AMG 420 - Amgen
In my previous post about BB2121, I noted that AMG 420 seemed more effective scientifically, and more practical from a cost point of view as compared to BB2121. I decided to explore that a bit further.
The Science
AMG 420 is an anti-BCMA x anti-CD3 BiTE (Bi-specific T cell engager) antibody construct currently being investigated as a treatment for multiple myeloma by Amgen.
Multiple myeloma is a cancer that originates in plasma cells, a type of white blood cell. It can impact much of the body but especially target the bone marrow where plasma cells are made. Multiple myeloma cells produce a protein called B-cell maturation antigen (BCMA) in excess.
The immune system usually can recognise abnormal cells, such as cancer cells, and uses specific immune cells, such as T-cells, to destroy them. However, some tumour cells develop mechanisms to evade detection by the immune system.
AMG 420 is an immunotherapy, meaning that it does not directly target the tumour but aims to direct the body’s own immune system to attack cells producing a certain protein. It is made using Amgen’s proprietary BiTE or “bi-specific T-cell engager” technology. AMG 420 consists of two proteins fused together, each designed to interact with a specific target — in this case, BCMA on tumour cells and CD3, a protein found on the surface of T-cells.
By binding simultaneously to BCMA on the tumour cell and CD3 on T-cells, AMG 420 forms a bridge between the T-cell and the tumour cell. This allows the T-cell to be able to recognise and target the tumour cell, with the intent of halting cancer progression and reducing tumour size.
The Upside
The therapy is currently focused on Multiple Myeloma, with potential in Acute Myeloid Leukaemia. Currently it has only been investigated in a Phase I dose escalation study, meaning it is still very early doors, but 66.5% of Phase I trials pass to Phase II.
In the study 42 patients who had cancer progression after two prior lines of treatment were give AMG 420 at varying doses (0.2 to 800 micrograms). The 400 microgram dose was shown to be the most effective. At this dose the response rate was 83% and 5/5 patients achieved minimal residual disease (MRD) negative complete responses, meaning no cancer cells were found in the bone marrow.
These first-in-human data of a BCMA-targeting BiTE® immunotherapy showed encouraging evidence of AMG 420 activity, with no major toxicities up to the 400 microgram dose in patients with relapsed and/or refractory multiple myeloma who received a median of four prior therapies.
Additionally, AMG 420 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA). Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions.
This treatment is hard to compare to anything on the market at the moment as the BiTE mechanism is unique. But just to give some context, another study involving a BiTE therapy developed by Amgen that targets CD33, showed MRD negative complete responses in 20% of patients and nowhere near the same response rate. Meaning AMG 420's mechanism of targeting BCMA is actually quite special.
AMG 420 is given intravenously in cycles lasting 6 weeks (4 weeks on, 2 weeks off), this is continued for up to 5 cycles or until disease progression, toxicity or a new therapy is started.
The estimated worldwide 5 year prevalence (patients diagnosed within the last 5 years) of patients with multiple myeloma is roughly 230,000, with around 30,000 new cases diagnosed each year.
Amgen has a marketed BiTE Immunotherapy called Blincyto that costs $89,000 a cycle. Lets make the assumption AMG 420 will cost the same amount as Blincyto. If we take this figure and multiply it by 5.3 for the 5.3 cycles required (responders were treated for a mean (SD) of 5.3 (3.3) cycles) we get $471,700 dollars for a response.
Lets say patients relapsed twice over 2 years before they became eligible for AMG 420. This would mean 60% of the 230,000 patients were eligible at 138,000 patients.
But of course, AMG 420 would not command the full market share, especially with Revlimid and Pomalyst currently out there, not to mention if BB2121 gains approval. Say 10% of these eligible patients are treated, that would be 13,800 patients. At $471,700 dollars per patient, that could mean $6,509,460,000 in sales each year, making AMG 420 a blockbuster drug.
Looking at data for Amgen from 30th Sept 2018. The Sales per Share value was $33.98. At 649 Million shares, this means sales were roughly $22 Billion, about right looking at the balance sheets. If we add an extra $6.5 Billion to this and then divide by the $649 Million shares outstanding, we get a sales per share value of $43.99. Now the Price to Sales ratio for the same period was 6.10. Taking our Sales per Share and our Price to Sales ratio we get a rough stock price of $267. A $60 (30%) premium to the stock price on 30th Sept 2018.
Please be reminded these calculations are extremely crude and hypothetical!
AMG 420 is still in Phase I trials, the likelihood of final approval of a therapy as it passes Phase I trials is 15.3%. AMG 420 still has a very long way to go. With results like AMG 420's, it will pass into Phase II, however Phase II is the most limiting Phase with only 39.5% of therapies passing into Phase III.
AMG 420 currently has a lot of competition in the Multiple Myeloma market. Celgene has 2 marketed treatments Revlimid and Pomalyst, not to mention the collaboration treatment with Bluebird Bio, BB2121.
The dosing schedule of AMG 420 is anything but convenient for the patient. It consists of a continuous 4 week infusion over 4 weeks, and that is only one cycle. CAR-T products like BB2121 need to be infused only once. Granted, the cost of CAR-T therapy may be a little higher as the patients T-Cells must be extracted, genetically modified and re introduced, but this single dose is a clear competitive advantage. Amgen are however working on a once-weekly formulation, efficacy and safety data will have to be generated before it is approved.
Looking at FDA approved BiTE and CAR-T products as comparisons, Blincyto and Kymriah respectively. CAR-T products generally produce more efficacious response rates and longer durations of response. These treatments do target a different receptor, CD19, so do not serve as the most accurate comparison. However, the differences between BiTE and CAR-T are stark and this could imply which is a more effective treatment.
