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Provenge, zytiga and Xtandi.
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May 6, 2013
Reason for report:
PROPRIETARY - SURVEY
Howard Liang, Ph.D.(617) [email protected]
Rene Shen(212) [email protected]
Gena Wang, Ph.D.(212) [email protected]
BIOTECHNOLOGYProstate Cancer Survey Finds Robust Uptake of New HormonalAgents
• Bottom Line: MEDACorp conducted a survey of 50 US urologists andoncologists (25 in each specialty) with a majority of them practicing in thecommunity setting. The survey suggests significant use of Xtandi (MDVN[OP]/Astellas) in the pre-chemo setting already and a near-term salestrajectory that appears to be ahead of expectations. For DNDN's (MP)Provenge, the survey suggests declining use since the end of 2012.
• In aggregate, survey respondents manage twice as many pre-chemo castration-resistant prostate cancer (CRPC) patients as post-chemo patients. Together with a longer treatment duration (expectedto be 2x), the survey results suggest that the pre-chemo market is likelyseveral times as big as the post-chemo market.
• Survey finds a substantial increase of Zytiga and Xtandi of 41%and 80%, respectively, from Dec. 2012 to March 2013. The magnitudeof increase in Zytiga use matches the sequential sales growth reportedfor Zytiga. For both drugs, the growth was mainly driven by pre-chemouse and by urologists. Both Zytiga and Xtandi are projected to growsubstantially through the rest of 2013, by 84% and 167%, respectively,relative to March 2013, indicating that the market is by no meanssaturated. By physician projections, the number of patients on Xtandi willhave nearly caught up with Zytiga by the end of 2013.
• A little over half of current Xtandi patients had previously receivedZytiga, although this differed significantly between oncologistsand urologists, with the latter group having a much lower proportion ofXtandi patients post-Zytiga (28% vs. 70%) that also declined in the last3 months (from 44% to 28%). Most physicians in both specialties treat toprogression, although nearly a quarter (24%) of urologists indicated that inpost-Zytiga patients Xtandi would be continued post-progression.
• Majority of survey respondents consider the efficacy and safety/tolerability profiles of Zytiga and Xtandi to be similar in the post-chemo setting. Differences in perception by urologists and oncologistsmay be explained in part by the limited promotion of Xtandi to date tourologists. Assuming PREVAIL demonstrates a statistically significantoverall survival (OS) benefit, one-year after presumed Xtandi approval inthe pre-chemo setting, Xtandi is projected to overtake Zytiga with a 43%market share in the first-line metastatic setting vs. 34% for Zytiga. If Xtandishows only an OS trend, these shares would reverse.
• Survey respondents report declining use of Provenge sinceDecember 2012. However, Provenge usage is projected to rebound withrobust growth by the end of 2013. Although many respondents indicateddeclining use of Provenge after Zytiga pre-chemo approval and Xtandilaunch, interestingly this appears to mainly affect the casual users and tohave limited impact on existing heavy users.
S&P 500 Health Care Index: 552.34
Companies Highlighted:DNDN, JNJ, MDVN
Please refer to pages 28 - 31 for Important Disclosures, Price Charts and Analyst Certification.
SURVEY DEMOGRAPHICS
Our survey sample consists of both urologists and medical oncologists with a majority of
them practicing in the community setting. On our behalf, MEDACorp conducted a survey of 25
oncologists and 25 urologists to assess market dynamics in the treatment of castrate resistant
prostate cancer (CRPC). The survey was fielded and followed up from April 5 to April 29, 2013.
In order to get a respondent cohort that is experienced in treating CRPC, physicians had to treat at
least 30 metastatic castration-resistant prostate cancer patients personally over the past 12
months. The survey respondents are composed of 14 physicians (28%) from the academic
medical centers, 6 physicians (12%) from community hospitals, 1 physician (2%) from a VA
hospital, 27 physicians (54%) from private practice and 2 physicians (4%) from a clinic. Practice
settings were similar for oncologists and urologists in our survey.
Survey Question: What best describes your primary practice setting?
All
respondents
(n=50)
Oncologists
(n= 25)
Urologists
(n=25)
Academic medical center 28% 28% 28%
Community hospital 12% 12% 12%
VA hospital 2% 4% 0%
Private practice 54% 52% 56%
Clinic 4% 4% 4%
Other 0% 0% 0%
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
PRE- AND POST-CHEMOTHERAPY MARKETS
As expected, urologists treat a population with earlier stage disease. The surveyed
physicians treat 248 prostate cancer patients on average for a total of >12,000 patients. Of CRPC
patients, oncologists see 50 patients on average, while urologists see 63 patients on average,
though the median is closer, at 40 and 43, respectively. Oncologists see a higher number of
metastatic patients as a percentage of their overall prostate cancer practice at 53% on average vs.
16% for urologists, reflecting a generally earlier stage population seen by urologists. .
Survey Question: How many prostate cancer patients do you personally manage currently?
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Mean Median Total Mean Median Total Mean Median Total
Total (n=50) 248 155 12,396 56 42 2,804 22.6% 26.8% 22.6%
Oncologist (n=25) 94 80 2,346 50 40 1,241 52.9% 50.0% 52.9%
Urologist (n=25) 402 450 10,050 63 43 1,563 15.6% 9.6% 15.6%
Prostate cancer patients CRPC patientsCRPC as % of overall
Prostate Cancer Pts
2
BIOTECHNOLOGY May 6, 2013
In aggregate, physicians manage approximately twice as many patients in the pre-chemo
setting as in the post-chemo setting, with urologists seeing nearly 3 times as many. When
we break out the CRPC population into the 1st line metastatic (or pre-chemo), currently undergoing
treatment with 1st line chemotherapy, and post-chemo population we find that oncologists have a
higher percentage of patients (vs. urologists) in the latter two categories. On average, oncologists
are treating 20 patients in the pre-chemo setting, 16 patients in the 1st line chemo setting and 14
patients in the post-chemo setting. Urologists have 36 patients in the pre-chemo setting, 13 in the
1st line chemo setting and 13 patients in the post-chemo setting on average. For urologists, 58%
of their CRPC patients are in the pre-chemo setting compared with 40% for oncologists. In the
post-chemo setting, oncologists have 29% of their patients fitting this criteria compared with 21%
for urologists. This highlights the change in prescriber base that occurs as medications such as
Zytiga and eventually Xtandi move from the post-chemo to the pre-chemo space.
Survey Question: How many of your castration-resistant prostate cancer (CRPC) patients
are in the following categories?
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
ZYTIGA, XTANDI UTILIZATION TRENDS
Survey respondents, especially urologists, report a substantial increase in their use of both
Zytiga and Xtandi from December 2012 to March 2013. Though urologists on average had
fewer patients on Zytiga or Xtandi in December, they increased their usage of these agents by
76% and 209%, respectively, in 1Q:13. Oncologists also increased their usage of the two agents,
though by a more modest percentage (18-36%). In aggregate, the average number of patients
receiving Zytiga increased from 5.6 at the end of December 2012 to 7.9 at the end of March,
representing a 41% increase. The average number of patients receiving Xtandi in our survey
sample increased from 2.5 at the end of December 2012 to 4.6 at the end of March,
corresponding to an 80% increase. JNJ (OP) reported a 41% revenue increase sequentially for
US Zytiga sales in the 1Q:13, equal to the 41% reported by our survey respondents. However,
there were inventory adjustments in the 4Q:12 for Zytiga sales that impacted the comparison. IMS
script data had only a 14% increase sequentially. Furthermore, as the urologists and oncologists
reported drastically different growth rates for Zytiga in our survey, the mix of specialty will be an
important factor when determining the growth rate.
