Who's Got Game in Antibody Development?
[This has been kind of a slow place recently. A month since my last post. I fished up this summary on the net. Thought-provoking. Perhaps Abgenix with their heavy investments in production capacity and product- and process-development is up to something. If so, someone will take them out - one way or another. As the article notes, there are not so many valid targets available any more. Erik]
Antibodies are back in vogue. At the American Society of Clinical Oncology annual meeting in May, Genentech impressed clinicians and investors with efficacy data from its Phase III antibody, Avastin, helping fuel a rally in biotech stocks. Five months earlier, Abbott successfully registered its rheumatoid arthritis antibody therapy, Humira. Four major antibody drug candidates could hit the market this year. Not only that, fears of a commercial bioprocessing bottleneck—which dogged Immunex two years ago, leading to its acquisition by Amgen—seem to have abated.
Because of the complexity and cost of bioprocessing, the antibody development crowd comprises two distinct cliques: those with bioprocessing capability, who can take a validated target and expeditiously develop a fast follower, and those with some clever antibody engineering technology—the ability either to make and select for the best antibodies against a novel target, or to re-engineer them for special properties.
The handful of companies in the first group—including Genentech, Amgen, Biogen, and Abbott—have dominating advantages because they have already spent the money on building bioprocessing capabilities. Because process varies little from one antibody to another, they can wait for and quickly pounce on fast-follower opportunities, expanding production capacity in a modular fashion as demand requires—they don’t need to take target risk. Because there are only a few of them, they don’t have to worry very much about price-cutting new competitors and can focus on building franchises and marketing. They also have the clout to in-license or make acquisitions to further entrench their positions, as Amgen did when it bought Immunex. And since they control the output, their stock prices tend to increase with each product approval—theirs or someone else’s—giving them even more capital with which to in-license and grow their franchises.
What’s becoming clear is that antibodies are ideal candidates to be fast followers against known drug targets—led by Genentech with Her2 and Abbott with TNFa, the target of Humira. And what’s equally clear is that only that select group of companies with bioprocessing expertise and large-scale production capacity will be able to develop an antibody drug quickly, to minimize the risk that a lower-priced, market share-stealing competitor will stalk them. That small oligopoly can therefore spend their time building therapeutic franchises around large molecules, including in-licensing late-stage products, and growing their markets.
Those companies with the muscle to adopt the fast-follower approach can make and test new antibodies relatively quickly and with confidence that the target is druggable, and even engineer them for improved properties that enable the drugs to better compete against or be used in combination with compounds already developed against those targets—either humanized predecessor antibodies or small molecules.
Of course, smaller companies cannot buy their way into the game, nor can they compete in the more mature world of fast followers: they have to look elsewhere for leverage. In keeping with their greater appetite for risk, biotechs, with access to a slew of genomics information and putative drug targets, may therefore be willing to accept the higher attrition rates that come with working around novel, less-validated targets. The best hope for this group is for them to use their antibody technology development expertise to come up with good drugs against novel targets in diseases where no antibody treatments currently exist. The novelty of the resulting products—which presumably will synergize rather than compete with small-molecule therapies—will give them the kind of leverage they haven’t been able to get from platform dealmaking: they’ll be rewarded for their risk-taking by being able to retain a significant share of such products, even if they ultimately choose to turn to an established bioprocessor to make them.
But because antibody platform companies have yet to demonstrate that they can successfully make the transition to product developers on either end of the spectrum—R&D, on one side, and bioprocessing, on the other—it’s hard to declare these companies players yet: Abgenix, Medarex, PDL, MorphoSys all need to demonstrate an ability to take a target all the way through the clinic, and at the same time be able to develop or access manufacturing on reasonable terms. Despite those firms’ attempts to minimize those risks, they are formidable, including the prospect of lots of delay and expense at Phase III if adequate processes aren’t built in early in development—a risk amplified as they take more shots on goal and are forced to make more and more portfolio development choices based on early clinical data.
And importantly, besides Humira (which of course was developed by BASF, not one of the antibody platform-turned-product biotechs), there’s little evidence of having the ability to optimize the antibody against a target. That may be because while antibodies are a central tool in pharma genomics programs, they’ve been used as a research tool to validate the target, not the antibody itself as a drug. For example, Pfizer has been working with Abgenix’s technology for six years. But it has yet to get an antibody molecule through proof-of-concept testing, when presumably such trials would be publicly known. One reason could be that it was using antibodies as a target validation tool, at best using the molecules as experimental medicine to test for activity—the path on which antisense started, and more recently RNAi.
If you’re not already in the game, how can you get into it?
The route that Abbott and Amgen took, buying BASF and Immunex, respectively, is largely closed now, because there’s simply no one else out there who’s available. Thus, in the current risk-averse, show-me-a-product-today environment of both pharma and biotech, it seems the players will remain the same.
windhover.com |