At the moment, I feel it is too early to really justify my opinion on AMG 420. The therapy has a very long way to go. I can't wait to see Phase I and subsequent Phase II results for AMG 420 and I may consider revisiting it after those are announced.
I believe the off-the-shelf availability of AMG 420 is a huge positive in the world of Immunotherapy. CAR-T therapies command a huge price due to the individualistic nature of them. AMG 420 would not have quite such a high price tag as it can be mass produced and given to any patient with Multiple Myeloma. This could mean Hospitals may choose to preferably adopt it over BB2121 if they are lacking the finances or facilities to produce a CAR-T therapy. Admittedly CAR-T's only have to be infused once, which is a huge pro. But if Amgen really is working on a once-weekly BiTE formulation, I would have high hopes for it in the future.
-OC
Disclaimer:
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it. I have no business relationship with any company who is mentioned in this article. This article is not investment advice, and can't be relied upon by anyone for any reason except, arguably, entertainment purposes. I am not an investment advisor.
In the study 42 patients who had cancer progression after two prior lines of treatment were give AMG 420 at varying doses (0.2 to 800 micrograms). The 400 microgram dose was shown to be the most effective. At this dose the response rate was 83% and 5/5 patients achieved minimal residual disease (MRD) negative complete responses, meaning no cancer cells were found in the bone marrow.
These first-in-human data of a BCMA-targeting BiTE® immunotherapy showed encouraging evidence of AMG 420 activity, with no major toxicities up to the 400 microgram dose in patients with relapsed and/or refractory multiple myeloma who received a median of four prior therapies.
Additionally, AMG 420 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA). Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions.
This treatment is hard to compare to anything on the market at the moment as the BiTE mechanism is unique. But just to give some context, another study involving a BiTE therapy developed by Amgen that targets CD33, showed MRD negative complete responses in 20% of patients and nowhere near the same response rate. Meaning AMG 420's mechanism of targeting BCMA is actually quite special.
AMG 420 is given intravenously in cycles lasting 6 weeks (4 weeks on, 2 weeks off), this is continued for up to 5 cycles or until disease progression, toxicity or a new therapy is started.
The estimated worldwide 5 year prevalence (patients diagnosed within the last 5 years) of patients with multiple myeloma is roughly 230,000, with around 30,000 new cases diagnosed each year.
Amgen has a marketed BiTE Immunotherapy called Blincyto that costs $89,000 a cycle. Lets make the assumption AMG 420 will cost the same amount as Blincyto. If we take this figure and multiply it by 5.3 for the 5.3 cycles required (responders were treated for a mean (SD) of 5.3 (3.3) cycles) we get $471,700 dollars for a response.
Lets say patients relapsed twice over 2 years before they became eligible for AMG 420. This would mean 60% of the 230,000 patients were eligible at 138,000 patients.
But of course, AMG 420 would not command the full market share, especially with Revlimid and Pomalyst currently out there, not to mention if BB2121 gains approval. Say 10% of these eligible patients are treated, that would be 13,800 patients. At $471,700 dollars per patient, that could mean $6,509,460,000 in sales each year, making AMG 420 a blockbuster drug.
Looking at data for Amgen from 30th Sept 2018. The Sales per Share value was $33.98. At 649 Million shares, this means sales were roughly $22 Billion, about right looking at the balance sheets. If we add an extra $6.5 Billion to this and then divide by the $649 Million shares outstanding, we get a sales per share value of $43.99. Now the Price to Sales ratio for the same period was 6.10. Taking our Sales per Share and our Price to Sales ratio we get a rough stock price of $267. A $60 (30%) premium to the stock price on 30th Sept 2018.
Please be reminded these calculations are extremely crude and hypothetical!
The Downside
AMG 420 is still in Phase I trials, the likelihood of final approval of a therapy as it passes Phase I trials is 15.3%. AMG 420 still has a very long way to go. With results like AMG 420's, it will pass into Phase II, however Phase II is the most limiting Phase with only 39.5% of therapies passing into Phase III.
The dosing schedule of AMG 420 is anything but convenient for the patient. It consists of a continuous 4 week infusion over 4 weeks, and that is only one cycle. CAR-T products like BB2121 need to be infused only once. Granted, the cost of CAR-T therapy may be a little higher as the patients T-Cells must be extracted, genetically modified and re introduced, but this single dose is a clear competitive advantage. Amgen are however working on a once-weekly formulation, efficacy and safety data will have to be generated before it is approved.
Looking at FDA approved BiTE and CAR-T products as comparisons, Blincyto and Kymriah respectively. CAR-T products generally produce more efficacious response rates and longer durations of response. These treatments do target a different receptor, CD19, so do not serve as the most accurate comparison. However, the differences between BiTE and CAR-T are stark and this could imply which is a more effective treatment.
The Conclusion
I believe the off-the-shelf availability of AMG 420 is a huge positive in the world of Immunotherapy. CAR-T therapies command a huge price due to the individualistic nature of them. AMG 420 would not have quite such a high price tag as it can be mass produced and given to any patient with Multiple Myeloma. This could mean Hospitals may choose to preferably adopt it over BB2121 if they are lacking the finances or facilities to produce a CAR-T therapy. Admittedly CAR-T's only have to be infused once, which is a huge pro. But if Amgen really is working on a once-weekly BiTE formulation, I would have high hopes for it in the future.
-OC
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it. I have no business relationship with any company who is mentioned in this article. This article is not investment advice, and can't be relied upon by anyone for any reason except, arguably, entertainment purposes. I am not an investment advisor.
Comments
Post a Comment