Mean Pre-Chemo 1st Line Chemo Post-Chemo Pre-Chemo 1st Line Chemo Post-Chemo
Total 28 15 14 50% 26% 24%
Oncologists 20 16 14 40% 32% 29%
Urologists 36 13 13 58% 22% 21%
# of patients by line of therapy % of patients by line of therapy
3
BIOTECHNOLOGY May 6, 2013
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Overall use of both Zytiga and Xtandi saw substantial increase in the pre-chemo setting
while post-chemo use held steady or had a more modest increase. In the pre-chemo setting,
the average number of patients increased from 2.6 for each respondent in December 2012 to 3.9
in March 2013 (+50%), following the FDA approval in this setting in December 2012. Although
Xtandi has not yet been approved for pre-chemo use and in fact has not yet reported Phase III
data in this setting, the increase for Xtandi in the pre-chemo setting was more dramatic on a
relative basis, from 0.7 to 1.9 patients per physician over the same period. In the post-chemo
setting, Zytiga use held steady (average of 3.0 patients per respondent at the end of both
December and March) and Xtandi use continued to increase from 1.8 to 2.6 patients per
respondent. Therefore, for both products, there was more growth, on an absolute basis, in the
pre-chemo setting as compared to post-chemo setting. For Zytiga, as of the end of December
2012, pre-chemo patients represented slightly less than half (46%) of the patients prescribed
Zytiga by our survey respondents and this increased to 62% at the end of March due to growth in
the pre-chemo patients. For Xtandi, the percentage of pre-chemo patients as a percent of total
Xtandi patients increased from 28% to 42% over the same period.
By physician specialty, increased pre-chemo use is predominantly driven by urologists.
Oncologists had 48% more patients on Zytiga in the pre-chemo setting in March than in
December. The increase in Xtandi is relatively modest from 0.9 patients on average to 1.3
patients on average. The increase for Zytiga was more pronounced but similar on a percentage
basis from 3.2 to 4.7 patients over the same period. Urologists use more Xtandi and Zytiga than
Mean Total Pre-chemo Post-chemo Total Pre-chemo Post-chemo Post-Zytiga Total Pre-chemo Post-chemo Total Pre-chemo Post-chemo Post-Zytiga
Total (n=50) 5.6 2.6 3.0 2.5 0.7 1.8 1.6 7.9 4.8 3.0 4.6 1.9 2.6 2.4
Oncologists (n=25) 6.7 3.2 3.6 3.8 0.9 2.9 2.6 8.0 4.7 3.3 5.2 1.3 3.9 3.6
Urologists (n=25) 4.4 2.0 2.4 1.3 0.5 0.8 0.6 7.8 5.0 2.8 4.0 2.6 1.4 1.1
% Increase Total Pre-chemo Post-chemo Total Pre-chemo Post-chemo Post-Zytiga
Total (n=50) 41% 88% 1% 80% 174% 43% 51%
Oncologists (n=25) 18% 48% -8% 36% 39% 35% 41%
Urologists (n=25) 76% 150% 15% 209% 433% 75% 100%
# on Zytiga
Dec-12 Mar-13
# on Zytiga# on Xtandi # on Xtandi
% Increase from Dec 2012 to Mar 2013
# on Zytiga # on Xtandi
Mean Pre-chemo Post-chemo Pre-chemo Post-chemo Post-Zytiga Pre-chemo Post-chemo Pre-chemo Post-chemo Post-Zytiga
Total (n=50) 46% 54% 28% 72% 61% 62% 38% 42% 58% 52%
Oncologists (n=25) 47% 53% 24% 76% 67% 59% 41% 25% 75% 70%
Urologists (n=25) 45% 55% 38% 63% 44% 64% 36% 65% 35% 28%
Dec-12 Mar-13
# on Zytiga # on Xtandi # on Xtandi# on Zytiga
1Q:13 vs. 4Q:12
growth rate
Zytiga (reported) 41%
Zytiga (survey: total) 41%
Zytiga (survey: oncologists) 18%
Zytiga (survey: urologists) 76%
Zytiga (IMS) 14%
4
BIOTECHNOLOGY May 6, 2013
oncologists in the pre-chemo setting. On average, urologists in the survey had 5 patients on
Zytiga and 2.6 patients on Xtandi in March of 2013, compared with 4.7 and 1.3 for oncologists.
Urologists drove increased use of Zytiga and Xtandi in the pre-chemo setting both on a relative
and absolute basis.
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
0.0
1.0
2.0
3.0
4.0
5.0
Dec 2012 Mar 2013
Mean number of patients
treated
Oncologists Usage of Zytiga and Xtandi in the Pre-Chemo Setting
Zytiga
Xtandi
+48%
+39%
0.0
1.0
2.0
3.0
4.0
5.0
6.0
Dec 2012 Mar 2013
Mean number of patients
treated
Urologists Usage of Zytiga and Xtandi in the Pre-Chemo Setting
Zytia
Xtandi
+150%
+433%
5
BIOTECHNOLOGY May 6, 2013
In aggregate, a little over half of Xtandi patients had previously received Zytiga, but this
differed significantly between oncologists and urologists. As of March 2013, approximately
52% of patients receiving Xtandi had previously received Zytiga and this declined somewhat from
61% three months prior in December 2012. There is a notable difference between specialties,
and post-Zytiga patients represented 70% of Xtandi patients for oncologists but only 28% for
urologists. We did not specifically ask whether post-Zytiga patients are also post-chemo, but
based on our conversations with MEDACorp physicians, we believe that there is some use of
Xtandi ahead of chemo in patients who progressed on Zytiga.
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
The overall number of patients on Zytiga and Xtandi is expected to be significantly higher
by the end of 2013. For Zytiga, a greater than 80% increase in patients is expected between
March 2013 and December 2013. For Xtandi, the increase is even more steep, a >150% increase
in patient numbers, albeit from a lower base. Thus the relative market share of Zytiga to Xtandi
across all of CRPC was 63%/37% in our survey as of March 2013, but is expected to be 54%/46%
by the end of 2013.
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Dec-12 Mar-13 Dec-12 Mar-13
Total (n=50) 72% 58% 61% 52%
Oncologists (n=25) 76% 75% 67% 70%
Urologists (n=25) 63% 35% 44% 28%
Post-Zytiga SettingPost-Chemo Setting
% of Xtandi Usage in the…
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
16.0
18.0
Dec-12 Mar-13 Dec-13 Dec-12 Mar-13 Dec-13
Zytiga Xtandi
# of Patients on Treatment
Mean Number of Patients on Zytiga and Xtandi
Total (n=50)
Oncologists (n=25)
Urologists (n=25)
6
BIOTECHNOLOGY May 6, 2013
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Most oncologists continue patients on Zytiga until progression; however, more urologists
are willing to continue treatment past progression. In our survey, oncologists indicated that
they treated with Zytiga until PSA or radiographic progression in most cases, with 16% willing to
treat post progression as long as it was well tolerated by the patient. Urologists were more willing
to continue treatment post progression, with 32% using this criteria, but 16% would stop treatment
upon a rise in PSA.
Survey Question: Please explain how you decide when to discontinue Zytiga treatment in the post-chemotherapy setting assuming tolerability is not limiting?
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Zytiga Xtandi
Total (n=50) 83.7% 166.7%
Oncologists (n=25) 94.0% 158.9%
Urologists (n=25) 73.2% 176.8%
% Increase in Projected Patients
from Mar to Dec 2013
Dec-12 Mar-13 Dec-13
Total (n=50) 31.4% 36.7% 45.7%
Oncologists (n=25) 36.1% 39.3% 46.4%
Urologists (n=25) 22.5% 33.8% 44.9%
Xtandi Market Share*
*Market share is defined as Xandi patients as a percentage of
patients on Xtandi and Zytiga.
