Avid Bioservices Inc (CDMO)

[cjgaddy]

Early comp. of Bavi vs. Avastin in Frontline NSCLC: Peregrine’s 2008-2009 n=49/India single-arm signal-seeking Ph.2 trial vs. Avastin’s 2001-2004 n=434 Ph.3 Accel-Apprv. Confirmation trial “E4599”. Updated with more thorough discussion of differentiating factors between patient demographics and baselines treated in the 2 trials.
As mentioned below, we anxiously await results from the 2 ongoing Bavi randomized NSCLC trials:
1. F. Phase IIb Bavi+Doce vs. Refractory NSCLC (randomized, double-blinded, placebo-controlled, n=120, registrational) http://clinicaltrials.gov/ct2/show/NCT01138163 (37 sites)
2. G. Phase IIb Bavi+CP vs. Front-Line NSCLC (randomized, unblinded, confirmatory) http://clinicaltrials.gov/ct2/show/NCT01160601 (28 sites)

Results for the completed Ph.2 Bavi+CP Frontline NSCLC signal-seeking trial (dosed 6/2008-10/2009 n=49 http://clinicaltrials.gov/ct2/show/NCT00687817 ) were released 6-6-10 at ASCO’10 (ORR=43% PFS=6.1mos – see http://tinyurl.com/2g5cqof - also of note, see the TWO “100% max. reductions in tumor size” bars in the Fig1 waterfall plot), with a MOS=12.4mos followup in a 6-15-11 PR ( http://tinyurl.com/3fcz5ok ). The 6-15-11 PR compared the Bavi+CP results with “versus historic control [CP-only] data of ORR=15%, PFS=4.5mos, and MOS=10.3mos”, taken from the E4599 Avastin+CP Frontline NSCLC Ph.3 trial reported 12-2006 in NEJM (Sandler et al). No comparison to Avastin+CP was made in the PR, but the 6-17-11 LifeTech-Cap. ‘Morning-Note’ added the comparison to Avastin+CP’s results from E4599/n=434: ORR=35%, PFS=6.2mos, MOS=12.3mos ( http://lifetechcapital.com/ltc/wp-content/uploads/2011/06/Morning-Note-06-17-11-PPHM.pdf )
[“CP” = Carboplatin+Paclitaxel]

Putting all that together, we have:

 
 Result      CP-Only(n=444)     Avastin+CP(n=434)    Bavi+CP(n=49) 
 Obj. Resp.      15%                 35%                43% 
 Median PFS     4.5mos              6.2mos             6.1mos 
 MOS           10.3mos             12.3mos            12.4mos 
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 Avastin data: http://www.nejm.org/doi/pdf/10.1056/NEJMoa061884  
 Bavi data: 6-15-11/MOS-PR http://tinyurl.com/3fcz5ok & ASCO'10 http://tinyurl.com/2g5cqof 

BUT, that’s not the end of the story…
With Mojo’s 6-30-11 ECOG0-vs-ECOG1 revelation ( http://investorshub.advfn.com/boards/read_msg.aspx?message_id=64742382 ), we now have a 3rd Bavi-favorable distinction between patient demographics & baseline characteristics of the n=49 Ph.2 Bavi+CP/FrontlneNSCLC signal-seeking trial vs. a most interesting comparator, the n=434 Ph.3 “E4599” Avastin+CP/FrontlneNSCLC accelerated approval confirmation trial reported in 2006:
• The Bavi+CP results were accomplished using less chemo (175mg-v-200mg & AUC5-v-AUC6) than used in the Avastin+CP trial.
• The Bavi+CP results were accomplished despite including harder-to-treat Squamous patients (8/49=16%; they yielded ORR=25%), totally excluded in the Avastin+CP trial.
• The Bavi+CP results were accomplished despite treated a higher % of sicker frontline-NSCLC patients (6%/ECOG0, 94%/ECOG1) than were treated in the Avastin+CP trial (40%/ECOG0, 60%/ECOG1).
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ECOG-STATUS COMP. FOR BAVI VS. AVASTIN FRONTLINE-NSCLC TRIALS:
Note: ECOG1 = sicker than EGOC0 – see below.
• Avastin+CP (Ph.3 E4599 n444): MOS = 12.3 mos. => ECOG0=40% ECOG1=60%
• CP-only (Ph.3 E4599 n444): MOS = 10.3 mos. => ECOG0=40% ECOG1=60%
• Bavi+CP (Ph.2/India n=49): MOS = 12.4 mos. => ECOG0=4% ECOG1=96%
Avastin data: http://www.nejm.org/doi/pdf/10.1056/NEJMoa061884
Bavi data: 6-15-11/MOS-PR http://tinyurl.com/3fcz5ok & ASCO'10 http://tinyurl.com/2g5cqof
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ECOG PERFORMANCE STATUS [higher# => more advanced disability]
Grade ECOG
0 = Fully active, able to carry on all pre-disease performance without restriction
1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2 = Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours
3 = Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4 = Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5 = Dead
http://ecog.dfci.harvard.edu/general/perf_stat.html

