Came across this in a news article:
"Daratumumab is given once a week for the first two months of treatment, then the infusions wind down to once monthly in the second 6 months of the year, says a spokesperson for J&J. For the first full year--with a total of 23 doses given at a cost of $5,850 per infusion--the average monthly wholesale acquisition cost is $11,212, says J&J, or $135,550 for the first year. In year two, and any year thereafter, patients receive a total of 13 doses, for a monthly wholesale cost of $6,337, or $76,044 annually. J&J also offers programs to limit patient's out-of-pocket costs and will be offering payers discounts during price negotiations."
Forums
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cdnirene - Name: Irene S
- Who do you know with myeloma?: me
- When were you/they diagnosed?: September 2014
- Age at diagnosis: 66
Re: FDA approves Darzalex (daratumumab)
Irene,
From what I have seen, Johnson & Johnson apparently worked really hard to get out a specific message about the price of Darzalex. They want everyone to focus on the cost per year. You see it as the focus in just about every article about the drug's approval.
There's a reason for this. The yearly cost of Darzalex is more comparable to the yearly cost of other myeloma drugs. More importantly, focusing on the yearly cost makes the initial cost of the drug – $23,000 per month for the first two months – seem more palatable.
But it's also borderline ridiculous to focus, at this point, on the yearly cost of the drug. In the APPROVED patient population, 40 or 50 percent of patients won't even respond to the drug. So they will get at most a month or two of the drug at the initial price of $23,000 per month.
For those patients who do respond to the drug, the median duration of response is, what, maybe 7 or 8 months (again, focusing on the APPROVED patient population)? So, even among the patients who respond, only a few are going to be treated for a year.
To be honest, if I were the FDA, I would be looking very closely at what J&J is communicating about the pricing of the drug. True, the FDA has no authority over drug pricing. However, it does have authority about what a company's marketing and publicity activities say, or imply, about the appropriate use of the drug.
And, right now, J&J is implying through its communication about Darzalex pricing that patients may commonly be treated with the drug for a year or more. There is nothing in the approved prescribing information for the drug that suggests that will regularly be the case.
From what I have seen, Johnson & Johnson apparently worked really hard to get out a specific message about the price of Darzalex. They want everyone to focus on the cost per year. You see it as the focus in just about every article about the drug's approval.
There's a reason for this. The yearly cost of Darzalex is more comparable to the yearly cost of other myeloma drugs. More importantly, focusing on the yearly cost makes the initial cost of the drug – $23,000 per month for the first two months – seem more palatable.
But it's also borderline ridiculous to focus, at this point, on the yearly cost of the drug. In the APPROVED patient population, 40 or 50 percent of patients won't even respond to the drug. So they will get at most a month or two of the drug at the initial price of $23,000 per month.
For those patients who do respond to the drug, the median duration of response is, what, maybe 7 or 8 months (again, focusing on the APPROVED patient population)? So, even among the patients who respond, only a few are going to be treated for a year.
To be honest, if I were the FDA, I would be looking very closely at what J&J is communicating about the pricing of the drug. True, the FDA has no authority over drug pricing. However, it does have authority about what a company's marketing and publicity activities say, or imply, about the appropriate use of the drug.
And, right now, J&J is implying through its communication about Darzalex pricing that patients may commonly be treated with the drug for a year or more. There is nothing in the approved prescribing information for the drug that suggests that will regularly be the case.
Re: FDA approves Darzalex (daratumumab)
New study results for dara with Revlimid was just released. Pretty encouraging results, IMHO.
http://www.prnewswire.com/news-releases/daratumumab-darzalex-combined-with-standard-treatment-for-multiple-myeloma-produced-deep-and-durable-responses-in-relapsed-or-refractory-patients-300188611.html
"....Janssen Research & Development, LLC announced new data from the ongoing Phase 1/2 GEN503 investigational study showing the human CD38-directed monoclonal antibody daratumumab (DARZALEX™), in combination with lenalidomide and dexamethasone, yielded an overall response rate (ORR) of 81 percent in relapsed or refractory multiple myeloma patients who had received a median of two prior therapies. After 18 months of treatment, investigators observed an overall survival (OS) rate of 90 percent, with 72 percent of patients experiencing progression-free survival (PFS).1 The data, from the part 2 cohort expansion phase of GEN503, were presented today during the official press program at the 57th Annual American Society of Hematology (ASH) Meeting and Exposition in Orlando, FL and will be presented in full during an oral abstract session on Monday, December 7 at 7:30 a.m. Eastern Time (ET)".