Oncologists Urologists
Continue treatment post-progression as long as the patient can tolerate it 16% 32%
Treat to radiographic progression 36% 16%
Treat to PSA progression 48% 32%
Treat until PSA starts to rise 0% 16%
Other: both PSA progression and ragiographic progression (1x) 0% 4%
7
BIOTECHNOLOGY May 6, 2013
The practice of continuing Xtandi beyond progression appears relatively uncommon. Since
a substantial portion of current Xtandi use is in post-Zytiga patients, the duration of Xtandi could
be expected to be relatively short as current data suggest that both drugs are much less effective
in patients who had prior hormonal treatment such as ketoconazole. Anecdotally some physicians
have indicated that they continue the patient on drug post-progression, and we were interested in
how common this practice is. Based on our survey, treating beyond progression is relatively
uncommon among oncologists (8% in our survey) and appeared more common among urologists
but still represent less than a quarter of the surveyed urologists.
Survey Question: If you have used or plan to use Xtandi in patients who were previously treated with Zytiga, please explain how you decide when to discontinue Xtandi treatment in these patients assuming tolerability is not limiting.
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
The approval of Xtandi has an effect on the decision of when to stop treatment with Zytiga
for 30% of the physicians in the survey. Overall, 30% of physicians indicated that they had
changed their criteria on when to discontinue Zytiga treatment following the availability of Xtandi. It
is likely that at least in some cases patients are no longer continued on Zytiga post-progression
but switched to Xtandi instead. Most comments indicated that this was due to the availability of
another agent that could demonstrate additional efficacy or be better tolerated in certain patients.
Survey Question: Has the approval of Xtandi in the post-chemotherapy setting changed when you stop treatment with Zytiga in the post-chemotherapy setting?
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Oncologists Urologists
Continue treatment post-progression as long as the patient can tolerate it 8% 24%
Treat to PSA progression 48% 16%
Treat until PSA starts to rise 4% 24%
Treat to radiographic progression 36% 8%
I have not used or do not plan to use Xtandi in patients who were previously treated with Zytiga 4% 20%
Other: both symptomatic radiographic progression and PSA progression (x1), not sure (x1) 0% 8%
Yes No
Total survey respondents
(N=50)30% 70%
8
BIOTECHNOLOGY May 6, 2013
PHYSICIAN PERCEPTION ABOUT ZYTIGA AND XTANDI
More than 50% of respondents considered the efficacy and safety of Xtandi and Zytiga to
be similar in the post-chemotherapy setting, although it is possible that the difference
between oncologist and urologist perceptions may reflect the early stage of marketing
efforts for Xtandi. This result was true for both oncologists and urologists in our survey. Only 1
or 2 of the 50 respondents considered there to be a meaningful differences in safety or efficacy
between Xtandi and Zytiga. If we consider the difference in percentage of respondents that
believe that Zytiga is better than Xtandi, we see that the percentage of oncologists that consider
Zytiga to have better efficacy than Xtandi is approximately equal to the percentage that consider it
to have worse efficacy. However, on safety, we see that 36% of oncologists (9/26) believe that
Xtandi has better safety and tolerability than Zytiga, but only 4% (or 1 oncologist) believed the
inverse is true. In contrast, urologists consider the safety and tolerability of Xtandi to be similar to
Zytiga, but 28% consider Zytiga to have superior efficacy while only 8% consider Xtandi to be
more efficacious. As Xtandi is only approved for the post-chemo setting, MDVN and partner
Astellas have had limited presence in the urologist setting, therefore it is possible that the gap in
physician perception between the specialties may have been contributed to by the stage of
commercial promotion.
Survey Question: Please indicate your perception of the relative efficacy and safety / tolerability / convenience of Zytiga and Xtandi in the post-chemotherapy setting.
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Likely due to lack of Phase III data for Xtandi, urologists view the efficacy and safety of
Zytiga to be superior to Xtandi in the pre-chemo setting while oncologists consider Zytiga
to be better on efficacy but worse on safety/tolerability. In the pre-chemo setting, 12% of
oncologists and 16% of urologists were unable to respond to the question due to lack of data and
experience. Urologists experienced with both agents considered the safety and efficacy of Zytiga
Survey categories Efficacy
Safety,
tolerability and
convenience
Efficacy
Safety,
tolerability and
convenience
Zytiga meaningfully better than Xtanti 4.0% 0.0% 8.0% 8.0%
Zytiga modestly better than Xtandi 16.0% 4.0% 20.0% 16.0%
Zytiga and Xtandi are about the same 64.0% 60.0% 56.0% 52.0%
Xtandi modestly better than Zytiga 12.0% 28.0% 8.0% 16.0%
Xtandi meaningfully better than Zytiga 4.0% 8.0% 0.0% 4.0%
Unable to rate due to lack of data and experience 0.0% 0.0% 8.0% 4.0%
Regrouping of categories Efficacy
Safety,
tolerability and
convenience
Efficacy
Safety,
tolerability and
convenience
Zytiga better 20.0% 4.0% 28.0% 24.0%
Zytiga similar to Xtandi 64.0% 60.0% 56.0% 52.0%
Xtandi better 16.0% 36.0% 8.0% 20.0%
Unable to rate 0.0% 0.0% 8.0% 4.0%
% considering Zytiga better minus Xtandi better 4.00% -32.00% 20.00% 4.00%
Oncologists Urologists
Oncologists Urologists
Post-chemo
9
BIOTECHNOLOGY May 6, 2013
to be better than Xtandi, though 44% considered the two agents to be similar. While more
oncologists considered the efficacy of Zytiga to be superior to Xtandi, a higher percentage viewed
Xtandi to have the better safety and tolerability profile in the pre-chemo setting. We believe these
impressions of the relative profiles of these agents will likely change upon the release of the
Phase III PREVAIL results for Xtandi in the pre-chemo setting and once the Xtandi marketing
team can promote the agent for the pre-chemo setting.
Survey Question: Please indicate your perception of the relative efficacy and safety /
tolerability / convenience of Zytiga and Xtandi in the pre-chemotherapy setting.
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Survey categories Efficacy
Safety,
tolerability and
convenience
Efficacy
Safety,
tolerability and
convenience
Zytiga meaningfully better than Xtanti 16.0% 4.0% 8.0% 4.0%
Zytiga modestly better than Xtandi 28.0% 8.0% 28.0% 28.0%
Zytiga and Xtandi are about the same 20.0% 44.0% 44.0% 44.0%
Xtandi modestly better than Zytiga 20.0% 24.0% 4.0% 4.0%
Xtandi meaningfully better than Zytiga 4.0% 8.0% 0.0% 0.0%
Unable to rate due to lack of data and experience 12.0% 12.0% 16.0% 16.0%
Regrouping of categories Efficacy
Safety,
tolerability and
convenience
Efficacy
Safety,
tolerability and
convenience
Zytiga better 44.0% 12.0% 36.0% 32.0%
Zytiga similar to Xtandi 20.0% 44.0% 44.0% 44.0%
Xtandi better 24.0% 32.0% 4.0% 4.0%
Unable to rate 12.0% 12.0% 16.0% 16.0%
% considering Zytiga better minus Xtandi better 20.00% -20.00% 32.00% 28.00%
Pre-chemoOncologists Urologists
Oncologists Urologists
10
BIOTECHNOLOGY May 6, 2013
Lack of statistically significant OS benefit for Xtandi in PREVAIL is projected to lead to a
less than 10% decline in market share over the scenario with only an OS trend, although
this would correspond to a 20%+ loss on a relative basis. One year after presumed Xtandi
approval in the pre-chemo setting, assuming PREVAIL shows a statistically significant overall
survival benefit, Xtandi is projected to overtake Zytiga with a 43% market share as the first-line
treatment for metastatic prostate cancer compared to 34% for Zytiga. If Xtandi shows a non-
statistically significant overall survival trend, these market share projections would reverse (34%
for Xtandi vs. 44% for Zytiga). We believe this reflects physicians’ impressions that Zytiga does
confer an OS benefit and that the agents are similar in efficacy and safety/tolerability in the post-
chemotherapy setting.
