Endotoxin content of Pfizer Multiple Myeloma Jab Elrexfio

Pfizer reported many cases of Myeloma after its Covid19 Jab and now wants to cash in on the increased market with another Cytokine Storm causing Jab

We know that Endotoxin and its Lipid A cause Myeloma.¹²

So does the Flagellin in Jabs.³

Now Pfizer has been given a rushed approval for its Elrexfio (Elranatamab) Jab⁴ claimed to help against Multiple Myeloma.⁵

Trouble is the product comes with boxed warning for Life-Threatening or Fatal Cytokine Release Syndrome and Neurologic Toxicity, including immune effector cell-associated neurotoxicity.

Other common side effects include:

• Fatigue

• Injection site reaction

• Diarrhea

• Upper respiratory tract infection

• Musculoskeletal Pain

• Pneumonia

• Decreased Appetite

• Rash

• Cough

• Nausea

• Pyrexia (Fever)

CTD references for Multiple Myeloma

I popped in to CTD to check out their huge reference collection for Multiple Myeloma.⁶

There they link Multiple Myeloma to thousands of chemicals, including Fluoride, that create Cytokine Storm. I have pulled out some of the more interesting papers regarding Endotoxin as a cause and will add more later.

CTD lists the following Genes dysregulated by Endotoxin in Multiple Myeloma:

BCL2 | BCL2L1 | BNIP3 | BTG1 | CCL2 | CCND1 | CD86 | CDKN2A | CSF2 | CSF3 | GSTT1 | HLA-A | HSPB1 | IFNA2 | IL6 | IRF4 | MCL1 | METTL14 | METTL3 | MUC1 | NQO1 | NUAK1 | PARP1 | PRAME | PRMT5 | SOD2 | SPARC | TNFSF8

Interleukins 1 and 6 are the main drivers.⁷⁸⁹¹⁰

Endotoxin in the Bone Marrow

Multiple myeloma cells express the CD180/MD-1 complex, a noncanonical Endotoxin receptor on their surface.¹¹

Mechanism involves TLR4

Endotoxin as readers kow only too well activates TLR4 and this protects Multiple Myeloma cells from apoptosis¹²¹³ by suppressing the CHOP-ATF4 branch.¹⁴

How much Endotoxin did FDA allow in Elrexfio ?

FDA did not know when they allowed marketing¹⁵, but of course knew that the large molecular weight of the product, formula C₆₄₄₀H₉₉₅₈N₁₇₃₈O₂₀₁₀S₄₉ 145,461.60 g·mol⁻¹ would make Low Endotoxin Recovery inevitable:

POSTMARKETING COMMITMENTS NOT SUBJECT TO THE REPORTING REQUIREMENTS UNDER SECTION 506B

We remind you of your postmarketing commitment:

4476-3 Conduct a Low Endotoxin Recovery (LER) study at process relevant temperature and duration to ensure that the bacterial endotoxins analytical method for release can reliably detect endotoxin in elranatamab drug product. In case the study shows endotoxin recoveries below 50% at process relevant conditions, develop an alternative endotoxin method to mitigate LER.

The timetable you submitted on August 8, 2023, states that you will conduct this study according to the following schedule:

Final Report Submission: 03/2024

Did Pfizer live up to this Endotoxin measurement commitment?

Please let me kow if you discover how much Endotoxin is in the Elrexfio Jab.

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4. https://en.wikipedia.org/wiki/Elranatamab

5. https://en.wikipedia.org/wiki/Multiple_myeloma

6. https://ctdbase.org/detail.go?acc=MESH%3AD009101&view=chem&sort=chemNmSort&page=59&type=disease&dir=asc

7. Z Y Lu, R Bataille, P Poubelle, M J Rapp, J L Harousseau, B Klein. 1995. An interleukin 1 receptor antagonist blocks the IL-1-induced IL-6 paracrine production through a prostaglandin E2-related mechanism in multiple myeloma. Stem Cells 1995 Aug:13 Suppl 2:28-34.

8. Min Yang, Jia-Kun Shen, Jian Huang, Hua-Ping Du, Qiu-Ling Ma, Jie Jin. 2009. Interleukin-6-independent expression of glucocorticoid receptor is upregulated by triptolide in multiple myeloma. https://www.tandfonline.com/doi/full/10.1080/10428190902801838

9. Dharminder Chauhan, Guilan Li, Teru Hideshima, Klaus Podar, Constantine Mitsiades, Nicholas Mitsiades, Laurence Catley, Yu Tzu Tai, Toshiaki Hayashi, Reshma Shringarpure, Renate Burger, Nikhil Munshi, Yasuyuki Ohtake, Satya Saxena, Kenneth C Anderson. 2003. Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance. https://ashpublications.org/blood/article/102/9/3379/17775/Hsp27-inhibits-release-of-mitochondrial-protein

10. Yang Xu, Yun Zhao, Haiwen Huang, Guanghua Chen, Xiaojin Wu, Ying Wang, Weirong Chang, Ziling Zhu, Yufeng Feng and Depei Wu. 2010. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2141.2010.08284.x

11. Jiro Kikuchi; Yoshiaki Kuroda; Daisuke Koyama; Naoki Osada; Tohru Izumi; Hiroshi Yasui; Takakazu Kawase; Tatsuo Ichinohe; Yusuke Furukawa. 2018. Myeloma Cells Are Activated in Bone Marrow Microenvironment by the CD180/MD-1 Complex, Which Senses Lipopolysaccharide. https://aacrjournals.org/cancerres/article/78/7/1766/633143/Myeloma-Cells-Are-Activated-in-Bone-Marrow

12. Hanying Bao, Peilin Lu, Yi Li, Lijuan Wang, Haiyan Li, Donghua He, Yang Yang, Yi Zhao, Li Yang, Micheal Wang, Qing Yi, Zhen Cai. 2011. Triggering of toll-like receptor-4 in human multiple myeloma cells promotes proliferation and alters cell responses to immune and chemotherapy drug attack. https://www.tandfonline.com/doi/abs/10.4161/cbt.11.1.13878

13. J Bohnhorst, T Rasmussen, SH Moen, M Fløttum, L Knudsen, M Børset, T Espevikand A Sundan. 2006. Toll-like receptors mediate proliferation and survival of multiple myeloma cells. https://www.nature.com/articles/2404225

14. Tina Bagratuni, Aimilia D Sklirou, Efstathios Kastritis, Christine Ivy Liacos, Christina Spilioti, Evangelos Eleutherakis-Papaiakovou, Nikolaos Kanellias, Maria Gavriatopoulou, Evangelos Terpos, Ioannis P Trougakos, Meletios A Dimopoulos. 2019. Toll-Like Receptor 4 Activation Promotes Multiple Myeloma Cell Growth and Survival Via Suppression of The Endoplasmic Reticulum Stress Factor Chop. https://www.nature.com/articles/s41598-019-39672-7

15. MARC R THEORET. 14 August 2023. FDA BLA ACCELERATED APPROVAL for Elrexfio (elranatamab-bcmm) injection.