Never Mind The Delay, Amgen Puts D'mab on its Website

The Amgen team must have felt rather bullish that the FDA would approve denosumab today, since it is the PDUFA date. So they loaded this link on the biotech’s web site for anyone seeking information on reimbursement issues. [UPDATE: Amgen has removed the page and we didn't take a screengrab, but we have the new logo, below. UPDATE 2: Here's the page, rescued by commenter rob using Google cache.]

Never mind that it was still possible the agency would issue a complete response letter, which would cause a delay. And sure enough, that’s just what happened. The agency is requesting several items, including more detail about a post-marketing surveillance program (see the statement).

Reimbursement info is rather important to place on web sites, of course, given that more and more people are having difficulty affording their meds, especially during the recession. So this is a good public relations move, not just a genuinely helpful gesture. Pricing for denosumab, which Amgen has dubbed Prolia, is expected to cost about $1,000 a month, according to earlier reports, although that may change.

In any event, this isn’t the first time that Amgen has somehow gotten ahead of the FDA over a drug approval. In July 2008, BusinessWire issued a press release saying the agency had approved the Nplate blood clotting drug, albeit with certain risk management requirements. But the premature release embarrassed Amgen, which forced the news service to issue a retraction.

'false start' image via nfl.com

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

Pfizer's Brilliant Move to Nab Denosumab [With Poll Results]

People, people, people...why so angry? Apparently only 6% of you think the Pfizer-Wyeth deal is good for both companies. Just over 21% think it's a good deal for Pfizer only.

That's right, our snap poll has reached the 48th hour and is now closed. You can view the results here. Nearly 52% of about 300 votes cast say that the deal is a bad deal all around.

But let's put everything in the near-term aside for a second and let's think a little further down the road. The Wyeth acquisition puts Pfizer in the driver seat to grab the "potential blockbuster" (how many times have you heard that phrase?) osteoporosis drug denosumab from Amgen.

Hear us out. Remember, Wyeth and Amgen are partners on the anti-inflammatory biologic Enbrel (only a $3.8 billion dollar product). Amgen has said that there is absolutely no change to the relationship other than Pfizer will step into Wyeth's shoes.

So how do we go from there to Pfizer getting denosumab? Well, it's a leap, we'll admit. However, Amgen has said it may partner with another company to market and sell denosumab (assuming it gets approved; the application has been submitted to FDA). Our bet is, if they do partner, it will be with Pfizer. Who will have more sales experience and geographic reach than their Enbrel-partner Pfizer-Wyeth/Pfwyeth/Wyzer/Wy-Pfi?

That theoretical partnership would likely lock in Pfizer as the only viable buyer for Amgen when you take in ability to finance the deal, partnership exclusivity, scale, and cash.

What's that you say? Pfizer couldn't buy a company the size of Amgen after taking on Wyeth? We're not buying it. All arguments about whether or not that's smart strategy or whether it creates or destroys shareholder value aside, if anything, Pfizer has proven that it can continually buy and integrate large cap health companies.

What do you think? Are we crazy? We'd love to hear your comments but be gentle.

image from flickr user subkomandante used under a creative commons license

Amgen's Denosumab: NOW How Much Would You Pay?

Monty Hall is back, because it sounds like it may be now or never to secure a partnership with Amgen for one of the most eagerly awaited Phase III projects in the industry—the post-menopausal osteoporosis treatment denosumab.

Recall that Amgen is considering partnering the project, a once-unthinkable option but now an oh-so poignant sign of the times for an industry struggling to reinvent itself. Recall also that we offered you complimentary access to the profile of denosumab from Elsevier’s Inteleos database to help you decide how much to pay for a share of this potentially huge market opportunity—and to shoulder some of the risk that denosumab will instead become another spectacular Big Pharma flameout.

The latest development: Amgen has announced positive Phase III results in a big osteoporosis trial, involving about 8,000 patients studied for three years. The company certainly isn’t underplaying the results. R&D chief Roger Perlmutter told The New York Times that the trial “exceeded my expectations”--which seems hard to do, given that denosumab is essentially a bet-the-company project for Amgen at this point.

During Amgen's quarterly call July 28, Perlmutter explained his ebulliance. “The fact that we saw statistically significant reductions across all primary and secondary endpoints was really very impressive. I will also say that when you look at the safety database, you have nearly 24,000 patient years of experience here, so it is far greater than anything else that we had to look at. The fact that the safety profile is so balanced as compared to placebo was extremely encouraging.”

Now, we might take those comments with a grain of salt, since all indications are that Amgen is still actively soliciting interest in partners for the drug. As CEO Kevin Sharer noted during the call, the positive study “certainly doesn’t preclude the necessary work we will do to see what our options are.”

Amgen, of course, wants to raise the price of any deal: “This data certainly makes us more confident in our ability to launch ourselves,” Sharer declared.

And Amgen certainly faces other pressures. The company is deep into cost-cutting mode as it adjusts to the new, sharply reduced realities of its flagship EPO franchise. The last thing it wants to do is embark on aggressive new spending to build a massive primary care sales presence to support denosumab.

Sharer, understandably, declined to provide any estimates on how much Amgen would have to spend to support a go-it-alone launch—no sense showing all your cards, is there?

"Our view is that we've got really strong data here," he said. "We're going to have to take this data, look at it carefully, see what physicians think. But I just want to assure our shareholders that we're going to make a full and complete analysis and surface the right set of options, and I'm confident we'll pick the right one.”

Sharer also suggested that an internal launch might not be as expensive as the conventional Big Pharma model would suggest. "We see this medicine with its high science component as being something that will take the kind of high science and medicine approach that we've historically taken. So we do not see this as a normal general practitioner kind of sales product that you just throw in the bag."

On the other hand, Sharer clearly has a bit of a one-track mind when it comes to thinking about the importance of denosumab to Amgen. Asked to comment on Amgen's overall approach to infrastructure-building, and whether there might be any opportunities in the current climate of consolidation, Sharer replied succintly. "I can't imagine buying a company to acquire a sales force. That' s inconceivable."

So I guess those Genentech sales reps are going to have to look elsewhere....

Denosumab: Let's Make a (Hypothetical) Deal

Not too long ago, the idea that a top-ten biopharmaceutical company would out-license a potential blockbuster project was way out in left field. Not so much anymore.

Deutsche Bank analyst Mark Schoenebaum notes in a recent report to clients that Amgen stock has been on an upswing for the past few weeks, and rhetorically asks why. A major reason, says Schoenebaum, is that Amgen is saying it will likely partner its Phase III denosumab (d-mab, for the nickname inclined) in postmenopausal osteoporosis (PMO) instead of building its own 2000-strong field force to sell the product, should it get approved.

If you'll allow us to grab our plaid jacket and dust off our best Monty Hall impersonation, we'd like to take the scenario a step further. If Amgen wants to offload d-mab--what's the drug going to be worth to a partner? Should it partner a significant piece, like the PMO indication, or 50% of the entire package (d-mab is being investigated in preventing 'skeletal related events' in patients with breast and prostate cancers and a variety of other tumors--on Monday the company released positive top line data from one Phase III study, for example). What is the ideal scenario for Amgen?

You, dear readers, are the experts here. And so we turn to you. We're even going to give you the tool necessary to come up with your own NPV estimates: the profile of denosumab from Elsevier's Inteleos database. Click the link to access the free PDF, dig around, and leave your estimates in the comments ...

Come on, people. Let's make a deal.