http://www.prnewswire.com/news-releases/daratumumab-darzalex-combined-with-standard-treatment-for-multiple-myeloma-produced-deep-and-durable-responses-in-relapsed-or-refractory-patients-300188611.html
"....Janssen Research & Development, LLC announced new data from the ongoing Phase 1/2 GEN503 investigational study showing the human CD38-directed monoclonal antibody daratumumab (DARZALEX™), in combination with lenalidomide and dexamethasone, yielded an overall response rate (ORR) of 81 percent in relapsed or refractory multiple myeloma patients who had received a median of two prior therapies. After 18 months of treatment, investigators observed an overall survival (OS) rate of 90 percent, with 72 percent of patients experiencing progression-free survival (PFS).1 The data, from the part 2 cohort expansion phase of GEN503, were presented today during the official press program at the 57th Annual American Society of Hematology (ASH) Meeting and Exposition in Orlando, FL and will be presented in full during an oral abstract session on Monday, December 7 at 7:30 a.m. Eastern Time (ET)".
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: FDA approves Darzalex (daratumumab)
Wow! Correct me if I'm wrong, but 72% PFS after 18 months sounds unprecedented in the relapsed/refractory population.
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Mike F - Name: Mike F
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: May 18, 2012
- Age at diagnosis: 53
Re: FDA approves Darzalex (daratumumab)
This is not an all that difficult to treat study population and would be applicable to few myeloma relapsed patients here in the US. Note two thirds had never received prior Revlimid.
"The study design of this ongoing, open-label phase 1/2 study of DARA in combination with LEN/DEX has been presented previously (Plesner T. Blood2014;124(21):84). Briefly, the study comprised a 3 + 3 design dose escalation study (DARA 2-16 mg/kg + LEN/DEX; Part 1) and a cohort expansion study using the recommended phase 2 dose (DARA 16 mg/kg + LEN/DEX; Part 2). In Part 2, patients refractory to LEN were excluded and patients with ≥1 prior line of therapy were included."
"The median (range) number of prior lines of therapy was 2 (1-3) and the median (range) duration of follow up was 7.8 (3.0-10.4) months. Eleven (34%) patients received prior LEN treatment. Six (19%) patients discontinued treatment due to either disease progression (n = 3), treatment-emergent adverse events (TEAE; 1 patient with gastric adenocarcinoma and 1 patient with laryngeal edema that was a grade 3 infusion-related reaction [IRR]), or physician decision (n = 1)."
https://myelomabeacon.org/resources/mtgs/ash2015/abs/507/
Also note that Revlimid was dosed at 25 mg in this study. Based on what I read, patients find it difficult to tolerate that dose for long periods. I have never needed Revlimid so I have no personal experience with the side effects. Is 40 mg a typically well tolerated dose of DEX? I have not used DEX for 5 years so I am not sure if that is a well tolerated dose or not with regard to long term use. These side effects may be mostly from the Revlimid and DEX, but 50% experienced a serious side effect. Also not noted is the "time toxicity" to the patient - they have to go to the clinic to get DARA.
"According to the results, there were no new safety signals identified when daratumumab was given in combination with lenalidomide/dexamethasone. Only three of 32 patients had to discontinue treatment due to adverse events.The most common adverse events were neutropenia (84%), cough (50%), diarrhea (44%), and muscle spasms (44%). Although half of the patients experienced a serious adverse event, only neutropenia, gastroenteritis, and pyrexia occurred in more than one patient.
http://www.cancernetwork.com/ash-2015/daratumumab-combo-safe-durable-relapsedrefractory-myeloma
In my opinion, quality of life should be important when looking at treatment statistics. Also note the primary endpoint of this study was safety as opposed to treatment efficiency. It clearly hit the primary endpoint of the study. They have randomized trials going on to compare DARA/REV/DEX to REV/DEX to show the added benefit of DARA.
