Replies to post #90332 on Biotech Values

[DewDiligence]

The ONJ rate of ~2% in the D-mab arm vs ~1% in the Zometa arm is somewhat worrisome; however, ONJ is clearly a more acceptable SAE in a trial for metastatic cancer than in a trial for, say, osteoporosis. Hence, I’m inclined to think the ONJ numbers won’t derail D-mab’s approval in metastatic cancer or derail its commercial uptake in this setting.

One observation from the D-mab data in HRPC is that it seems to make little difference whether one measures the time to the first skeletal-related event or one measures the rate of multiple SRE’s. The former metric had HR=0.82 (for D-mab relative to Zometa) with a 95% CI of [0.71,0.95], while the latter metric had HR=0.82 with a 95% CI of [0.71,0.94]—an almost identical outcome.

[jbog]

P3, Deno

I highlighted the ONJ side effect because it seemed to creep up to rather high levels in comparison.

Years ago the absence of ONJ in the early Deno trials caused the street to think that it would be a huge selling point.

IV Bisphosphonates versus Denosumab (AMG-162)
In Preventing Bone Turnover

• Julie Gralow, PharmD, University of Washington Cancer
Care Alliance, Seattle, Wash.

Regardless of prior intravenous (IV) use of bisphosphonates,
cancer patients with various tumor types who received
denosumab, an investigational agent, had decreased markers
of bone turnover, according to Dr. Gralow. She noted that
although IV bisphosphonates are the current standard of care,
“they have limitations in both efficacy and safety.”
Specifically, regarding safety, IV bisphosphonates are as -
sociated with renal toxicity; first-infusion effects, including
fever, and chills; and osteonecrosis of the jaw (ONJ). Denosumab
is a fully human monoclonal antibody that binds and
neutralizes receptor activator for nuclear factor-kappa B ligand
(RANKL). RANKL accelerates bone turnover and has been
found to have harmful effects on bone volume and strength.
Denosumab has demonstrated no renal toxicity, no first-infusion
effects, and no ONJ to date, Dr. Gralow said

[DewDiligence]

Zometa fails to extend DFS in adjuvant breast-cancer trial that tested (chemo)+(aromatase inhibitor) ± Zometa:

http://www.reuters.com/article/idUS185738+09-Dec-2010+HUG20101209?feedType=RSS&feedName=huginPressRelease&rpc=43

The failure is not a big deal financially for NVS because Zometa goes off-patent in major countries in about two years.