Chemotherapy will still be appropriate for a minority of patients even with the new oral
agents. Chemotherapy will continue to hold market share in the 1st line metastatic CRPC with
~23% of patients expected to receive these agents. A MEDACorp key opinion leader explained
that for some patients with visceral metastases or aggressive tumor -- about 20% of the patients in
this setting by his estimate -- it is appropriate to give chemotherapy first to attempt to control the
disease before giving a hormonal agent.
Generic Zytiga is projected to have a negative impact on Xtandi, but it appears to take more
share from chemotherapy. Xtandi will lose market share once Zytiga is generic; however, there
will still be substantial usage of Xtandi in 28% of the patients in our survey. With generic Zytiga,
chemotherapy usage in frontline metastatic CRPC expected to fall from 23% to 14%. This would
appear to indicate that the high cost of the oral hormonal agents may be another reason why
chemotherapy is used as the first agent in metastatic prostate cancer patients.
Survey Question: If both Zytiga and Provenge are approved in the pre-chemotherapy/1st
line metastatic setting, how do you see your market share usage of the two agents in this
setting?
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
One year after Xtandi pre-chemo
approval, if Xtandi demonstrates
statistically significant OS
One year after Xtandi pre-
chemo approval, if Xtandi
demonstrates non-statistically
significant OS
Once Zytiga is generic
Oncologists
Zytiga 1st line market share 35% 46% 53%
Xtandi 1st line market share 44% 36% 30%
Chemo 1st line market share 21% 18% 17%
Urologists
Zytiga 1st line market share 34% 41% 63%
Xtandi 1st line market share 42% 31% 27%
Chemo 1st line market share 25% 28% 10%
11
BIOTECHNOLOGY May 6, 2013
The vast majority of physicians across both medical specialties would prefer to use the
other hormonal agent first prior to chemotherapy after progression on 1st
line therapy.
Many physicians cited the better tolerability of Xtandi and Zytiga over chemotherapy as their
reason for sequencing the two agents prior to cytotoxic therapy.
Survey Question: Do you anticipate using the alternate agent (Zytiga or Xtandi) once a
patient progresses on 1st
line therapy? Or would you prefer to use chemotherapy upon
progression?
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
SEIZURE CASES ON XTANDI
More oncologists than urologists have prescribed Xtandi. For the 25 oncologists in our
survey, only 8% (2/25) had not yet prescribed Xtandi, and one of those was looking to prescribe
the agent to the appropriate patient. On the urology side, more than half of the survey
respondents (13/25) had no clinical experience with Xtandi. Reasons for not having prescribed
Xtandi spanned a range of responses, but reimbursement and not yet identifying an appropriate
patient were common.
Survey Question: Have you prescribed Xtandi? No, please explain.
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Yes, use alternative agent if patient progresses No, use chemotherapy upon progression
Oncologists (n=25) 76% 24%
Urologists (n=25) 76% 24%
Oncologists Urologists
Yes 92% 48%
No 8% 52%
Reasons for not prescribing Xtandi No clinical situation yet for use No candidates identified yet
Too expensive Reimbursement issues
I am not comfortable.
not covered with insurance
Have not had approved yet
Have preferred Zytiga
I have one patient currently on Xtandi that was
prescribed by Medical Oncologist
patient's can not afford post chemo Xtandi
not yet
not yet availab le on formulary
Oncology shared patient
plan to
plan to in future
12
BIOTECHNOLOGY May 6, 2013
For physicians prescribing Xtandi, urologists and oncologists had similar numbers of
patients on drug. Of the 35 respondents who had prescribed Xtandi, on average they had
prescribed the drug to 7-8 patients and the results were similar for oncologists and urologists. In
total, there were 265 patients prescribed Xtandi under the care of physicians in our survey.
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
There were a total of 4 patients with seizures in our survey. Two physicians had each seen
two patient seizures after prescribing Xtandi. Both physicians indicated that these seizures had
changed their willingness to prescribe Xtandi. We note that 4 seizures in 265 total Xtandi patients
yield a 1.5% incidence rate, similar to the 0.9% rate listed in the FDA label.
PROVENGE UTILIZATION TRENDS Survey respondents report declining use of Provenge since December 2012. We inquired
about Provenge usage for the respondents. On average, each physician only treated 1-2 patients
per month, thus we aggregated the number of patients by specialty. We see that the number of
patients treated per month declined in January and February by 16% in each month compared to
the previous month, but stabilized in March (1% decline month-over-month) for both urologists and
oncologists. The average monthly number of patients treated with Provenge in 1Q:13 declined by
25% compared to December 2012, and the number of patients receiving Provenge in the last
month of 1Q:13 (March) vs. 4Q:12 (December) declined by 30%. On an individual doctor basis,
18% of the survey respondents reported an increase in the average monthly Provenge volume in
1Q:13 vs. December 2012, 22% reported no change, but the majority (60%) reported a decline.
This distribution is essentially identical for urologists and oncologists, therefore our survey did not
detect a gain of Provenge among urologists during 1Q. Potential contributors to the Provenge
volume decline may include the effect of Medicare and private insurance co-pay resetting at the
beginning of the year, and Zytiga pre-chemo approval in December and the Xtandi launch in
September and compendium listing in December. While it is difficult to tease out the contribution
of each, continued decline from January to February leads us to believe that the decline is not only
due to reimbursement resetting, and increased use of oral hormonal agents had an impact.
Mean Median Total
Oncologists (n=23) 7.7 5.0 178
Urologists (n=12) 7.3 5.0 87
Total (n=35) 7.6 5.0 265
Xtandi Patients
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BIOTECHNOLOGY May 6, 2013
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
However, Provenge usage is projected to rebound, with a robust 73% growth in patient
numbers for 4Q:13 compared with 1Q:13. Below we see a table with the monthly usage of
Provenge from December 2012 to March 2013 as well as the projected usage in 4Q:13. Across
both urologists and oncologists, there is a marked increase expected in Provenge usage. The
vast majority of urologists in our survey (76%) expect to increase Provenge prescribing in 4Q:13
compared with 1Q:13. Similarly, 56% of oncologists expected an increase in prescribing. Only
8% of respondents in both specialties expected to decrease their Provenge prescribing. Relative
to Dec. 2012 levels, total number of patients on Provenge in our survey sample is projected to
increase by 34% in Dec. 2013, and this is relatively consistent between urologists and oncologists.
On an individual prescriber basis, we see that there is a wide range of Provenge usage. A few
physicians are projecting very high usage in December 2013, while many physicians are
projecting no usage of Provenge at the end of December 2013.