I think DARA will likely join proteasome inhibitors, IMIDs and high dose melphalan as the most important therapies for myeloma patients. The study that got it approved was clearly more impressive in my opinion than this study as DARA demonstrated single agent activity in a more heavily pre-treated population than this study shows.
"The study design of this ongoing, open-label phase 1/2 study of DARA in combination with LEN/DEX has been presented previously (Plesner T. Blood2014;124(21):84). Briefly, the study comprised a 3 + 3 design dose escalation study (DARA 2-16 mg/kg + LEN/DEX; Part 1) and a cohort expansion study using the recommended phase 2 dose (DARA 16 mg/kg + LEN/DEX; Part 2). In Part 2, patients refractory to LEN were excluded and patients with ≥1 prior line of therapy were included."
"The median (range) number of prior lines of therapy was 2 (1-3) and the median (range) duration of follow up was 7.8 (3.0-10.4) months. Eleven (34%) patients received prior LEN treatment. Six (19%) patients discontinued treatment due to either disease progression (n = 3), treatment-emergent adverse events (TEAE; 1 patient with gastric adenocarcinoma and 1 patient with laryngeal edema that was a grade 3 infusion-related reaction [IRR]), or physician decision (n = 1)."
https://myelomabeacon.org/resources/mtgs/ash2015/abs/507/
Also note that Revlimid was dosed at 25 mg in this study. Based on what I read, patients find it difficult to tolerate that dose for long periods. I have never needed Revlimid so I have no personal experience with the side effects. Is 40 mg a typically well tolerated dose of DEX? I have not used DEX for 5 years so I am not sure if that is a well tolerated dose or not with regard to long term use. These side effects may be mostly from the Revlimid and DEX, but 50% experienced a serious side effect. Also not noted is the "time toxicity" to the patient - they have to go to the clinic to get DARA.
"According to the results, there were no new safety signals identified when daratumumab was given in combination with lenalidomide/dexamethasone. Only three of 32 patients had to discontinue treatment due to adverse events.The most common adverse events were neutropenia (84%), cough (50%), diarrhea (44%), and muscle spasms (44%). Although half of the patients experienced a serious adverse event, only neutropenia, gastroenteritis, and pyrexia occurred in more than one patient.
http://www.cancernetwork.com/ash-2015/daratumumab-combo-safe-durable-relapsedrefractory-myeloma
In my opinion, quality of life should be important when looking at treatment statistics. Also note the primary endpoint of this study was safety as opposed to treatment efficiency. It clearly hit the primary endpoint of the study. They have randomized trials going on to compare DARA/REV/DEX to REV/DEX to show the added benefit of DARA.
I think DARA will likely join proteasome inhibitors, IMIDs and high dose melphalan as the most important therapies for myeloma patients. The study that got it approved was clearly more impressive in my opinion than this study as DARA demonstrated single agent activity in a more heavily pre-treated population than this study shows.
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Mark11
Re: FDA approves Darzalex (daratumumab)
Good analysis, Marc. Thanks for that.
Certainly agree that quality of life is an essential aspect of any of this.
Certainly agree that quality of life is an essential aspect of any of this.
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Mike F - Name: Mike F
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: May 18, 2012
- Age at diagnosis: 53
Re: FDA approves Darzalex (daratumumab)
I was trying to find the info, but what concerned me is there are patients on this getting blood transfusions twice a week. Also, 10% chance of secondary hard tumor cancers? I would not want to deal with that. I am scared of this drug. Am I wrong to be concerned?
