Use In Relapsed/Refractory Multiple Myeloma. In 2003 Velcade was approved for
the treatment of multiple myeloma in patients who had received at least two prior therapies, based on single agent response rates of
28%-30% and CRs of ~4% in two open label Phase 2 trials (SUMMIT and CREST). In March 2005, Velcade's label was broadened to
include MM patients with one prior therapy based on the results from the APEX trial (n=669), which demonstrated significant
improvement in time to disease progression for Velcade vs. single agent dexamethasone (6.2 months vs 3.5 months, p<0.0001).
Millennium's most recent market research from 3Q05 indicates that Velcade penetration into the salvage market (at least 2 prior
therapies) was 40%-50% and was 30%-40% in the second line MM market. However, we expect recent Velcade market share gains,
particularly in the second line setting, to be disrupted over the next one to two years by the introduction of Revlimid. While Revlimid
FDA approval for multiple myeloma is not expected until June 2006, we expect the availability of free Revlimid through an expanded
access program (EAP) is likely to negatively impact Velcade in 1H06, driven by the impressive Phase 3 data for Revlimid in
relapsed/refractory MM that were presented in 2005. In particular, Revlimid plus dexamethasone showed time to progression of 13 to
15 months, compared to 5 months for dex alone. Overall, these patients had less advanced disease than those studied in the APEX trial
as judged by the longer time to progression for the dexamethasone control arm (5.2 months vs 3.5 months). However, when we look at
the subgroup of APEX patients that had one prior therapy, Velcade time to progression (TTP) in this group was 7.0 months,
numerically lower than Revlimid/dex (13-15 months), despite the dex control arms showing similar TTP outcomes (5.6 months vs. 5.2
months). While it is not scientifically rigorous to perform cross trial comparisons, physician feedback indicates MM experts view
Revlimid as more potent than Velcade. Moreover, the all oral regimen and side effect profile for Rev/dex is preferable to Velcade by
MM experts with whom we spoke. Additionally, physicians are very familiar with the key deep vein thrombosis (DVT) side effect
associated with Rev/dex from their Thal/dex experience. DVT rates including thromboembolism, in the Revlimid trials were
8.5%-16.4%. Interestingly, higher thrombotic event rates were seen in the North American trial, and there was a statistically
significantly higher rate in patients who received erythropoietin in both the Rev/dex and dex monotherapy arms. These rates are in line
to lower than the reported mid-teens to low-20s rates seen with Thal/dex.
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