Here may a clue about the prioritizing of a trial for MSS CRC from todays letter.
“…The prospective clinical trials, in order of priority, are: (i) a Phase II study of leronlimab in patients with relapsed/refractory microsatellite stable colorectal cancer; and … The Company’s priority will be the oncology trial which, if successful, will put us on track towards a commercial approval of leronlimab in that indication…
I took a look at the two drugs mentioned in Plotinus’s link to the 5/7/24 MSS CRC paper. They were used in combo with chemotherapy and checkpoint inhibitors.
I’ll link a Wikipedia link to the two ‘approved with chemo’ drugs mentioned in Plot’s link…Cetuximab, and Bevacizumab, are owned by Sanofi-Aventis and Fenentech, respectively. Maravoric was also explored as a CCR5 inhibitor for the study. And anything Mavavoric can do we can do better (no link to Gilead required).
https://en.wikipedia.org/wiki/Cetuximab
https://en.wikipedia.org/wiki/Bevacizumab
“Cetuximab, sold under the brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor medication used for the treatment of metastatic colorectal cancer and head and neck cancer.[2] Cetuximab is a chimeric (mouse/human) monoclonal antibody given by intravenous infusion.[2]”
“In July 2009, the U.S. Food and Drug Administration (FDA) approved cetuximab (Erbitux) for treatment of colon cancer with wild-type KRAS, since it had little or no effect in colorectal tumors harboring a KRAS mutation (this also applied to the EGFR antibody panitumumab).[4] This was the first genetic test to guide treatment of cancer.[5] In July 2012, the FDA approved a real time PCR companion diagnostic test for KRAS, the therascreen KRAS test.[6]”
….”for the use of anti-epidermal growth factor receptor antibodies in combination with chemotherapy, to slow the growth of certain tumors which was filed in 1989 by Rhone-Poulenc-Rorer.[24] The court ruled that Yeda is sole owner of the patent in the U.S., while Yeda and Sanofi-Aventis co-own the patent's foreign counterparts.[25][26][27]”
Side effects
edit
One of the more serious side effects of cetuximab therapy is the incidence of acne-like rash. This rash rarely leads to dose reductions or termination of therapy. It is generally reversible.[12]
Further severe infusion reactions include but are not limited to: fevers, chills, rigors, urticaria, itchiness, rash, hypotension, nausea, vomiting, headache, shortness of breath, wheezing, angioedema, dizziness, anaphylaxis, and cardiac arrest. Other common side effects include photosensitivity, hypomagnesemia due to magnesium wasting, and less commonly pulmonary and cardiac toxicity.[13]
Alpha-gal allergy
edit
Certain geographic regions have a high rate of anaphylactic reactions to cetuximab upon the first exposure to the medication. This is unusual because exposure to the allergen must occur before the development of an allergy. Fewer than 1% of people in the northeast United States reacted, while greater than 20% in the southeast did.[14][15]”
And further…the other approved combo drug…
“Bevacizumab was approved for medical use in the United States in 2004.[30][28] It is on the World Health Organization's List of Essential Medicines[31][32][33] It is listed for its use in treating eye disease.[31][32]”
“Common side effects when used for cancer include nose bleeds, headache, high blood pressure, and rash.[28] Other severe side effects include gastrointestinal perforation, bleeding, allergic reactions, blood clots, and an increased risk of infection.[28] When used for eye disease side effects can include vision loss and retinal detachment.[28] Bevacizumab is a monoclonal antibody that functions as an angiogenesis inhibitor.[28] It works by slowing the growth of new blood vessels by inhibiting vascular endothelial growth factor A (VEGF-A), in other words anti–VEGF therapy.[28]”
“Approval
edit
It received its first approval in the United States in 2004, for combination use with standard chemotherapy for metastatic colon cancer.[71] It has since been approved for use in certain lung cancers, renal cancers, ovarian cancers, and glioblastoma multiforme of the brain.[medical citation needed]
In 2008, bevacizumab was approved for breast cancer by the FDA, but the approval was revoked on 18 November 2011[80][81][82] because, although there was evidence that it slowed progression of metastatic breast cancer, there was no evidence that it extended life or improved quality of life, and it caused adverse effects including severe high blood pressure and hemorrhaging.[medical citation needed]
In 2008, the FDA gave bevacizumab provisional approval for metastatic breast cancer, subject to further studies. The FDA's advisory panel had recommended against approval.[83] In July 2010, after new studies failed to show a significant benefit, the FDA's advisory panel recommended against the indication for advanced breast cancer. Genentech requested a hearing, which was granted in June 2011. The FDA ruled to withdraw the breast cancer indication in November 2011. FDA approval is required for Genentech to market a drug for that indication. Doctors may sometimes prescribe it for that indication, although insurance companies are less likely to pay for it.[81]”
So my theory is, the reason Dr J is prioritizing the MSS CRC trial is that two approved drugs are not as good at inhibiting CCR5, and Maravoric is showing promise for approval here. And we can do better?
So could be easy-ish to steal the ball from Gilead, and Sandi and Genentech will both be tipping the cap.