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
0
20
40
60
80
100
120
Dec-12 Jan-13 Feb-13 Mar-13
Total Number of Provenge Patients
Treated
Dec-12 Jan-13 Feb-13 Mar-13
Total 112 94 79 78
Oncologists (n=25) 58 49 43 44
Urologists (n=25) 54 45 36 34
Total Number of Provenge Treatments by Specialty
Dec-12 Jan-13 Feb-13 Mar-13 Oct-13 Nov-13 Dec-13
# of Provenge Patients
Total 112 94 79 78 142 142 150
Oncologists (n=25) 58 49 43 44 75 75 80
Urologists (n=25) 54 45 36 34 67 67 70
% change Dec 12 to Dec 13
Total (n=50) 34%
Oncologists (n=25) 38%
Urologists (n=25) 30%
% change for 1Q:13 to 4Q:13
Total (n=50) 73%
Oncologists (n=25) 69%
Urologists (n=25) 77%
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BIOTECHNOLOGY May 6, 2013
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
From the change in projected Provenge usage by current use in Provenge, we see that the
increase in usage is across a wide spectrum of prescribing physicians. Some physicians
who are not prescribing Provenge currently intend to start prescribing the agent. Of the 27
physicians who had not prescribed Provenge in March 2013, 15 expected to prescribe the agent in
December 2013. Furthermore, the most active users also intend to increase their prescribing.
Only a couple of the current users expected their prescribing to decrease by year-end 2013. We
do not fully understand the reason for the projected increased use of Provenge by the end of
2013, considering that Provenge has been approved for 3 years and its sales trajectory has been
relatively flat.
Increase No Change Decrease
Total 66% 26% 8%
Oncologists 56% 36% 8%
Urologists 76% 16% 8%
% of Respondents by Expected Change in
Provenge Prescribing from 1Q to 4Q 2013
0
5
10
15
20
25
30
# of Provenge Patients
Reported Provenge Pateints in Dec 2012
Oncologists Urologists
0
5
10
15
20
25
30
# of Provenge Patients
Projected Provenge Pateints in Dec 2013
Oncologists Urologists
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BIOTECHNOLOGY May 6, 2013
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Although many respondents indicated declining usage of Provenge after Zytiga pre-chemo
approval and Xtandi post-chemo approval, this appears to mainly affect the casual users
and to have limited impact on existing heavy users. When we examine the users of Provenge
(who had prescribe the agent to at least 1 patient during March 2013), we see that the highest
prescribers expect no effect from the recent label expansion of Zytiga or the Xtandi approval.
However, users who only infuse 1 patient a month are more likely to decrease their usage of
Provenge due to the availability of new agents.
-2
0
2
4
6
8
10
12
0 2 4 6 8 10 12 14 16 18
Projected Change in Provenge Patients in December 2013
# of Provenge Patients Treated in March 2013
Change in Expected Number of Provenge Patients by Current Patients Treated
Change in Number of Patients
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BIOTECHNOLOGY May 6, 2013
Survey Question: How has your usage of Provenge changed with the Zytiga pre-chemo
approval and the Xtandi post-chemo approval?
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
Despite Xtandi’s lack of prednisone co-administration, physicians do not consider its
approval as a positive for Provenge usage. However, for the vast majority of prescribers, they
expect no change in usage from the approval of Xtandi in the pre-chemo setting. A few
prescribers do expect less usage of Provenge due to another agent being available, while only a
couple of physicians expect to increase usage of Provenge due to the lack co-administration of
prednisone with Xtandi.
# Provenge Pts -
March 2013Comments Usage Change Specialty
16 it has not changed significantly so far. No change Oncologist
14 It has stayed relatively the same. No change Urologist
6 I have used it less because of more options. Less Oncologist
5 no. No change Oncologist
5 use of provenge has remained constant since more men
being treated with one of three therapies, where in past
chemotherapy was only option
No change Urologist
4 not much as i still use provenge No change Oncologist
3 No fifteenth rationale No change Oncologist
3 No. It remains foundational therapy No change Urologist
3 It hasn't. No change Urologist
3 less provenge use. provenge is labor intensive to utilizeNo change Urologist
2 PROVENGE WILL BE USED IN BIOCHEMICAL FAILURE WITH CASTRATE RESISTANTNo change Oncologist
2 no, will still use provenge first No change Oncologist
2 No i use provenge first No change Urologist
1 slightly less use as Zytiga easier to arrange Less Oncologist
1 have had problems with steroid use with abiraterone Less Oncologist
1 I reduced the use of Provenge Less Oncologist
1 Decreased use of provenge Less Oncologist
1 No change, the indications are separate No change Oncologist
1 no change No change Oncologist
1 decrease use of provenge since zytiga is oral Less Urologist
1 I will not go up due to cost of Zytiga Less Urologist
1 n/a No change Urologist
1 Diminished. Much less complicated with Zytiga Less Urologist
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BIOTECHNOLOGY May 6, 2013
Survey Question: Will your usage of Provenge change as a result of the approval of Xtandi
in pre-chemo patients (which does not require co-administration of prednisone)? Please
explain:
Source: MEDACorp survey, “Treatment of Prostate Cancer”, April 2013
MEDACorp performed this survey on behalf of a Leerink Swann LLC analyst. The analyst in
conjunction with MEDACorp developed the questions contained in the survey.
4
# Provenge Pts -
March 2013Comments Usage Change Specialty
16 It has not changed so far. No Oncologist
14 It may. I will have to wait for more data before changing usage of
provengeUnclear Urologist
6 Yes, similar to reason above. Less Oncologist
5 no No Oncologist
5 use of provenge to remain same as more men now being treated
for CRPC. not needing prednisone is nice but not significant
enought to influence therapies.
No Urologist
4 no No Oncologist
3 No will not No Oncologist
3 No. It remains foundational therapy No Urologist
3 It will not. No Urologist
3 less provenge use for same reasons above Less Urologist
2 NO. I AM USING PROVENGE ONLY IN A ELECTED GROUP OF
PATIENTSNo Oncologist
2 no, will still use provenge first in all appropriate pts No Oncologist
2 Yes more use if no prednisone Increase Urologist
1 not sure but possib ly Unclear Oncologist
1 will use with xtandi No Oncologist
1 It is already minimal. If the patient requests Provenge it will be fine.No Oncologist
1 Decreased use of Provenge Less Oncologist
1 No change, the indications are separate No Oncologist
1 no change No Oncologist
1 same No Urologist
1 No. Prefer Zytiga No Urologist
1 yes better tolerance Increase Urologist
1 Yes. Provenge is more complicated to my practice routine. Less Urologist
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BIOTECHNOLOGY May 6, 2013
TREATMENT OF PROSTATE CANCER
Respondent Distribution
Geographic Distribution
Source: Google Maps
Specialty Oncology and Urology
Trend Prostate Cancer
Number of Respondents 25 Oncologists and 25 Urologists
Respondent Distribution United States
Survey Date April 2013
Responses represent an average of the aggregate responses (n=50) unless otherwise noted. Inclusion Criteria Screener 1: How many metastatic castration-resistant prostate cancer patients have you personally managed over the past 12
months?
Mean Median Sum
Number of metastatic castration-resistant prostate cancer patients I personally managed over the past 12 months
82.4 50 4,121
Screener 2: What is your medical specialty?
50.0% Oncologists
50.0% Urologists
0.0% Other
Survey Questions
1. Which best describes your primary practice setting?
28.0% Academic medical center
12.0% Community hospital
2.0% VA hospital
54.0% Private practice
4.0% Clinic
0.0% Other
2. How many prostate cancer patients do you personally manage currently? Of these, how many are castration-resistant prostate
cancer (CRPC) patients?
Mean Median Sum
Total number of prostate cancer patients that you personally manage 247.9 155 12,396
Castration-resistant prostate cancer (CRPC) 56.1 42 2,804
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BIOTECHNOLOGY May 6, 2013
How many of your castration-resistant prostate cancer (CRPC) patients are in the following categories?
