RheumNow Week In Review - 28 July 2017 Save
RheumNow Week In Review - 28 July 2017 by Dr. Cush
Transcription
Hey now. I'm Jack Cush, executive editor of roomnow.com. This is the RheumNow we can review. It is the 07/28/2017. In this week in the news, we have a lot of interesting news.
A lot of it comes from the regulatory side of our business with, new drug approvals, new drug failures, new drug removals, and some drugs hitting the skids. But first, an analysis of hospital cost of biologic infusions was undertaken at a single center it looked like, and showed that, the cost of biologics, was quite high as you would imagine, especially in the care of rheumatoid arthritis patients. Compared to other drugs, biologics took up the greatest percentage of the cost of care, amongst all the therapeutic options. Specifically, the average price per infusion for our drugs was 36,000 for rituximab, 36,000 for tocilizumab, fliximab was higher at almost 45,000 and abatacep was actually the highest at 46,000. Now, of course, some of these are weight based dosing and, there's some variability.
When you exclude the drug costs, it looks like that the cost of infusion was also made up of, the cost of personnel and the administration, which is about 50% of the total cost. So, an interesting, set of numbers for those of you who track numbers. An interesting advance for BMS has been the approval of Avatacep or Arencia in the, EU for use in psoriatic arthritis. As you know, a few weeks ago, the FDA also approved Arencia for, patients with active psoriatic arthritis in The United States. It's good to see that there's some consistency in the regulatory process across the pond.
The NIH has launched a trial looking at a virus, I'm sorry, virus, a vaccination against the chikungunya virus. It's called a MV chick v vaccine. It's a recombinant live virus vaccine. It's a phase one and phase two trial, two sort of phases that's, being undertaken in patients who may be at risk and in regions where they may be at risk. We'll await those results.
An interesting analysis of over a thousand patients with ANCA positive vasculitis looked at the incidence of ocular disease, specifically inflammatory ocular disease. Half the patients had eye pain, sixteen percent lost their vision, and amongst the many things that we see, some common diagnoses including scleritis in twenty two percent, episcoritis in twenty one percent, and uveitis in nine percent. The analysis also went on to look at how they were treated. Not surprisingly, many of them received systemic corticosteroids, some local steroids and other measures. So, nice review of ocular involvement in patients with ANCA positive vasculitis.
A study from Stocios Smolin's group tells us what we might have suspected that, both guselkumab and IL-twenty three inhibitor and, Stellara, ustekinumab, an IL-twelve twenty three inhibitor does not work in patients with rheumatoid arthritis. This was compared to a placebo population. The results were, you know, forty percent, fifty percent for almost every group, but not different from placebo, not significantly different than placebo. There were some advantages for those therapies, but again, it did not, meet the benchmark set by placebo or did not surpass that benchmark. So, you won't be seeing those products being developed for rheumatoid arthritis.
An interesting analysis compared, the ability of ultrasound and deck scanning, that's dual energy CT scans, in quantifying TOFI within the joint of patients who have gout. Now, you might have thought of that the great pictures and specificity of the deck scans would sort of win hands down, but in fact, the deck scans, the ECTs, had a lower sensitivity compared to ultrasound, at least looking within the joints. So that was somewhat surprising, and probably only of interest to the GalpMaven. Congratulations. Some big regulatory news.
We announced earlier in the week that, Samsung Bioepis, the company that has made the new Remicade biosimilar called Renflexis, is now launching the drug and it's being marketed in The United States by Merck. A few days later, they came out with news that they were gonna undercut the price of biosimilars that's currently on the market. As you know, Inflectra, marketed by Pfizer, hit the market, earlier this year with a 15 discount compared to Remicade. Now, that didn't really, get a lot of approval from rheumatologists who are well aware that the European equivalent on discounts is at least 50% on average across Europe and as high as 70%. Why we're getting the shaft in The United States with a 15% discount?
Not sure why I'd want to jump to a new, somewhat hard to understand use of biosimilars. Well, Merck and Samsung have actually gone one step step further and now it's a 35% discount. So the biosimilar pricing wars have begun. It'll be interesting to see how this is gonna pan out. The actual numbers on pricing is in the the report.