Re: FDA approves Darzalex (daratumumab)
Hi Dee,
All myeloma therapies can have significant side effects. Myeloma patients are more apt to be getting blood transfusions than the general population. Do not forget that most of the studies on daratumumab are on relapsed patients, so some of the need for blood transfusions could partially be due to the cumulative toxicity of the treatments. CD38 is expressed on multiple immune cells, so it makes sense that using daratumumab could lead to an increased need for blood transfusions.
Thanks for pointing that out.
Mark
All myeloma therapies can have significant side effects. Myeloma patients are more apt to be getting blood transfusions than the general population. Do not forget that most of the studies on daratumumab are on relapsed patients, so some of the need for blood transfusions could partially be due to the cumulative toxicity of the treatments. CD38 is expressed on multiple immune cells, so it makes sense that using daratumumab could lead to an increased need for blood transfusions.
Thanks for pointing that out.
Mark
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Mark11
Re: FDA approves Darzalex (daratumumab)
There is a paper from ASH that suggests that pretreatment ex vivo of NK cells with daratumumab fragments is necessary to prevent the daratumumab from killing the NK cells that express CD38. If this is correct, it is important for a patient to receive the full benefit of daratumumab.
https://myelomabeacon.org/resources/mtgs/ash2015/abs/4244/.
https://myelomabeacon.org/resources/mtgs/ash2015/abs/4244/.
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goldmine848 - Name: Andrew
- When were you/they diagnosed?: June 2013
- Age at diagnosis: 60
Re: FDA approves Darzalex (daratumumab)
Good morning, Andrew:
I read this article and it's quite interesting on a couple of levels. In another thread, it was discussed that Elo claimed to be the ONLY immuno-stimulative monoclonal antibody. In your post, the article indicates that at present, Dara will suppress the natural killer (NK) cells, while elo actually stimulates them. That may be the reason, I reckon, that the FDA allowed Elo's claim in the official statement for the drug approval (for elo).
Dara is already quite active, and as we know received fast track approval. Not all of the best combinations and settings have been worked out yet, and this will be an area of active research, with Dara very likely to move up the food chain into newly diagnosand first relapse, to get better responses, FPS, etc., in those settings.
This article, as you point out, indicates that there is the potential to improve further dara's activity by the modification described in the article/abstract, to maintain NK levels. To paraphrase the article, the CD-38 marker is on the multiple myeloma cells, and is dara's target, and the reason it is so active. CD-38 is also expressed on the NK cells, and that is the reason the "good" NK cells also get suppressed.
Pre-clinical trials are the front end of the pipeline for drug development, however, very often, a very promising result in a pre-clinical trial does not pan out for one reason or another. In this case, however, the pre-clinical trial was for an already approved drug. It usually takes several years (3 +, or more) for a promising pre-clinical result to work its way up to an approved treatment. In this case, I hope they figure it out faster than that. Thank you for the interesting post.
I read this article and it's quite interesting on a couple of levels. In another thread, it was discussed that Elo claimed to be the ONLY immuno-stimulative monoclonal antibody. In your post, the article indicates that at present, Dara will suppress the natural killer (NK) cells, while elo actually stimulates them. That may be the reason, I reckon, that the FDA allowed Elo's claim in the official statement for the drug approval (for elo).
Dara is already quite active, and as we know received fast track approval. Not all of the best combinations and settings have been worked out yet, and this will be an area of active research, with Dara very likely to move up the food chain into newly diagnosand first relapse, to get better responses, FPS, etc., in those settings.
This article, as you point out, indicates that there is the potential to improve further dara's activity by the modification described in the article/abstract, to maintain NK levels. To paraphrase the article, the CD-38 marker is on the multiple myeloma cells, and is dara's target, and the reason it is so active. CD-38 is also expressed on the NK cells, and that is the reason the "good" NK cells also get suppressed.
Pre-clinical trials are the front end of the pipeline for drug development, however, very often, a very promising result in a pre-clinical trial does not pan out for one reason or another. In this case, however, the pre-clinical trial was for an already approved drug. It usually takes several years (3 +, or more) for a promising pre-clinical result to work its way up to an approved treatment. In this case, I hope they figure it out faster than that. Thank you for the interesting post.
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JPC - Name: JPC
41 posts
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