The FDA, by granting CDX-011 accelerated approval track, has indicated that it views 011 efficacy/safety/unmet need favorably, and wants a subset of breast cancer pts (ie GPMNB+) to have earlier access to 011 as a treatment option. The success rate for cancer drugs that were tracked for accelerated approval by the FDA is very high, and in the last couple of years drugs that met the following key points have been 100% successful:
1. Targeting: CDX-011 targets the cancer bio-marker GPNMB. Even better, GPNMB is a novel biomarker and the FDA looks favorably on the targeting of new cancer markers (CLDX owns the IP for this molecule).
2. Target validation: in the EMERGE PII, pts in the IC control group who had more GPNMB expression also had worse outcomes. Also, pts who had more GPNMB expression also had better relative responses to CDX-011.
3. A companion diagnostic assay for the target that is reliable, reproducible and will be available nationwide. CLDX has demonstrated that it can assay for GPNMB marker in BC pts and can stratify magnitude of expression as well as localization of GPNMB in tissue specimens.
4. Patient selection: this is critical for the successful completion of pivotal trial. In the PII, CLDX was able to identify the pts who would respond best to CDX-011 relative to standard of care. This group consisted of the subset of high GPNMB( 25%)/ TNBC pts, although all pts expressing 5% GPNMB benefited with a 50% improvement in overall survival (after correcting for cross overs from IC to 011).
5. Safety: like most targeted drugs, CDX-011 has a relatively mild AE profile, with predictable and manageable side effects.
6. Efficacy: in the EMERGE trial, CDX-011 showed a 50% improvement in overall survival over IC (after correcting for cross over pts), and a doubling in survival and PFS in the high GPNMB/TNBC group.
Pivotal trial for accelerated approval:
1. Accelerated approval track means that CLDX will able to use surrogate markers (response rate and/or PFS) as indicators of efficacy instead of OS in order to complete the trial and receive marketing approval more rapidly.
2. The best option would be to go for high GPNMB/TNBC pts, with CDX-011 being used as a third line intervention. Since there are no good treatment options currently available as third line for these pts, the use of an active control can be bypassed- this would mean a single arm pivotal trial for 011.
3. Possible trial designs: an expansion of the PII high GPNMB/TNBC subset. There were already 12 pts treated with 011 in this group, and adding more pts to confirm the efficacy seen previously may be sufficient for FDA approval. A more likely scenario is initiating a new trial, single arm with about 80 pts high GPNMB/TNBC, to confirm the results seen in the smaller PII subgroup.
4. Duration: the whole point of accelerated approval track is to get the drug to pts as soon as possible, so typically these trials and FDA approval don't take very long. For example, crizotinib for non-small cell lung cancer received accelerated approval 3 years after the first pt entered the PI trial; vemurafenib for BRAF melanoma was approved 4 years after the first patient was enrolled in the PI trial (yes, that's PI (!)). CDX-011 has taken a more circuitous clinical path, but if we take the PII as the starting point, with July 2010 as the date when the first patient was enrolled, a 4 year duration for accelerated approval would mean July 2014 for FDA approval. For reference, response rate is obtained in 1.5-2 months from pt enrollment, and the median PFS in EMERGE for high GPNMB/TNBC was 1.5 months for IC and 3 months for CDX-011 pts.
Bottom line: the regulatory situation for CDX-011 looks very favorable, and that opinion is shared by investors who picked up 2.5 million CLDX shares today, and even more so by investors who are shelling out $80M for the offering @7.50. CLDX is in a very strong position with CDX-011, the rest of the pipeline and the financial arsenal to drive the pipeline forward to FDA approval and marketing.
LV...we know they do an 80 patient initial group and than review them for any Protocol Changes going forward....given the Notoriety of Glemba now, and what has transpired w/ T-DM1 what can we expect on enrollment once we start...pretty rapid or what? The 2:1 suggest very good odds on Glemba?
Sentiment: Strong Buy