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AACR 2007 Highlights
Dendreon (Reduce 2 Rated)
In a poster presentation, Dendreon shared immune monitoring data from its
ongoing P-11 trial for Provenge, a novel active cellular immunotherapy now
pending FDA approval (PDUFA is May 15) for use in hormone-refractory
prostate cancer (HRPC). P-11 evaluates the potential of Provenge in “upstream”
use for hormone-sensitive prostate cancer (HSPC), a much larger market
opportunity (company estimates there are roughly 56,000 patients with HRPC,
but ~380,000 with HSPC).
The data were very much similar to that found in the abstract made available
prior to the conference, and confirm previously announced data from other
Provenge trials. In essence, the data suggested that Provenge could elicit a
prolonged immune response in patients with HSPC in that: 1) the change in
PA2024-specific proliferative responses from baseline to weeks 4 and 13 were
significant for Provenge across three different antigen concentrations compared
to placebo (p<0.0001); and 2) at the time of the booster infusion (ranged from 4-
33 months), the immune response was still significantly higher for the Provenge
arm than the placebo arm.
While the data are supportive of potential use of Provenge in the HSPC setting,
we note that P-11 is a non-registrational Phase III trial, for which Dendreon
is not likely to be able to file with FDA as proof of efficacy should it wish to
pursue this indication. Dendreon is still collecting data from P-11 (enrollment
was complete in 2005), and we await results on PSA doubling times and timeto-
bone metastases in order to better assess the potential of Provenge in HSPC.
While it remains difficult to estimate when final data will be available (survival
data won’t be available for several years), we believe additional data may be
presented at the upcoming AUA and ASCO meetings (May 19-24 and June 1-5,
respectively).
KOL Feedback on Provenge’s Potential Approval was Very Cautious
Attendance at the AACR meeting gave us a unique opportunity to gather
feedback from various experts in the fields of immunotherapy and prostate
cancer on their general thoughts on Provenge and their views on whether
Provenge should be approved on May 15.
Overall sentiment on Provenge’s chances of being approved next month
was negative, with no particular bias between immunotherapy and prostate
cancer key opinion leaders (KOLs). On the positive side, despite the setbacks of
previous immunotherapies, KOLs were still enthusiastic on the potential of
immunotherapy in treating cancer, and while it was likely that Provenge might
not be approved on time, sentiment was best summarized by comments by a
thought leader from Memorial Sloan-Kettering Cancer Center (New York) who
said it was “important not to throw the baby out with the bathwater.” Provenge
P-11 data is supportive of Provenge’s
potential in hormone-sensitive prostate
cancer, but more data is needed
KOL feedback reinforce our view that
an approvable letter for Provenge is
likely on May 15
US Small/Mid Cap Biotechnology 23 April 2007
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was viewed as an important advance, with additional efforts and investment
necessary and warranted, but it might be some time before definitive proof on
Provenge might be available.
KOLs we spoke with felt that while the data were encouraging, one
problem with Provenge was that they still didn’t know enough about the
therapy itself to feel comfortable.
Issues and concerns raised by thought leaders about Provenge included the
following:
■ Uncertainty surrounding Provenge’s exact mechanism of action by which it
mediates an anti-cancer effect.
■ Lack of proof that Provenge has any direct effect at all on the cancer/tumor.
■ Immune responses seen to date appear to be directed towards the PA2024
PAP fusion protein, not the native PAP prostate antigen itself (a response
directed towards the latter is much preferred).
■ It remains unclear whether the benefit being attributed to Provenge could
simply be attributed to GM-CSF (which is an important component in
Provenge).
■ To date, Dendreon has shown that the Provenge immune response is more of
a CD4+-mediated effect, when ideally a CD8+-mediated response (direct
killing of tumor cells) is preferred.
■ Other adjuvants besides dendritic cells would be preferred.
■ The clinical trial program would have been more ideal if the company had
generated more meaningful and more easily interpreted/understood Phase I/II
data before moving into Phase III.
As it relates to approvability on May 15, the KOLs felt that there just
wasn’t enough conclusive evidence at the current time to prove Provenge’s
efficacy, and that more clinical data were required before potential FDA
approval. Comments were:
■ All “serious medical oncologists” do not believe the efficacy data presented
are robust enough to allow FDA to approve Provenge.
■ While it may be difficult politically speaking, at the end of the day, the FDA
will have to go against the advice of the advisory panel (remember, the vote
by the advisory committee is only a recommendation).
■ Many oncologists agreed with the negative contents of a recent letter written
by Dr. Howard Scher (Memorial Sloan-Kettering Cancer Center) to FDA on
the flaws in the Provenge clinical data. (Dr. Scher is a leading authority in
prostate cancer, and he was one of four who voted “no” on the efficacy
question for Provenge at the March 29 advisory committee meeting.)
We believe this provides additional support behind our cautious view on the
Provenge BLA filing, where we continue to believe that the existing clinical
Provenge still a mystery to many
thought leaders
KOLs don’t see an approval likely as
more conclusive data are needed
US Small/Mid Cap Biotechnology 23 April 2007
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data available data for Provenge, while suggestive of efficacy, are not robust
enough to warrant FDA approval on May 15.
Thus, we reiterate our view that Provenge will be the subject of an
approvable letter from FDA by or on Provenge’s May 15 PDUFA, and that
Dendreon will need to submit additional clinical trial data (from the
ongoing IMPACT/D9902B study) before ultimate FDA approval can be
secured.