It's like over 1,000 for a vial for Remicade and 900 it was 1,100, 900 something for the, Inflectro at a 15 percent discount, but 700, in change for the newer Renflexis also a Remicade and infliximab biosimilar. So it'll be interesting to see how this plays out, especially as we have two more approved biosimilars that are TNF inhibitors. Amjevita is the adalimumab biosimilar from Amgen and Aralzi is the etanercept biosimilar from Sandoz. Those have yet to hit the market and be priced. It'll be interesting to see what happens when they are in the competitive arena.
Baricitinib was a very important new advance in JAK inhibitor development, great trials, over 3,000 patients. A few months ago, they received the unfortunate news that they had a complete response letter, which was the FDA asking for more information and they could not approve the application as it was. Well, they received further bad news this week that the FDA has denied their application as it is and now they have to go back to the drawing board. The FDA is asking for new trials. They have a safety concern specifically around the issue of thromboembolic events.
What they found was that in over three thousand patients treated, they had five cases of thromboembolic events including pulmonary emboli in patients on, baricitinib, the higher dose, the four milligram dose, none on the two milligram dose and zero on the matched placebo population. This obviously, has is without explanation, and will require further study and analysis of all their data set, and possibly a new trial. If they're going to do a new trial, it's not going to launch for a few years. Some estimates say this drug will not be approved until as late as 2021 after they meet with the FDA and come to some conclusions about what needs to be done next. At issue here is whether or not this imbalance of a safety signal, zero for placebo, and five events, thrombotic events on the drug, is that a real issue?
Is that a major issue? Heretofore, it really wasn't, on the radar for those of us who looked at the data year by year at ACR and ULAAR, you weren't seeing these events until you don't see it until you get a very large data set together and then all of a sudden there seems to be something there. You have to know the background rate of VTE and thromboembolic events in RA and it is increased. RA patients, have a significant, as much as a twofold or more increased rate of venous thromboembolic events, compared to, matched populations. That number is not higher when you take TNF inhibitors.
That number, you know, could be obviously modified by other factors well known to cause thromboembolic events. So in these three thousand patients at that rate, would that number have been expected? Is this sort of random chance that we had none in, the zero population, the placebo population, but had five as you might expect in over three thousand patients with RA? To me, this reminds me of what happened with the TNF inhibitors and non Hodgkin's lymphoma. In the first six thousand three hundred and three patients treated with TNF inhibitors, that includes Enbrel, Remicade, and Humira, there were six cases of non Hodgkin's lymphoma in those that received a TNF inhibitor, but none in those that were on placebo during the placebo controlled portion of those trials.
Now, the FDA then had a hearing, looked at all the data including those that went into open label extension, identified the total of twenty three patients and identified an SIR rate of two to six for one, two to six fold increase risk for non Hodgkin's lymphoma in these trials. Turns out that that was a population risk. When you looked at all the large populations, hundreds of thousands of patients, 40,000 patients from big centers, they showed the same SIR rate, the same relative risk of developing lymphoma in patients with rheumatoid arthritis. Hence, there is no increased risk of non Hodgkin's lymphoma and lymphoma in RA patients on TNF inhibitors because it's the same rate as if they're not on a TNF inhibitor. Well, the question remains, will this be seen when there's an analysis done of this thromboembolic events in patients on varicitinib?
Another surprise came this week with Benlysta. I didn't know this was happening. Benlysta actually has done a trial, the BLISS SC trial. Over 800 patients tested the, efficacy and utility of receiving belimumab as a subcutaneous injection using two hundred milligrams per injector. That's both a prefilled syringe and an auto injector.
It's now FDA approved and will be on the market soon and will become a pharmacy benefit where a hetero-four, the infusible belimumab was a medical benefit. So, it'll be interesting to see how this plays out. You may know that that when other drugs who had first infusible forms then added an injectable form such as Actemra and Arencia, that the subcutaneous market for those products rose to about one third or 40% of their total market. So, it's going to be an interesting, to see how this, changes the uptake and use of, belumumab in patients with active lupus. And lastly, there is a report, a population based report on the risk of developing, pulmonary embolism in patients with lupus, where it's been shown that there's a twofold increased risk.
Well, that's it for this week at RheumNow. Tune in next week for more good news and updates from the world of rheumatology. We're looking to get your cases and interesting quotes and whatnot, so email us at info roomnow dot com if you got an interesting case for curbside consults or, a favorite rheumatology quote or a gem that you use when teaching rheumatology. Thanks very much. We'll see you next week.
