Speculation On The Cause Of The OMONTYS Recall [View article]
Known as Hematide at the time of the clinicals, OMONTYS information at 2008 ASCO:
"With the use of Nektar's advanced PEGylation technology, the properties of therapeutic agents, such as Hematide(TM), can be enhanced by increasing drug circulation time in the bloodstream, decreasing immunogenicity, and reducing dosing frequency. Nektar proprietary technology uses advanced conjugation chemistry and techniques to attach polyethylene glycol polymers to therapeutic agents."
So, if PEG was of lower purity than actually stated (for example 90% instead of 98%), than the pegylation reaction wouldn't be efficient and yield 100% peginesatide. If that is the case, then let's say that about 5% of the peptidic ESA is still in the lower molecular weight form. If that is the case, there may be some induced immunogenicity which could possibly trigger the anaphylactic shock and other adverse events? See the following link about immunogenicity and anaphylactic shock: http://bit.ly/YMv8i2
In other words, excess PEG could be the culprit as could a shortage... Too much PEG left over in the final product could cause hypersensitivity while not enough could leave enough to leave lower molecular weight peptidic ESA unreacted which could induce immunogenicity and also trigger the AE's.
This is just conjecture and should not yet be construed as a "smoking gun".
Speculation On The Cause Of The OMONTYS Recall [View article]
Affymax 2010 10K statement pertaining to Nektar supply partnership for its PEG reagent: http://bit.ly/WOs5fz
"Under the agreement, we also engaged Nektar for the manufacture and supply of our requirements of bulk poly(ethylene) glycol reagent for the manufacture of peginesatide. This relationship is managed by a managing committee formed by representatives from both us and Nektar. Nektar is obligated to engage a third party manufacturer in the event of Nektar's failure (as defined in the agreement) to supply reagent, but currently Nektar remains our sole-source of these reagents.
This agreement expires, on a country by country basis, upon the expiration of our royalty payment obligations. The agreement may be terminated by either party for the other party's material breach provided that such other party has been given a chance to cure such breach, or by Nektar for our challenge of the validity or enforceability of any patents licensed thereunder."
Athersys' MultiStem Platform Tempts Big Pharma And Investors [View article]
Thanks wiesemc. I thought we might see some sort of pullback today due to warrants vote last Thursday. I will keep funds available to open a position if it does indeed drop. I may sell part of my substantial ACRX position tomorrow and move those funds over.
Speculation On The Cause Of The OMONTYS Recall [View article]
Great points all! The my goal with every piece I write is that my work is the BEGINNING of investors' due diligence. I hope for the patients' sakes and the investors experiencing the huge financial loss that everything works out well with OMONTYS.
Speculation On The Cause Of The OMONTYS Recall [View article]
The main point is that the compositions of the single use vials and the multiple use vials are different. If only one of the two types is determined to be at fault, the other type could potentially still be marketed.
Under "Adverse Reactions": "Allergic reactions have been reported in patients treated with OMONTYS. Discontinue OMONTYS and administer appropriate therapy if a serious allergic, anaphylactic or infusion-related reaction occurs."
Also of note pertaining to other possible allergens in the OMONTYS solution, there are no preservatives which eliminates those as being a potential concern in the single vials: "OMONTYS (peginesatide) Injection is formulated as a sterile, colorless to slightly yellow preservative-free solution and a sterile, colorless to slightly yellow preserved solution for intravenous or subcutaneous administration." Chemicals listed as part of the matrix in the single-use vials are noted on the label as "peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH. The pH is 6.0 ± 0.3."
For the multiple use injectable vials the matrix is a bit different as noted: "Multiple use, preserved injectable solutions of OMONTYS in vials are supplied in two fill volumes: 1 mL and 2 mL. Each mL contains 10 mg peginesatide, 47 mg sorbitol, 5 mg phenol, 1.5 mg L-methionine, 0.6 mg glacial acetic acid, and water for injection, USP. Sodium hydroxide added to adjust pH. The pH is 5.4 ± 0.5."
This brings up a VERY IMPORTANT point, let's suppose that only the single use vials or only the multiple use vials have been implicated with regard to the adverse events. If so, the implicated product type could be withdrawn from the market until an issue is found. Meanwhile, resumption of the other product's use/sales could continue?
Speculation On The Cause Of The OMONTYS Recall [View article]
Agreed Value. Nice points as well CS. It would be interesting to see if common "prick" tests or other means of evaluating for hypersensitivity would elicit a response (perhaps using one of the patients already having an adverse response).
I'll keep my eyes peeled for more updates. In terms of a "best case scenario", I hope for either a quick and easy means by which to eliminate the patient population that could be at risk or a simple resolution to the manufacturing issues, if there is one found.
3 Small Cap Radiopharmaceuticals With An Exciting 2013 Ahead [View article]
Without looking too deeply into it, the stock's illiquidity is an immediate red flag. Google shows its average trading volume at zero? Actually, I don't see a single trade made this year?
Imminent Catalysts Should Keep Investor Interest Alive For These Pharmaceuticals - Part II [View article]
I'm assuming you're referencing "With financing behind it, and solid phase 3 data in ARX-01 for a $6.0 billion market for post-operative pain"? That's not a reference to the market capitalization of ACRX but rather the total dollar value of all the drugs in the post-operative pain market. ARX-01 will be trying to get a piece of the $6.0 billion market. It remains to be seen how much of that market ARX-01 can take.
