https://rodman.bluematrix.com/docs/pdf/a9de2b4f-f08b-415e-87f6-2e503e6a6...

Interesting tidbits from last week (November 16- November 20)
1) A tough start to the week for Poniard: Picoplatin shows activity, and SPEAR comes close, but does not meet
primary endpoint: On Monday morning, Poniard (PARD Market Perform) announced that the Phase III SPEAR trial of
picoplatin in second-line small cell lung cancer did not to meet its primary endpoint of overall survival (O/S). Preliminary
analysis of the data, based on 320 evaluable events (patient deaths), showed a hazard ratio of 0.82 (p=0.089). The
Statistical Analytical Plan of the trial, as agreed to in an SPA with the FDA, was 90% powered to show a 33% reduction in
risk in death for picoplatin treatment plus best supportive care (BSC) compared with BSC alone (HR=0.67; p=0.05).
What happened? Patients in the BSC arm seem to have done better than expected, possibly due to an imbalance
in the use of chemotherapy. The preliminary analysis of the data seems to indicate that the pico arm behaved similarly
to what was seen in the Phase II trials, i.e. that patients in the pico arm had an O/S high enough that if the BSC patients
had behaved according to what the assumptions of the trial were, the O/S seen with picoplatin would have been enough
for the trial to be successful. According to management, the data it has seen thus far indicate there was an imbalance in
the use of chemotherapy between the two arms of the trial, i.e. that more patients on the BSC arm received chemotherapy
following progression, than those on the picoplatin arm, and this could have potentially led to longer-than-expected
median overall survival in the BSC arm.
Making its case with the FDA; a lot depends on what the subgroup dataset looks like. The company contacted the
FDA this morning and requested a meeting to discuss the data from SPEAR and the overall dataset from the pico trials.
Once it has the full dataset analyzed, management’s goal will be to convince the FDA to look past the fact that the trial
missed its primary endpoint, and given the unmet medical need in the setting, consider an NDA on the drug’s other merits,
including benefits to the subset of patients that did not receive chemotherapy after progression. According to the
preliminary analysis, if one looks at the patient group in the two arms that did not receive additional chemotherapy,
picoplatin did meet the primary endpoint of improving overall survival with statistical significance. We believe that, given
the current climate of rigidity and conservatism at the FDA, this will be a very difficult task for Poniard, but we will have a
more educated opinion once we gain better visibility on what the full data set from the trial looks like in terms of overall
survival in patient subgroups and secondary endpoints.
The three crucial issues that will have to be addressed: 1) The FDA’s input to Poniard (and potential partners by
extension) on whether the efficacy seen in this trial is enough to support an NDA in SCLC, 2) How the company will be
able to fund operations going forward, and 3) the future of a partnership for the development of picoplatin. The issue of a
partnership is, of course, further complicated on today’s news; we believe that any partnership decision will be postponed
until after the company’s meeting with the FDA, which will probably not take place until early next year. Finally, we see
Poniard as a company that still has many options in terms of its ability to fund further development of picoplatin, whether
that comes in the form of a secondary offering, use of the $60M equity line, funding through a partnership, or even other
options not currently on the table.
We downgraded PARD to Market Perform on the SPEAR news, but see value in picoplatin long-term. Despite this
week’s setback in SCLC, we continue to believe there is value in picoplatin longer-term and we will continue to monitor
the developments with the agency, along with the release of data from the colorectal and prostate cancer trials. In the
meantime, we remain on the sidelines on PARD, until further clarity becomes available on the future of the small cell lung
cancer program.
2) Provenge BLA Submission Accepted for Review On Friday, the FDA informed Dendreon (DNDN Market
Outperform) in writing that the company’s amended BLA for Provenge has been accepted for review as a complete
response, Class 2 Resubmission, and that the agency has assigned a PDUFA date of May 1, 2010. The amended BLA
includes data from the IMPACT trial, conducted under a SPA, that met the pre-specified primary endpoint demonstrating a
statistically significant improvement (p = 0.032) in overall survival in men with metastatic hormone refractory prostate
cancer. The amended BLA also contains additional information requested by the agency pertaining to chemistry,
manufacturing and controls for Provenge. As a reminder, the FDA held a meeting with Dendreon in May 2009 and the
agency confirmed that the results of the IMPACT trial would be sufficient to amend the Provenge BLA. During the May
meeting, the FDA and the company also reviewed the complete response letter item-by-item and discussed in detail how
the company would address deficiencies in the 2007 complete response letter. In our opinion, the collaborative effort
Biotechnology November 22, 2009
RODMAN & RENSHAW EQUITY RESEARCH 6
Table of contents
between the company and the agency bodes well for the chances of an eventual Provenge marketing approval. Please
click here for Ren Benjamin’s full report.
3) Vivus’ (VVUS Market Outperform) First Phase 3 Study of Avanafil Reaches Endpoints
The first Phase 3 study of avanafil (REVIVE) enrolled 646 subjects across four arms (n = 162 on placebo, n = 161 on
50mg/day, n = 161 on 100mg/day, and n = 162 on 200mg/day). The study included a four-week run-in period followed by
12-weeks of treatment. Patients appear to be well-matched across the drug and placebo arms. The results show a dosedependent
and statistically significant improvement on the SEP 2 endpoint (questions on the ability to achieve erection)
and the SEP 3 endpoint (questions on ability to maintain erection) versus the placebo. At the highest tested dose (200mg
daily) the ED severity score increased from 12.7 at baseline to 22.2 at the end of treatment (p=<0.001). The company
stated that a substantial fraction of patients reached a score of 26 (considered a threshold for normal erectile function),
but these results were not presented at this time. All doses of avanafil appear to be well-tolerated, with headache as the
most frequent treatment-emergent adverse event (7% avanafil vs. 1.2% placebo). One gunshot-related death was
reported for a patient on the 100mg arm, and does not appear to be associated with the drug. Please click here for Elemer
Piros’ full report.
What’s coming up this week? (November 23 – November 27)
Expecting a quiet Thankgiving week, with Telavancin PDUFA the main scheduled news item: Due to the
Thanksgiving holiday, we expect this to be a quiet week, at least in terms of scientific meetings, and FDA advisory
meetings. The only news we will be watching for will be the FDA decision on Theravance’s (THRX Not Rated) Telavancin
for the treatment of nosocomial pneumonia (NP). Hwoever, there has been talk that the PDUFA may be pushed back into
2010, especially since the agency may require an advisory committee meeting before deciding on the NP indication. We
remind investors that in September, the FDA approved VIBATIV (Telavancin) for the treatment of adult patients with
complicated skin and skin structure infections (cSSSI) caused by susceptible Gram-positive bacteria, including
Staphylococcus aureus, both methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains which was also
recently approved in Canada for cSSSI. The FDA approval earned Theravance a $20M milestone payment its
collaboration partner, Astellas (4503 Not Rated), and Astellas recently began notifying wholesalers that it is now accepting
orders for VIBATIV in preparation for a commercial launch, which kicked off on November 5th, 2009.