Mean Median Sum
Metastatic castration-resistant prostate cancer (mCRPC) before receiving chemotherapy
27.7 21 1,384
mCRPC currently receiving first-line chemotherapy 14.6 10 729
mCRPC after first-line chemotherapy 13.5 10 676
How many of the patients you personally managed were treated with Provenge during the following time periods?
Mean Median Sum
December 2012 2.2 1 112
January 2013 1.9 1 94
February 2013 1.6 1 79
March 2013 1.6 0 78
How many of the patients you personally managed were treated with Zytiga and Xtandi at the end of December 2012 and at the end of March 2013, respectively?
At the end of December 2012
Mean Median Sum
Number of patients receiving Zytiga 5.6 4 278
Of patients receiving Zytiga, how many patients had already received chemotherapy?
3.0 2 149
Number of patients receiving Xtandi 2.5 1 127
Of patients receiving Xtandi, how many patients had already received chemotherapy?
1.8 1 92
Of patients receiving Xtandi, how many patients had already received Zytiga?
1.6 1 78
At the end of March 2013
Mean Median Sum
Number of patients receiving Zytiga 7.9 5 393
Of patients receiving Zytiga, how many patients had already received chemotherapy?
3.0 3 151
Number of patients receiving Xtandi 4.6 2 228
Of patients receiving Xtandi, how many patients had already received chemotherapy?
2.6 2 132
Of patients receiving Xtandi, how many patients had already received Zytiga?
2.4 2 118
Please project the number of patients on Provenge during the following time periods:
Mean Median Sum
October 2013 2.8 2 142
November 2013 2.8 2 142
December 2013 3.0 2 150
Please project the number of patients on Zytiga and Xtandi at the end of 2013.
Mean Median Sum
Number of patients receiving Zytiga 14.4 10 722
Number of patients receiving Xtandi 12.2 9 608
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BIOTECHNOLOGY May 6, 2013
3. Please explain how you decide when to discontinue Zytiga treatment in the post-chemotherapy setting assuming tolerability is not limiting?
26.0% Treat to radiographic progression
40.0% Treat to PSA progression
8.0% Treat until PSA starts to rise
24.0% Continue treatment post-progression as long as the patient can tolerate it
0.0% I have not used or do not plan to use Xtandi in patients who were previously treated with Zytiga
2.0% Other: both PSA progression and radiographic progression (1x)
4. Has the approval of Xtandi in the post-chemotherapy setting changed when you stop treatment with Zytiga in the post-
chemotherapy setting?
30.0% Yes
70.0% No
Please explain. See Appendix for a summary of responses
5. If you have used or plan to use Xtandi in patients who were previously treated with Zytiga, please explain how you decide when to discontinue Xtandi treatment in these patients assuming tolerability is not limiting.
22.0% Treat to radiographic progression
32.0% Treat to PSA progression
14.0% Treat until PSA starts to rise
16.0% Continue treatment post-progression as long as the patient can tolerate it
12.0% I have not used or do not plan to use Xtandi in patients who were previously treated with Zytiga
4.0% Other: both symptomatic radiographic progression and PSA progression (1x)
6. Please indicate your perception of the relative efficacy and safety / tolerability / convenience of Zytiga and Xtandi in the post-
chemotherapy setting.
Efficacy Safety, tolerability and convenience
Zytiga meaningfully better than Xtanti 6.0% 4.0%
Zytiga modestly better than Xtandi 18.0% 10.0%
Zytiga and Xtandi are about the same 60.0% 56.0%
Xtandi modestly better than Zytiga 10.0% 22.0%
Xtandi meaningfully better than Zytiga 2.0% 6.0%
Unable to rate due to lack of data and experience 4.0% 2.0%
Please indicate your perception of the relative efficacy and safety / tolerability / convenience of Zytiga and Xtandi in the pre-chemotherapy setting.
Efficacy Safety, tolerability and convenience
Zytiga meaningfully better than Xtanti 12.0% 4.0%
Zytiga modestly better than Xtandi 28.0% 14.0%
Zytiga and Xtandi are about the same 32.0% 42.0%
Xtandi modestly better than Zytiga 12.0% 18.0%
Xtandi meaningfully better than Zytiga 2.0% 8.0%
Unable to rate due to lack of data and experience 14.0% 14.0%
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BIOTECHNOLOGY May 6, 2013
7. Have you prescribed Xtandi?
70.0% Yes
30.0% No: See Appendix
How many patients have you prescribed Xtandi to in any setting? (n=35)
Mean Median Sum
Number of patients to whom you’ve personally prescribed Xtandi to in any setting 7.6 5 265
Have you seen a case of seizure in patients receiving Xtandi? (n=35)
5.7% Yes
94.3% No
How many patients have had seizures after receiving Xtandi? (n=2)
Mean Median Sum
Number of patients who have had seizures while receiving Xtandi 2.0 2 4
Has this experience changed your willingness to prescribe Xtandi? (n=2)
100.0% Yes
0.0% No
8. If both Zytiga and Provenge are approved in the pre-chemotherapy/1st line metastatic setting, how do you see your market
share usage of the two agents in this setting?
One year after Xtandi pre-chemo approval, if Xtandi demonstrates statistically significant OS
One year after Xtandi pre-chemo approval if Xtandi demonstrates non-statistically significant OS trend
Once Zytiga is generic
Zytiga 1st line market share 34.2% 43.7% 58.0%
Xtandi 1st line market share 42.8% 33.5% 28.1%
Chemotherapy 23.0% 22.8% 13.9%
9. Do you anticipate using the alternate agent (Zytiga or Xtandi) once a patient progresses on 1
st line therapy? Or would you
prefer to use chemotherapy upon progression?
76.0% Yes, prefer to use alternate agent if patient progresses on 1st line therapy
24.0% No, prefer to use chemotherapy upon progression
Please explain: See Appendix for a summary of responses
10. How has your usage of Provenge changed with the Zytiga pre-chemo approval and the Xtandi post-chemo approval? Please explain: See Appendix for a summary of responses
11. Will your usage of Provenge change as a result of the approval of Xtandi in pre-chemo patients (which does not require co-
administration of prednisone)? Please explain: See Appendix for a summary of responses
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BIOTECHNOLOGY May 6, 2013
Appendix: Summary of responses. Question 4: Has the approval of Xtandi in the post-chemotherapy setting changed when you stop treatment with Zytiga in the post-
chemotherapy setting? Please explain.
1 No, PFS benefits seen with both.
2 Generally go to Xtandi prior to Jevtana
3 Still have chemotherapy in between prior to using Xtandi
4 Use Zytiga until response ends and then move to Xtandi
5 I still treat till clinical or radiographic progression
7 I use Xtandi after Zytiga
8 Approval of Xtandi is for chemotherapy failures so use or no[ne] use of Zytiga should not be an issue
9 Has influenced no change
10 No impact of one over the other
11 I generally do not stop Zytiga for Xtandi
12 I use Zytiga until it is no longer clinically helpful for the patient.
13 Xtandi after Zytiga
14 No. PSA doubling in 3 months or less would be a clear indication for change. Otherwise 2 consecutive progressions 3 months apart.
15 Decrease its use in favor of Xtandi
16 Use less
17 I have been using Zytiga in pre chemo setting
19 My pattern of treatment remains the same due to expense of Xtandi
20 Still treat to PSA progression
21 One more agent available to treat patients after they fail Zytiga
22 Still treat to progression or toxicity
23 I have more Zytiga experience
24 Additional option now available.
25 Will still treat to PSA progression
26 I switch to Xtandi on PSA progression
27 Don’t think that will make a difference. I imagine both will be approved pre and/or post chemo.
28 Has not changed current practice
29 No, I continue to use Zytiga in the post chemotherapy setting despite the approval of Xtandi. I am using more Zytiga in pre-chemotherapy setting however.