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All of which seem to correlate to Steve King encouraging public comments about Bavi’s Frontline NSCLC results from the Ph.2 signal-seeking trial reported at ASCO’10 ( http://tinyurl.com/2g5cqof ) and in the 6-15-11 MOS=12.4mos PR ( http://tinyurl.com/3fcz5ok ):
• “the one we’re most excited about” 7-30-09 http://tinyurl.com/lqwedd
• “the most outstanding results to date” 9-1-09 http://tinyurl.com/n6gq7y
• “perhaps the most remarkable results” 1-13-10 http://tinyurl.com/yb7v2u4
• “the NSCLC data is really just outstanding” 3-17-10 http://tinyurl.com/ye9v7jq
- - - - -And the kicker:
• "We refer to this new this [Ph.2B randomized Refractory NSCLC trial] as a Registrational Phase II Study, because we believe that if we have results anywhere near approaching what we saw in the earlier [India] study, it could be a conduit for Accelerated Approval.” 3-17-10 http://tinyurl.com/ye9v7jq

ASCO’10: Ph.2 Bavi+CP/NSCLC (India n=49), #7589, 6-6-10 – Interim Results http://tinyurl.com/2g5cqof . . .










= = = = = = = = = = = = = = = BAVI TRIAL USED LOWER LEVELS OF CHEMO C/P:
This from the 6-15-11 “Morning Note on PPHM” issued by LifeTech Cap. => “Investors should note that these [Frontline NSCLC] results were achieved using less Paclitaxel (175mg/m2 vs. 200mg/m2) and less Carboplatin (AUC=5 vs. AUC=6) [than the E4599 Avastin+CP NSCLC Trial].”
6-15-11: LifeTech-Cap. (S.Dunn/W.Dawson) ‘Morning Note’ on PPHM:
http://lifetechcapital.com/ltc/2011/06/peregrine-pphm-note-06-15-11-2/
PDF: http://lifetechcapital.com/ltc/wp-content/uploads/2011/06/Morning-Note-06-15-11-PPHM.pdf
“On 6-15-2011, Peregrine announced a promising 20% improvement in median overall survival (MOS) of 12.4 months versus 10.3 months from a historical control in their Phase II trial of bavituximab + carboplatin & paclitaxel in patients with previously untreated, locally-advanced or metastatic non-small cell lung cancer (NSCLC). In addition, the safety profile of bavituximab when combined with carboplatin & paclitaxel did not appear to increase known chemotherapy toxicity confirming the interim results shown at ASCO 2010 (Abstract# 7589) [ http://tinyurl.com/2eoz96r ]. Investors should note that these results were achieved using less Paclitaxel (175mg/m2 vs. 200mg/m2) and less Carboplatin (AUC=5 vs. AUC=6). An addl. 86 patient Phase II trial is ongoing using a blinded active control arm and excluding the squamous NSCLS sub-type.”

*This chart comparing Bavi+CP/n=49 vs. CP-only/n=444 vs. Avastin+CP/n=434(E4599) in Frontline NSCLC is from a follow-up “Morning Note on PPHM” by LifeTech-Cap’s Stephen Dunn, issued 6-17-11 (they added the Avastin+CP comparison):
PDF: http://lifetechcapital.com/ltc/wp-content/uploads/2011/06/Morning-Note-06-17-11-PPHM.pdf


