So the biopharma news is abuzz by the wipeout over at $AFFY, as they and Takeda pull Omontys off the market after a number of deaths by anaphylaxis.
For those not familiar, Omontys, is an erythropoietin stimulating agent (ESA)..or actually, a synthetic peptide erythropoietin memetic. The obvious winner here will be Amgen, as its EPO/ arnesp franchise should gain (or at least not lose) share from the newer product, now out of the scene.
Now Ligand & GSK's Promacta focuses its stimulation on platelets... not erythrocytes. But both have the same progenitor cells if you go back far enough. Still, the MOA of peginesatide, as it mimics erythropoietin, our read is its removal should have little bearing on market potential for Promacta.
But ... it could throw the door wide open for market potential of Ligand's unpartnered EPO Receptor Agonist Program.
To quote from the $LGND webpage, "Erythropoietin (EPO) acts on its receptor to stimulate the differentiation of bone marrow hematopoietic cells to form red blood cells. Various recombinant human EPO derivatives are marketed as erythropoiesis-stimulating agents (ESAs) for the treatment of anemia due to renal failure or cancer chemotherapy (e.g., AranespTM, EpogenTM, EprexTM, and ProcritTM). We have discovered a series of orally-available, small molecule agonists of the EPO receptor that should provide additional benefit in the treatment of anemia with improved safety, tolerability, and patient acceptance due to the convenience of oral administration and the lack of excessive erythropoietic stimulation. In December of 2010, we presented preclinical data on our EPO receptor agonist LG5640 at the 52nd American Society of Hematology (ASH) Annual Meeting, highlighting its unique mechanism of action and selective profile. In addition to LG5640, highly potent and selective EPOR agonists have been identified that display oral bioavailability in the mouse, rat and monkey, and have a desirable in vitro and in vivo safety profile for preclinical development. We are seeking a partner to advance pre-clinical and clinical development, and commercialization."
Unlike the synthetic peptide Omontys, small mol approaches like LG5640 and the next gen mols at Ligand would likely not share the same molecular causes of the reaction, which we expect is an off target activity. While the event may cause a bit of a step back till the cause is well understood, we anticipate it may swing the balance away from other synthetic peptides toward small molecules. At a minimum, this event will decrease the competition in the ESA space. In other words, $LGND should benefit... in the form of a better / richer R&D collaboration / out license deal.
I agree that this has absolutely no impact on Promacta. Omontys is a protein therapeutic and there are at least 10X more things that can go wrong with a protein than a small molecule and it's a lot harder to catch them as well. Small molecules can be rigorously tested using basic chemistry...with a protein it's not that easy. You need to worry about anti-drug antibodies, biological contaminants from manufacturing, etc and most of these things require biological assays and a good deal of effort to detect reliably.
My guess on what happened with Omontys is that there must be a subset of patients out there with pre-existing antibodies to PEG from exposure to pegylated drugs in the past, and this was the cause of the fatal anaphylaxis. AFFY should be able to easily test for this if they have even the slightest idea of what they are doing. This type of bioanalytical testing always gets overlooked until something like this happens. For sure, anyone trying to move a new ESA forward is going to face some serious regulatory scrutiny, and a small molecule ESA is probably looking quite attractive right about now.
It's sad to see this happen but personally I love the news.
As all the deaths occurred within 30 min of first dose of Omontys, the anti-PEG Ab theory is a distinct possibility. Will be interesting to hear more details of the cases, for if you are correct, it might affect many drugs and therefore companies. And I also agree could open the door for a diagnostic... or at least some exposure test protocol... which might allow the drug to return. But the challenge is the only real advantage I can see with Omontys over EPO is convenience, and it is not that much of an advantage over Aranesp.