30 Proceeding with recommendations from medical oncology here
31 Has not changed as far as I am aware.
32 I still use Zytiga as first line Rx
33 Have not used Xtandi yet
34 Quicker to switch
35 It has had no impact
36 Would be more apt to switch from Zytiga to Xtandi after PSA progression
37 Yes. We have had some responders that have failed or progressed on Zytiga
38 No effect
39 Difficult for patient to afford out of pocket Xtandi, Xtandi is more expensive than Zytiga
40 Easier use of this class of med. Adrenal sparing
41 Not sure about latest change
42 I would still use.
43 No clear superiority of one agent over the other
44 Can continue Zytiga
46 No bearing on when to stop Zytiga
47 Adverse reaction
48 About to start using Xtandi. No experience thus far
49 Zytiga end-point is determined by clinical response
50 Cost prohibitive to patient
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BIOTECHNOLOGY May 6, 2013
Question 7: Have you prescribed Xtandi? No, please explain
8 No clinical situation yet for use
23 Too expensive
28 No candidates identified yet
30 Reimbursement issues
31 I am not comfortable.
32 Not covered with insurance
33 Have not had approved yet
35 Have preferred Zytiga
36 I have one patient currently on Xtandi that was prescribed by Medical Oncologist
39 Patients cannot afford post chemo Xtandi
41 Not yet
43 Not yet available on formulary
44 Oncology shared patient
45 Plan to
48 Plan to in future
Question 9: Do you anticipate using the alternate agent (Zytiga or Xtandi) once a patient progresses on 1
st line therapy? Or
would you prefer to use chemotherapy upon progression?
1 I would switch back to cytotoxic chemotherapy.
2 Depends on many circumstances however to include pace of disease
3 Different mechanism of action
4 To avoid chemotherapy
5 As most patients don’t want chemo.
6 Especially for visceral disease
7 It will be up to the patient to decide
8 They work by different mechanisms so patients will ultimately see both drugs most of the time
9 Seems like it would be better tolerated
10 Would like to maximize hormonal tx just like in breast cancer, prior to starting chemo
11 Both Zytiga and Xtandi has shown efficacy
12 Prefer oral medications whenever possible.
13 Patients prefer pills to chemo
14 I considered and still consider to use either Zytiga or Xtandi. We (oncologists) in this case I always use another hormonal agent after first line hormonal failure
15 Would need data showing that one can do it.
16 Don’t think it’s different
17 I prefer to keep chemo last.
18 Toxicity issue
19 If a patient has no response or short response to Zytiga or Xtandi , I would want a proven survival benefit with chemotherapy to give to appropriate patients
20 It depends on rapidity or aggressiveness of disease
21 Options available come handy to treat
22 Want to delay chemo as long as possible
23 It depends on PS
24 Other chemotherapy has demonstrated some efficacy on progressed tumors. The alternate agent can be considered in the future with additional trial results proving their superior efficacy.
25 Better side effect profile
26 More tolerable
27 Would be able to manage patients myself this way as opposed to referral to Med Onc.
28 No data yet to help guide this situation - unable to answer
29 If patients fail Zytiga or Xtandi, they will have better disease free survival if they are started on chemotherapy
30 Might not need oncology right away
31 Too many medications with toxicity, I don't want to use it unless approved and am comfortable with.
32 I may add hi dose ketoconazole, avodart and consider chemotherapy
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BIOTECHNOLOGY May 6, 2013
33 Better other before chemo
34 Less toxicity
35 Have seen benefits from chemo
36 I believe these oral agents are preferable to chemo from convenience and toxicity standpoint. Cost remains a significant concern.
37 In conjunction with med onc, would prefer to delay chemo rx as long as possible
38 Less side effects
39 Will use Zytiga, more affordable, better reduction in PSA
40 Yes I believe hormonal manipulation early handsome benefits
41 I understand that some of these agents are/were not approved before first line chemo in prostate cancer patients. I like to use these agents wherever the indications are.
42 Chemo better.
43 Less toxic side effects and better tolerability and compliance
44 NCCN guidelines before change
45 Consider other options
46 Limit chemotherapy toxicity, ease of administration
47 Depends on the patient, a shift to chemotherapy happens very rarely (less than 1%) but can happen. Otherwise, would rather the alternate agent.
48 Zytiga is much well tolerated than chemo and easier to administer
49 Less toxic. Treatment in my hands, rather than oncologist
50 Continue to monitor the patient.
Question 10: How has your usage of Provenge changed with the Zytiga pre-chemo approval and the Xtandi post-chemo
approval?
1 I have used it less because of more options.
2 Slightly less use as Zytiga easier to arrange
3 Have had problems with steroid use with abiraterone
4 Using it less
5 Not much as I still use Provenge
6 About the same
7 I reduced the use of Provenge
8 Still use Provenge for minimally symptomatic patients
9 No
10 Decreased use of Provenge
11 It has not changed significantly so far.
12 It has not changed, since I do not use it.
13 Don’t use Provenge
14 No change
15 Much deceased
16 No real rationale, just practice patterns.
17 I have been using less and less of Provenge with Zytiga approval. I do use it in biochemical failure prostate cancer with minimal bone disease or no appreciable metastatic disease in selected group of patients.
18 None
19 No change, the indications are separate
20 No change
21 Decreased
22 No, will still use Provenge first
23 Didn't change
24 No.
25 Don't use Provenge.
26 Less
27 Provenge use down.
28 No change - I believe Provenge should be used in many patients before Xtandi and Zytiga
29 Use of Provenge has remained constant since more men being treated with one of three therapies, where in past chemotherapy was only option
30 No
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BIOTECHNOLOGY May 6, 2013
31 I have not used Provenge yet.
32 Decrease use of Provenge since Zytiga is oral
33 No I use Provenge first
34 No. It remains foundational therapy
35 I will not go up due to cost of Zytiga
36 I don't use much Provenge although our cancer center is a recently approved site. Our patients still have to travel a considerable distance for the apheresis. I believe it still has a role in managing CRPC but will probably use more now for those patients who have failed Zytiga/Xtandi and prior to chemo.
37 Decreased
38 Stopped
39 Yes, use Provenge first, and then Zytiga, only Xtandi if patient can pay out of pocket
40 Not much do not believe in usefulness
41 Yes
42 It hasn't.
43 Decrease use of Provenge
44 Earlier use of Zytiga
45 Decrease
46 No change. Do not use
48 Less Provenge use. Provenge is labor intensive to utilize
49 Diminished. Much less complicated with Zytiga
50 It has stayed relatively the same.
19 I have used it less because of more options.
20 Slightly less use as Zytiga easier to arrange
21 Have had problems with steroid use with abiraterone
22 Using it less
23 Not much as I still use Provenge
24 About the same
25 I reduced the use of Provenge
26 Still use Provenge for minimally symptomatic patients
Question 11: Will your usage of Provenge change as a result of the approval of Xtandi in pre-chemo patients (which does not
require co-administration of prednisone)? Please explain:
1 Yes, similar to reason above.
2 Not sure but possibly
3 Will use with Xtandi
4 Will increase AFTER maximal endocrine therapy
5 No
6 No
7 It is already minimal. If the patient requests Provenge it will be fine.
8 No will use in low symptom patient
9 No
10 Decreased use of Provenge
11 It has not changed so far.
12 No.
13 Don’t use Provenge
14 No change
15 Yes, decrease
16 No will not
17 No. I am using Provenge only in a selected group of patients
18 Less use
19 No change, the indications are separate
20 No change
21 Yes, decreased further
22 No, will still use Provenge first in all appropriate patients
23 No
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BIOTECHNOLOGY May 6, 2013
24 No
25 No
26 Moderately.
27 Probably remain the same. Zytiga already approved pre chemo.
28 No change - I believe Provenge should be used in many patients before Xtandi and Zytiga
29 Use of Provenge to remain same as more men now being treated for CRPC. Not needing prednisone is nice but not significant enough to influence therapies.