= = = = = = = = = = = = = = = = =SQUAMOUS NSCLC:
In the BaviCP Ph.2 NSCLC trial, 8 patients with Squamous histology (8/49=16% - they yielded ORR=25%) were treated before Squamous patients were excluded in Stage2…
6-6-10 ASCO'10 Bavi/NSCLC: ORR=43% (21/49), PFS: 6.1mos (n=49)
…Plus, Fig1 of Poster #7589 shows: 1) 2 100% Red's (4.1%) and 11 Resp>50% (22.4%)
==> http://tinyurl.com/2g5cqof
ASCO’10 #7589: ”Phase II Study of Bavituximab + Paclitaxel/Carboplatin in Untreated Locally Advanced or Metastatic NSCLC: Interim Results”
Raghunadharao Digumarti, Sunday, 6-6-10, 8:00am-12:00pm
http://clinicaltrials.gov/ct2/show/NCT00687817 (India, 21+28=49)
ABSTRACT: Bavituximab, a novel chimeric IgG1 monoclonal antibody which targets the membrane phospholipid, phosphatidylserine complexed with B2-glycoprotein I on tumor vasculature, was tested in combination with paclitaxel and carboplatin in a multicenter open label, phase II trial to examine the clinical response rate and safety in adults (n=49) with untreated locally advanced or metastatic non-small cell lung cancer. . . To date, median PFS in the initial 21 treated is 6.2 mos. . . AEs have been reported by 44/49 (89.8%) treated subjects with the majority mild or moderate in severity. The 6 most common AEs have been pyrexia (28.6%), diarrhea (26.5%), alopecia (26.5%), anemia (22.4%), neuropathy (20.4%) and pain (20.4%). Safety analysis revealed 45 SAEs in 19 subjects (incl. 2 deaths due to myocardial infarctions and one death due to hemoptysis in 1 of 8 subjects with squamous histology). Accrual of squamous cell carcinoma was discontinued. . . Bavituximab. . .appears to be safe and well tolerated when given in combination with paclitaxel and carboplatin and has produced a promising 52% ORR using RECIST criteria in an initial group of patients with locally advanced or metastatic NSCLC.
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Lung/Squamous is extra-tough. This Avastin+CP Ph2/3 trial excluded Squamous as well…
• Avastin+CP/NSCLC (Sandler), 35% ORR (133 of 381) – best resp. reported. [ 2006 Ph2/3 ‘E4599’: Excl. Squamous**]
http://tinyurl.com/dbvh4e
**Note: “In prev. clinical experience with Avastin+CP in NSCLC, patients with ‘squamous’ cancer had a higher risk of experiencing life-threatening or fatal pulmonary bleeding. Squamous cells are a kind of cell that form in the lining of the air ducts in the lung. Because of the risk of bleeding attributed to this population, patients with NSCLC classified as predominantly squamous histology were not included in the [Avastin] E4599 trial.” http://tinyurl.com/cfk9ao
SQUAMOUS CELL CARCINOMA
This accounts for about 30% of all lung cancers. Again it’s linked to a history of smoking (it’s very unusual in non smokers) and affects mainly men. As its name suggests, the cancer affects the squamous cells which are thin flat cells which when infected tend to resemble pearl like nodules. They are more common in the central airways and can grow large enough to block the airway and cause lung collapse. Because the cancer is near the airway it can cause early symptoms such as a cough and the production of phlegm.
http://www.guide4living.com/lungcancer/non-small-cell.htm

= = = = =WE AWAIT RESULTS FROM THESE 2 ONGOING RANDOMIZED TRIALS…
F. Phase IIb Bavi+Doce vs. Refractory NSCLC (randomized, double-blinded, placebo-controlled, n=120, 'registrational')
Protocol: http://clinicaltrials.gov/ct2/show/NCT01138163 (24 U.S. + 11 India + 2 RepGA = 37 Sites as of 5-24-11)
...Also listed in: India's CTRI registry ctri.in#2191 (12 sites a/o 3-20-11)
…Per CEO S.King, 3-17-10/Roth: "We refer to this trial as a Registrational Phase II Study, because we believe that if we have results anywhere near approaching what we saw in the earlier [India] study, it could be a conduit for Accelerated Approval.”
...6-4-10: Ph.2b randomized reg. trial Open for enrollment: http://tinyurl.com/25v22qk
……"up to 120 refractory patients at ~30 clinical sites; goal: fully-enroll by mid'11, topline data by y/e'11."

G. Phase IIb Bavi+CP vs. Front-Line NSCLC (randomized, unblinded, 'confirmatory')
Protocol: http://clinicaltrials.gov/ct2/show/NCT01160601 (17 U.S. + 9 India + 2 RepGA = 28 Sites as of 5-24-11)
...Also listed in: India's CTRI registry ctri.in#2190 and WHO's registry who.int#1402
…Per J.Shan (VP/Clin+RegAffairs), 7-14-10 CC: "This trial is intended to confirm in a randomized setting the results from our Ph.2 signal-seeking NSCLC trial which showed 43% ORR, more than double the generally accepted chemo ORR of under 20% in numerous publications. Favorable results could then lead to an end of Ph.2 meeting with the FDA, with possibly a pivotal Ph/3 trial for front-line lung cancer, our 2nd potential regulatory pathway for bavituximab."
...7-14-10: U.S. Ph.2b randomized trial initiated http://tinyurl.com/27kxksl
……up to 86 front-line patients at ~20 clinical sites; goal: enrollment comp. by mid'11.

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BAVI-vs-AVASTIN COMMENTARY BY IHUB’S FIREFOX, #65529 6-30-11:
“…Let's remember that randomized Ph IIb trial results usually come in worse than signal seeking Ph IIa results. So in order not to disappoint the markets when randomized results come out, it was smart of SK and Garnick to understate how well Bavi did in signal seeking trial by not highlighting the ways in which our patient patient population was sicker, or received less chemo, than Avastin population. The 3 distinctions CJ summarizes in his post 65518 give us a margin of safety that should make us all sleep better as we approach Q4 2011 and Q1 2012 reports on the randomized NSCLC results.” http://investorshub.advfn.com/boards/read_msg.aspx?message_id=64779682

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A 4-2-2011 MDA Presentation with wealth of info. on the battle against NSCLC:
http://community.e-baptisthealth.com/conferences/docs/2011Lung_Advanced_NSCLC.pdf