“…The prospective clinical trials, in order of priority, are: (i) a Phase II study of leronlimab in patients with relapsed/refractory microsatellite stable colorectal cancer; and … The Company’s priority will be the oncology trial which, if successful, will put us on track towards a commercial approval of leronlimab in that indication…
I took a look at the two drugs mentioned in Plotinus’s link to the 5/7/24 MSS CRC paper. They were used in combo with chemotherapy and checkpoint inhibitors.
I’ll link a Wikipedia link to the two ‘approved with chemo’ drugs mentioned in Plot’s link…Cetuximab, and Bevacizumab, are owned by Sanofi-Aventis and Fenentech, respectively. Maravoric was also explored as a CCR5 inhibitor for the study. And anything Mavavoric can do we can do better (no link to Gilead required).
https://en.wikipedia.org/wiki/Cetuximab
https://en.wikipedia.org/wiki/Bevacizumab
“Cetuximab, sold under the brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor medication used for the treatment of metastatic colorectal cancer and head and neck cancer.[2] Cetuximab is a chimeric (mouse/human) monoclonal antibody given by intravenous infusion.[2]”
“In July 2009, the U.S. Food and Drug Administration (FDA) approved cetuximab (Erbitux) for treatment of colon cancer with wild-type KRAS, since it had little or no effect in colorectal tumors harboring a KRAS mutation (this also applied to the EGFR antibody panitumumab).[4] This was the first genetic test to guide treatment of cancer.[5] In July 2012, the FDA approved a real time PCR companion diagnostic test for KRAS, the therascreen KRAS test.[6]”
….”for the use of anti-epidermal growth factor receptor antibodies in combination with chemotherapy, to slow the growth of certain tumors which was filed in 1989 by Rhone-Poulenc-Rorer.[24] The court ruled that Yeda is sole owner of the patent in the U.S., while Yeda and Sanofi-Aventis co-own the patent's foreign counterparts.[25][26][27]”
Side effects
edit
One of the more serious side effects of cetuximab therapy is the incidence of acne-like rash. This rash rarely leads to dose reductions or termination of therapy. It is generally reversible.[12]
Further severe infusion reactions include but are not limited to: fevers, chills, rigors, urticaria, itchiness, rash, hypotension, nausea, vomiting, headache, shortness of breath, wheezing, angioedema, dizziness, anaphylaxis, and cardiac arrest. Other common side effects include photosensitivity, hypomagnesemia due to magnesium wasting, and less commonly pulmonary and cardiac toxicity.[13]
Alpha-gal allergy
edit
Certain geographic regions have a high rate of anaphylactic reactions to cetuximab upon the first exposure to the medication. This is unusual because exposure to the allergen must occur before the development of an allergy. Fewer than 1% of people in the northeast United States reacted, while greater than 20% in the southeast did.[14][15]”
And further…the other approved combo drug…
“Bevacizumab was approved for medical use in the United States in 2004.[30][28] It is on the World Health Organization's List of Essential Medicines[31][32][33] It is listed for its use in treating eye disease.[31][32]”
“Common side effects when used for cancer include nose bleeds, headache, high blood pressure, and rash.[28] Other severe side effects include gastrointestinal perforation, bleeding, allergic reactions, blood clots, and an increased risk of infection.[28] When used for eye disease side effects can include vision loss and retinal detachment.[28] Bevacizumab is a monoclonal antibody that functions as an angiogenesis inhibitor.[28] It works by slowing the growth of new blood vessels by inhibiting vascular endothelial growth factor A (VEGF-A), in other words anti–VEGF therapy.[28]”
“Approval
edit
It received its first approval in the United States in 2004, for combination use with standard chemotherapy for metastatic colon cancer.[71] It has since been approved for use in certain lung cancers, renal cancers, ovarian cancers, and glioblastoma multiforme of the brain.[medical citation needed]
In 2008, bevacizumab was approved for breast cancer by the FDA, but the approval was revoked on 18 November 2011[80][81][82] because, although there was evidence that it slowed progression of metastatic breast cancer, there was no evidence that it extended life or improved quality of life, and it caused adverse effects including severe high blood pressure and hemorrhaging.[medical citation needed]
In 2008, the FDA gave bevacizumab provisional approval for metastatic breast cancer, subject to further studies. The FDA's advisory panel had recommended against approval.[83] In July 2010, after new studies failed to show a significant benefit, the FDA's advisory panel recommended against the indication for advanced breast cancer. Genentech requested a hearing, which was granted in June 2011. The FDA ruled to withdraw the breast cancer indication in November 2011. FDA approval is required for Genentech to market a drug for that indication. Doctors may sometimes prescribe it for that indication, although insurance companies are less likely to pay for it.[81]”
So my theory is, the reason Dr J is prioritizing the MSS CRC trial is that two approved drugs are not as good at inhibiting CCR5, and Maravoric is showing promise for approval here. And we can do better?
So could be easy-ish to steal the ball from Gilead, and Sandi and Genentech will both be tipping the cap.
12