30 Possibly less
31 I haven’t used Provenge yet
32 Same
33 Yes more use if bo prednisone
34 No. It remains foundational therapy
35 No. Prefer Zytiga
36 See above answer. Will use Xtandi more after developing castrate resistance, especially since don't need prednisone, prior to using Provenge or chemo. Would also delay referral to Med Onc if using Xtandi first.
37 Yes it will decrease because these pts have better performance status earlier in the disease stage and they would have been candidate for Provenge but will now likely try Xtandi first
38 Limit it
39 Yes, will use Xtandi, definitely a benefit not to have to use prednisone
40 No still not using it much
41 It will go down
42 It will not.
43 May decrease
44 No
45 Yes
46 No. Do not use
47 Yes better tolerance
48 Less Provenge use for same reasons above
49 Yes. Provenge is more complicated to my practice routine.
50 It may. I will have to wait for more data before changing usage of Provenge
19 Yes, similar to reason above.
20 Not sure but possibly
21 Will use with Xtandi
22 Will increase AFTER maximal endocrine therapy
23 No
24 No
25 It is already minimal. If the patient requests Provenge it will be fine.
26 No will use in low symptom patient
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BIOTECHNOLOGY May 6, 2013
BIOTECHNOLOGY May 6, 2013
Disclosures AppendixAnalyst CertificationI, Howard Liang, Ph.D., certify that the views expressed in this report accurately reflect my views and that no part ofmy compensation was, is, or will be directly related to the specific recommendation or views contained in this report.
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BIOTECHNOLOGY May 6, 2013
Distribution of Ratings/Investment Banking Services (IB) as of 03/31/13IB Serv./Past 12
Mos.Rating Count Percent Count PercentBUY [OP] 107 61.14 32 29.91HOLD [MP] 68 38.86 0 0.00SELL [UP] 0 0.00 0 0.00
Explanation of RatingsOutperform (Buy): We expect this stock to outperform its benchmark over the next 12 months.
Market Perform (Hold/Neutral): We expect this stock to perform in line with its benchmark over the next 12months.
Underperform (Sell): We expect this stock to underperform its benchmark over the next 12 months.The degreeof outperformance or underperformance required to warrant an Outperform or an Underperform rating shouldbe commensurate with the risk profile of the company.
For the purposes of these definitions the relevant benchmark will be the S&P 600® Health Care Index forissuers with a market capitalization of less than $2 billion and the S&P 500® Health Care Index for issuers witha market capitalization over $2 billion.
From October 1, 2006 through January 8, 2009, the relevant benchmarks for the above definitions were theRussell 2000® Health Care Index for issuers with a market capitalization of less than $2 billion and the S&P500® Health Care Index for issuers with a market capitalization over $2 billion.
Definitions of Leerink Swann Ratings prior to October 1, 2006 are shown below:
Outperform (Buy): We expect this stock to outperform its benchmark by more than 10 percentage points overthe next 12 months.
Market Perform (Hold/Neutral): We expect this stock to perform within a range of plus or minus 10 percentagepoints of its benchmark over the next 12 months.
Underperform (Sell): We expect this stock to underperform its benchmark by more than 10 percentage pointsover the next 12 months.
For the purposes of these definitions, the relevant benchmark were the Russell 2000® Health Care Index forissuers with a market capitalization of less than $2 billion and the S&P 500® Index for issuers with a marketcapitalization over $2 billion.
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BIOTECHNOLOGY May 6, 2013
Important DisclosuresThis information (including, but not limited to, prices, quotes and statistics) has been obtained from sourcesthat we believe reliable, but we do not represent that it is accurate or complete and it should not be relied uponas such. All information is subject to change without notice. This is provided for information purposes onlyand should not be regarded as an offer to sell or as a solicitation of an offer to buy any product to which thisinformation relates. The Firm, its officers, directors, employees, proprietary accounts and affiliates may have aposition, long or short, in the securities referred to in this report, and/or other related securities, and from timeto time may increase or decrease the position or express a view that is contrary to that contained in this report.The Firm's salespeople, traders and other professionals may provide oral or written market commentary ortrading strategies that are contrary to opinions expressed in this report. The Firm's asset management groupand proprietary accounts may make investment decisions that are inconsistent with the opinions expressed inthis report. The past performance of securities does not guarantee or predict future performance. Transactionstrategies described herein may not be suitable for all investors. Additional information is available uponrequest by contacting the Publishing Department at One Federal Street, 37th Floor, Boston, MA 02110.
Like all Firm employees, analysts receive compensation that is impacted by, among other factors, overallfirm profitability, which includes revenues from, among other business units, the Private Client Division,Institutional Equities, and Investment Banking. Analysts, however, are not compensated for a specificinvestment banking services transaction.
Leerink Swann Consulting LLC, an affiliate of Leerink Swann LLC, is a provider of evidence-based strategyand consulting to the healthcare industry.Leerink Swann LLC makes a market in Dendreon Corporation and Medivation, Inc.Leerink Swann LLC is willing to sell to, or buy from, clients the common stock of Johnson & Johnson on aprincipal basis.In the past 12 months, an affiliate of the Firm, Leerink Swann Consulting LLC, has received compensation forproviding non-securities services to: Johnson & Johnson.
©2013 Leerink Swann LLC. All rights reserved. This document may not be reproduced or circulated withoutour written authority.
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Leerink Swann LLC Equity Research
Director of Equity Research John L. Sullivan, CFA (617) 918-4875 [email protected]
Associate Director of Research Alice C. Avanian, CFA (617) 918-4544 [email protected] Healthcare Strategy John L. Sullivan, CFA (617) 918-4875 [email protected]
Alice C. Avanian, CFA (617) 918-4544 [email protected]
Biotechnology Howard Liang, Ph.D. (617) 918-4857 [email protected]
Joseph P. Schwartz (617) 918-4575 [email protected]
Marko Kozul, M.D. (415) 905-7221 [email protected]
Michael Schmidt, Ph.D. (617) 918-4588 [email protected]
Irene Lau (415) 905-7256 [email protected]
Rene Shen (212) 277-6074 [email protected]
Gena Wang, Ph.D. (212) 277-6073 [email protected] Life Science Tools Dan Leonard (212) 277-6116 [email protected]
and Diagnostics John L. Sullivan, CFA (617) 918-4875 [email protected]
Justin Bowers, CFA (212) 277-6066 [email protected]
Pharmaceuticals/Major Seamus Fernandez (617) 918-4011 [email protected]
Swati Kumar (617) 918-4576 [email protected]
Specialty Pharmaceuticals,
Generics
Jason M. Gerberry, JD
Christopher W. Kuehnle, JD
(617) 918-4549
(617) 918-4851
[email protected] Medical Devices, Cardiology & Danielle Antalffy (212) 277-6044 [email protected] Orthopedics Richard Newitter (212) 277-6088 [email protected]
Robert Marcus, CFA (212) 277-6084 [email protected]
Healthcare Technology David Larsen, CFA (617) 918-4502 [email protected] & Distribution Christopher Abbott (617) 918-4010 [email protected]
Sr. Editor/Supervisory Analyst Mary Ellen Eagan, CFA (617) 918-4837 [email protected]
Supervisory Analysts Robert Egan [email protected]
Amy N. Sonne [email protected]
Research Assistant Paul Matteis (617) 918-4585 [email protected]
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