D-mab Trumps Zometa With Top-Line Cancer Results

Amgen last night released top-line results from a Phase III head to head study pitting its most important future drug, denosumab, against Novartis’ Zometa in breast cancer-linked bone complications.

The results look good—better than most expected. Denosumab appears to be not simply non-inferior to Zometa (the primary endpoint of the study) but superior to Novartis’ incumbent drug—itself pretty potent--in terms of delaying the time to first and subsequent skeletal-related events.

Deutsche Bank’s Mark Schoenebaum describes these efficacy results as a “best-case outcome”, having himself put the odds of the drug’s showing superiority at just 40%. (Overall survival and time-to-progression were the same for the two drugs.)

All this matters much to Amgen. The Big Biotech’s relying more heavily than is comfortable on this single late-stage compound to secure its future growth and independence. (Remember, its EPO- and cancer-focused base business is in steady, irreversible decline.) And although the drug is widely expected to be approved for post-menopausal osteoporosis first, likely in October this year, the cancer indication could be worth just as much—about $1.5 billion in peak sales--according to some analysts.

And cancer’s what Amgen knows about—it already sells Neupogen, Neulasta and Aranesp. The Big Biotech has absolutely no experience in PMO, a complicated, busy market dominated by cheap oral generic bisphosphonates. There’s widespread skepticism about the drug’s commercial potential in this indication as a result; DB reckons the drug could capture 10-20% of the market at peak (it’s a big market, mind you: $8 billion).

Schoenebaum in May described the outcome of this Phase III cancer trial as biotech’s “biggest data event” for 2009. (The d-mab PMO data released last year—also better than expected—may well have been 2008’s “biggest event”, too, mind you) Full efficacy and safety data from this breast cancer trial will be presented at a meeting later this year, and results from a second Phase III study in advanced solid tumor/multiple myeloma patients (there are four in total) are also due before year-end.

The probability of superiority in this second trial, plus another in prostate cancer due to report in 2010 has now risen, according to analysts at Leerink Swann. And when it comes to potential oncology indications, Amgen’s not leaving any stone un-turned: it recruited 11,000 patients for its d-mab cancer trials, out of a total of 19,000.

Look out Novartis, then. The Swiss group has enjoyed dominance of the SRE market since Zometa’s approval in 2001, with almost $1.4 billion in worldwide 2008 sales. It quickly displaced (Novartis’ own) Aredia, another IV bisphosphonate, thanks to a shorter infusion time, but d-mab’s subcutaneous delivery will likely trump that.

And it doesn’t look as if Novartis will have much safety ground to stand on, either. Indeed, the drug’s growth has recently stalled in part, says Schoenebaum, because of concerns over osteo-necrosis of the jaw (ONJ), kidney toxicity and efficacy beyond two years. The d-mab data suggests, according to Amgen's PR, “no statistically significant” difference between the rate of ONJ in the two treatment arms, equally “balanced” rates of infectious adverse events (an initial concern with d-mab) and an overall incidence of events “consistent with what had previously been reported for the two agents.”

All the same, since Zometa goes generic in 2013, and there are already some filings, Amgen will have to move fast to translate this apparently starry trial data into equally sparkling sales growth. Payor pressure means even a ‘superior’ drug may struggle if generic IV bisphosphonates get cheap enough. (Leerink Swann expects Amgen to price d-mab higher than the $12,000-p/a Zometa.)

image by flikrer robinbyles used under a creative commons license