A lot of it comes from the regulatory side of our business with, new drug approvals, new drug failures, new drug removals, and some drugs hitting the skids. But first, an analysis of hospital cost of biologic infusions was undertaken at a single center it looked like, and showed that, the cost of biologics, was quite high as you would imagine, especially in the care of rheumatoid arthritis patients. Compared to other drugs, biologics took up the greatest percentage of the cost of care, amongst all the therapeutic options. Specifically, the average price per infusion for our drugs was 36,000 for rituximab, 36,000 for tocilizumab, fliximab was higher at almost 45,000 and abatacep was actually the highest at 46,000. Now, of course, some of these are weight based dosing and, there's some variability.
When you exclude the drug costs, it looks like that the cost of infusion was also made up of, the cost of personnel and the administration, which is about 50% of the total cost. So, an interesting, set of numbers for those of you who track numbers. An interesting advance for BMS has been the approval of Avatacep or Arencia in the, EU for use in psoriatic arthritis. As you know, a few weeks ago, the FDA also approved Arencia for, patients with active psoriatic arthritis in The United States. It's good to see that there's some consistency in the regulatory process across the pond.
The NIH has launched a trial looking at a virus, I'm sorry, virus, a vaccination against the chikungunya virus. It's called a MV chick v vaccine. It's a recombinant live virus vaccine. It's a phase one and phase two trial, two sort of phases that's, being undertaken in patients who may be at risk and in regions where they may be at risk. We'll await those results.
An interesting analysis of over a thousand patients with ANCA positive vasculitis looked at the incidence of ocular disease, specifically inflammatory ocular disease. Half the patients had eye pain, sixteen percent lost their vision, and amongst the many things that we see, some common diagnoses including scleritis in twenty two percent, episcoritis in twenty one percent, and uveitis in nine percent. The analysis also went on to look at how they were treated. Not surprisingly, many of them received systemic corticosteroids, some local steroids and other measures. So, nice review of ocular involvement in patients with ANCA positive vasculitis.
A study from Stocios Smolin's group tells us what we might have suspected that, both guselkumab and IL-twenty three inhibitor and, Stellara, ustekinumab, an IL-twelve twenty three inhibitor does not work in patients with rheumatoid arthritis. This was compared to a placebo population. The results were, you know, forty percent, fifty percent for almost every group, but not different from placebo, not significantly different than placebo. There were some advantages for those therapies, but again, it did not, meet the benchmark set by placebo or did not surpass that benchmark. So, you won't be seeing those products being developed for rheumatoid arthritis.
An interesting analysis compared, the ability of ultrasound and deck scanning, that's dual energy CT scans, in quantifying TOFI within the joint of patients who have gout. Now, you might have thought of that the great pictures and specificity of the deck scans would sort of win hands down, but in fact, the deck scans, the ECTs, had a lower sensitivity compared to ultrasound, at least looking within the joints. So that was somewhat surprising, and probably only of interest to the GalpMaven. Congratulations. Some big regulatory news.
We announced earlier in the week that, Samsung Bioepis, the company that has made the new Remicade biosimilar called Renflexis, is now launching the drug and it's being marketed in The United States by Merck. A few days later, they came out with news that they were gonna undercut the price of biosimilars that's currently on the market. As you know, Inflectra, marketed by Pfizer, hit the market, earlier this year with a 15 discount compared to Remicade. Now, that didn't really, get a lot of approval from rheumatologists who are well aware that the European equivalent on discounts is at least 50% on average across Europe and as high as 70%. Why we're getting the shaft in The United States with a 15% discount?
Not sure why I'd want to jump to a new, somewhat hard to understand use of biosimilars. Well, Merck and Samsung have actually gone one step step further and now it's a 35% discount. So the biosimilar pricing wars have begun. It'll be interesting to see how this is gonna pan out. The actual numbers on pricing is in the the report.