Pending Q4 Results: Dyax Partnerships Could Yield Sustained Growth For Investors [View article]
We'll know a bit more when Q4 results come out, but Q3 2012 total revenue was $13.1 million, $10.8 million of this was attributed to KALBITOR. However, I do agree that they have much potential revenue coming as KALBITOR progresses and royalties from Lilly and Amgen come into play. I hope to see exciting times ahead for Dyax, but it depends on how management handles marketing and its financials.
Speculation On The Cause Of The OMONTYS Recall [View article]
"With the use of Nektar's advanced PEGylation technology, the properties of therapeutic agents, such as Hematide(TM), can be enhanced by increasing drug circulation time in the bloodstream, decreasing immunogenicity, and reducing dosing frequency. Nektar proprietary technology uses advanced conjugation chemistry and techniques to attach polyethylene glycol polymers to therapeutic agents."
So, if PEG was of lower purity than actually stated (for example 90% instead of 98%), than the pegylation reaction wouldn't be efficient and yield 100% peginesatide. If that is the case, then let's say that about 5% of the peptidic ESA is still in the lower molecular weight form. If that is the case, there may be some induced immunogenicity which could possibly trigger the anaphylactic shock and other adverse events? See the following link about immunogenicity and anaphylactic shock: http://bit.ly/YMv8i2
In other words, excess PEG could be the culprit as could a shortage... Too much PEG left over in the final product could cause hypersensitivity while not enough could leave enough to leave lower molecular weight peptidic ESA unreacted which could induce immunogenicity and also trigger the AE's.
This is just conjecture and should not yet be construed as a "smoking gun".
Speculation On The Cause Of The OMONTYS Recall [View article]
http://bit.ly/WOs5fz
"Under the agreement, we also engaged Nektar for the manufacture and supply of our requirements of bulk poly(ethylene) glycol reagent for the manufacture of peginesatide. This relationship is managed by a managing committee formed by representatives from both us and Nektar. Nektar is obligated to engage a third party manufacturer in the event of Nektar's failure (as defined in the agreement) to supply reagent, but currently Nektar remains our sole-source of these reagents.
This agreement expires, on a country by country basis, upon the expiration of our royalty payment obligations. The agreement may be terminated by either party for the other party's material breach provided that such other party has been given a chance to cure such breach, or by Nektar for our challenge of the validity or enforceability of any patents licensed thereunder."
Speculation On The Cause Of The OMONTYS Recall [View article]
"Nektar
Affymax has an agreement with Nektar which covers Nektar’s supply of PEG (polyethylene glycol) to Affymax for the production of peginesatide."
Still digging deeper..
Athersys' MultiStem Platform Tempts Big Pharma And Investors [View article]
ACRX news out after hours today:
http://bit.ly/XT1QPL;highlight=
By the way, thanks for above... :)
Athersys' MultiStem Platform Tempts Big Pharma And Investors [View article]
CF
Speculation On The Cause Of The OMONTYS Recall [View article]
CF
Speculation On The Cause Of The OMONTYS Recall [View article]
Speculation On The Cause Of The OMONTYS Recall [View article]
Speculation On The Cause Of The OMONTYS Recall [View article]
http://1.usa.gov/VRjpSs
Under "Adverse Reactions":
"Allergic reactions have been reported in patients treated with OMONTYS. Discontinue OMONTYS and administer appropriate therapy if a serious allergic, anaphylactic or infusion-related reaction occurs."
Also of note pertaining to other possible allergens in the OMONTYS solution, there are no preservatives which eliminates those as being a potential concern in the single vials:
"OMONTYS (peginesatide) Injection is formulated as a sterile, colorless to slightly yellow preservative-free solution and a sterile, colorless to slightly yellow preserved solution for intravenous or subcutaneous administration."
Chemicals listed as part of the matrix in the single-use vials are noted on the label as "peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH. The pH is 6.0 ± 0.3."
For the multiple use injectable vials the matrix is a bit different as noted: "Multiple use, preserved injectable solutions of OMONTYS in vials are supplied in two fill volumes: 1 mL and 2 mL. Each mL contains 10 mg peginesatide, 47 mg sorbitol, 5 mg phenol,
1.5 mg L-methionine, 0.6 mg glacial acetic acid, and water for injection, USP. Sodium hydroxide added to adjust pH. The pH is 5.4 ± 0.5."
This brings up a VERY IMPORTANT point, let's suppose that only the single use vials or only the multiple use vials have been implicated with regard to the adverse events. If so, the implicated product type could be withdrawn from the market until an issue is found. Meanwhile, resumption of the other product's use/sales could continue?
Speculation On The Cause Of The OMONTYS Recall [View article]
I'll keep my eyes peeled for more updates. In terms of a "best case scenario", I hope for either a quick and easy means by which to eliminate the patient population that could be at risk or a simple resolution to the manufacturing issues, if there is one found.
3 Small Cap Radiopharmaceuticals With An Exciting 2013 Ahead [View article]
Imminent Catalysts Should Keep Investor Interest Alive For These Pharmaceuticals - Part II [View article]
Thanks and hope your week is going well.
Small Pharmaceuticals With Near Term Catalysts Offer Investment Opportunities [View article]
Good luck in the year ahead.
3 Small Cap Radiopharmaceuticals With An Exciting 2013 Ahead [View article]
Another weapon in the fight against cancer... as I hope radiogel and Y-90 clivatuzumab could some day also be approved...
Pending Q4 Results: Dyax Partnerships Could Yield Sustained Growth For Investors [View article]