Very nice article, unsure whether anyone read earlier!
Brief Overview: Summary of the Affymax/OMONTYS Story
Affymax's sole drug product is OMONTYS® (peginesatide) Injection ("OMONTYS"), which was approved by the FDA in 2012 and well received by the medical community as a treatment for anemia due to chronic kidney disease (CKD) in adult patients on dialysis. The drug seemed destined to break Amgen's (AMGN) monopolistic stranglehold on this large population therapeutic area, as both drug sales and AFFY share price rocketed.
Then the trouble started. (The cascading waterfall starts here.)
As it turned out, the drug performed very well in a controlled clinical trial environment. Both safety and efficacy surpassed expectations. However, outside the clinical trial environment and into the dialysis center environment where OMONTYS was distributed, results were different and in a very, very small percentage of patient cases, tragic.
Hypersensitivity reactions were reported for approximately 0.2% of the first 25,000 patients receiving OMONTYS, with approximately a third of these reactions serious in nature, including anaphylaxis requiring prompt medical intervention, and in some cases hospitalization. Three patient deaths were attributed to OMONTYS administration, though it is yet not settled whether the cause was the drug or human error, though statistically it points to human error as the most likely possibility.
Affymax and its partner, the global Japanese pharma company Takeda (TKPYY.PK) (eighth largest pharma in the world), made the decision to VOLUNTARILY recall OMONTYS in February of this year. All lots of OMONTYS were affected by this recall. Takeda has committed to fully investigate exactly what happened to those affected patients in the dialysis centers through what it terms a "root cause analysis."
It should be noted that allergic and anaphylactic reactions did occur with a very, very small number of patients during the clinical trials, but the reactions were less than with other erythropoiesis-stimulating agents (ESAs) on the market, particularly those drugs marketed by Amgen, who has enjoyed a monopoly in this category dating back to the 1990s. ESAs are the category of drug to which OMONTYS belongs.
Nothing Is Certain, But It's A Sensible Conclusion That OMONTYS Returns To Market
I believe the safety problems that led Takeda to withdraw OMONTYS will be investigated, identified, and resolved in due time. In my research OMONTYS fatalities appear to be similar or lesser in scope to MANY other drugs currently on the market and particularly other ESA's which have had reactions and fatalities along the entire usage life-cycle.
Here is some evidence supporting my opinion that OMONTYS will resurface:
When administered subcutaneously (under the skin), the drug works without any serious reactions. Serious reactions have only resulted from intravenous (in the vein) injections.
All three fatalities occurred in a few dialysis centers believed to be owned by the same company, Fresenius (FMS), who has a mound of safety issues filed against it. These fatalities occurred relatively soon after FDA approval.
Takeda may identify post-approval patient reactions that did not surface during the extensive trials, and then the company will need to take definitive and demonstrable steps to remedy those newly identified reactions before any discussion of OMONTYS's return. But this is a highly unlikely scenario in my opinion and experience. The trials were extensive enough to uncover any pattern of severe patient reaction (specifically allergic/anaphylactic). Since the post-approval death rate was 3 out of 25,000 patients, it seems much more likely the cause will be identified as "human error" at the dialysis site. In this case, we could anticipate the immediate return of OMONTYS,
Thanks for the article Jagan. I can't remember if someone had mentioned this before or if it was speculation but, were all the incidents concentrated in a few dialysis centers? It could be a possibility that it was a dialysis clinic that was re-branded with the Fresenius name after a buyout, however the safety protocols of the previous, presumably shoddy, clinic remained intact. It seems really far fetched but anything is worth examining to keep your money safe.
n this case, we could anticipate the immediate return of OMONTYS, with additional warning provisions and enhanced training requirements to be implemented and enforced at dialysis sites.
Patient issues unrelated to OMONTYS may be discovered as the cause or a significant contributing cause to the severe reactions and the 3 deaths.
New patients may have been given too high an initial dose. The severe reactions uniformly arose within 30 minutes of the first dose in new patients only.
The age and/or frailty of the patient may be a significant factor.
The severely affected patients may present with cancer and CKD, for which OMONTYS should Not have been prescribed.
Patients without a diagnosis of CKD may have received OMONTYS, which is Not indicated for these patients.
There may be other dosing factors. See the current dialysis issues involving dialysis products; namely GranuFlo and NaturaLyte. These dialysis solutions cannot be ruled out.
Severe reactions may have been inadequately handled by healthcare givers, or correct procedures may not have been followed, or there could have been contamination of the drug within the facility.
At this juncture, the future of Affymax all comes down to Takeda identifying and correcting the issue(s) with OMONTYS or the actual clinical administration of the drug itself. If it is in fact "human error" or dosing errors, the fix could be as simple as further warnings, a more specific "black box" warning, and/or additional training for dialysis personnel in the potential and remedies for such hyper-reactions, though they were fairly well documented when approved by the FDA.