It's like over 1,000 for a vial for Remicade and 900 it was 1,100, 900 something for the, Inflectro at a 15 percent discount, but 700, in change for the newer Renflexis also a Remicade and infliximab biosimilar. So it'll be interesting to see how this plays out, especially as we have two more approved biosimilars that are TNF inhibitors. Amjevita is the adalimumab biosimilar from Amgen and Aralzi is the etanercept biosimilar from Sandoz. Those have yet to hit the market and be priced. It'll be interesting to see what happens when they are in the competitive arena.
Baricitinib was a very important new advance in JAK inhibitor development, great trials, over 3,000 patients. A few months ago, they received the unfortunate news that they had a complete response letter, which was the FDA asking for more information and they could not approve the application as it was. Well, they received further bad news this week that the FDA has denied their application as it is and now they have to go back to the drawing board. The FDA is asking for new trials. They have a safety concern specifically around the issue of thromboembolic events.
What they found was that in over three thousand patients treated, they had five cases of thromboembolic events including pulmonary emboli in patients on, baricitinib, the higher dose, the four milligram dose, none on the two milligram dose and zero on the matched placebo population. This obviously, has is without explanation, and will require further study and analysis of all their data set, and possibly a new trial. If they're going to do a new trial, it's not going to launch for a few years. Some estimates say this drug will not be approved until as late as 2021 after they meet with the FDA and come to some conclusions about what needs to be done next. At issue here is whether or not this imbalance of a safety signal, zero for placebo, and five events, thrombotic events on the drug, is that a real issue?
Is that a major issue? Heretofore, it really wasn't, on the radar for those of us who looked at the data year by year at ACR and ULAAR, you weren't seeing these events until you don't see it until you get a very large data set together and then all of a sudden there seems to be something there. You have to know the background rate of VTE and thromboembolic events in RA and it is increased. RA patients, have a significant, as much as a twofold or more increased rate of venous thromboembolic events, compared to, matched populations. That number is not higher when you take TNF inhibitors.
That number, you know, could be obviously modified by other factors well known to cause thromboembolic events. So in these three thousand patients at that rate, would that number have been expected? Is this sort of random chance that we had none in, the zero population, the placebo population, but had five as you might expect in over three thousand patients with RA? To me, this reminds me of what happened with the TNF inhibitors and non Hodgkin's lymphoma. In the first six thousand three hundred and three patients treated with TNF inhibitors, that includes Enbrel, Remicade, and Humira, there were six cases of non Hodgkin's lymphoma in those that received a TNF inhibitor, but none in those that were on placebo during the placebo controlled portion of those trials.
Now, the FDA then had a hearing, looked at all the data including those that went into open label extension, identified the total of twenty three patients and identified an SIR rate of two to six for one, two to six fold increase risk for non Hodgkin's lymphoma in these trials. Turns out that that was a population risk. When you looked at all the large populations, hundreds of thousands of patients, 40,000 patients from big centers, they showed the same SIR rate, the same relative risk of developing lymphoma in patients with rheumatoid arthritis. Hence, there is no increased risk of non Hodgkin's lymphoma and lymphoma in RA patients on TNF inhibitors because it's the same rate as if they're not on a TNF inhibitor. Well, the question remains, will this be seen when there's an analysis done of this thromboembolic events in patients on varicitinib?
Another surprise came this week with Benlysta. I didn't know this was happening. Benlysta actually has done a trial, the BLISS SC trial. Over 800 patients tested the, efficacy and utility of receiving belimumab as a subcutaneous injection using two hundred milligrams per injector. That's both a prefilled syringe and an auto injector.
It's now FDA approved and will be on the market soon and will become a pharmacy benefit where a hetero-four, the infusible belimumab was a medical benefit. So, it'll be interesting to see how this plays out. You may know that that when other drugs who had first infusible forms then added an injectable form such as Actemra and Arencia, that the subcutaneous market for those products rose to about one third or 40% of their total market. So, it's going to be an interesting, to see how this, changes the uptake and use of, belumumab in patients with active lupus. And lastly, there is a report, a population based report on the risk of developing, pulmonary embolism in patients with lupus, where it's been shown that there's a twofold increased risk.
Well, that's it for this week at RheumNow. Tune in next week for more good news and updates from the world of rheumatology. We're looking to get your cases and interesting quotes and whatnot, so email us at info roomnow dot com if you got an interesting case for curbside consults or, a favorite rheumatology quote or a gem that you use when teaching rheumatology. Thanks very much. We'll see you next week.
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