Posted by Jeff Berk, BOLT International; I got an email today asking when i was going to shut up about the Arizona weather. I will when the sky stops looking like this:
This notocactus bloomed this morning. The jackrabbits love to chomp on them, spines and all. Does anybody have a good recette de lapin?
In the news: Novartis received approval for use of Gilenya from EMEA as 2nd line therapy for active relapsing remitting multiple sclerosis. Unlike FDA, EMEA did not award a 1st line indication. In the US, Gilenya is priced at $48,000/year. This is higher than Copaxone (glatiramer acetate; Teva; $42,300/yr), Tysabri (natalizumab; Biogen-Idec / Elan; $42,800/yr), Avonex (interferon; Biogen-Idec; $37,544/yr), Betaseron (interferon; Bayer-Schering; $37,294/yr) or Rebif (interferon; Merck-Serono; $36,825/yr).
In this blog I want to talk about how BOLT’s MULTIPLE SCLEROSIS THOUGHT LEADER panel feels about Novartis’ Gilenya. But first, I want to offer a few comments about their pricing strategy. I gave a talk in New Jersey last year (Yeah, I asked myself the very same question). The topic was What’s Going to Jumpstart the Pharmaceutical Industry out of this Recession. My thesis was that there are a few diseases, and MS is one of them, where the systemic cost of the disease is incredibly high because it not only disables the patient in the prime of (usually) her life without shortening her life, but it also removes from full employment a group of friends and relatives who have to serve as caregivers. This slide sums up the $’s we’re talking about:
Couple that with large patient populations who will be on therapy for 30-50 years and you have a really attractive commercial opportunity for pharma.
In a moment I’ll share some of the discussion from BOLT’s Thought Leader panel in December 2010. As you read it, consider the following: while the average cost per year per MS patient in the US is $34,000, this is for all comers. The sweet spot for Gilenya is going to be those 2nd line interferon failures, not treatment naive MS patients. And their annual insurance cost is north of $75,000; before adding in lost wages for family members. So my personal feeling is that Gilenya is properly priced — as a 2nd line agent after interferon or GA.
Here’s the Thought Leader discussion (dated December, 2010):
- Gilenya (fingolimod) is having minimal impact on the market thus far. Some of the tertiary care centers are starting some patients 1st-line, but the majority of our panelists say that at $48,000/yr for drug acquisition + $12,000 for monitoring in the US it is priced well above the pharmacoeconomic break-even point for the payers. Most actual starts are 2nd-line in patients with active lesions, as an alternative to Tysabri. In states where they are allowed to do so (so, not Massachusetts), Novartis is paying some of the patient co-pays, but this does nothing to incentivize the insurance companies. And the cost overwhelms the idea that patients will be able to avoid the injections and flulike symptoms associated with interferon. Patient feedback has been that they are a bit afraid of the mechanism and don’t want to be the first patient to be put on therapy.
“The biggest problem with fingolimod is priced at 48,000 dollars a year. It is way, way too expensive. There is not really any significant impact on the market right now. Occasionally people are writing prescriptions for it, but because it is so expensive it is doubtful that maybe one in ten of those people are going to get started on it. So there is a lot of trepidation about fingolimod. And then with this price it is a very expensive drug at 48,000 dollars a year”.
“What the company is doing you probably know that is that they are subsidizing patients, not in Massachusetts because they cannot do that in Massachusetts. But in other states they can actually pay the patient back their copay”.
“I want to build on that comparison for a moment. I look at Gilenya and the number I am throwing around is $48,000 a year. Yeah, plus the vigilance testing because that 48,000 is drug cost but I am thinking low 60s if you want to consider the doctor’s visits and the OCTs, PFTs and various other testing”.
“Nobody wants to be injecting these interferons or GA all the time. No they don’t. They are sick and tired of shots. They are sick and tired of flu-like symptoms. You have an occasional patient who says I am okay on this stuff, but most patients say boy you have got an oral medication, I want it; except when they hear $48,000 a year then they are not interested”.
“What therapies have those patients for whom you are writing fingolimod what was their prior therapy, if any? Mostly they are patients who have been on interferons or Copaxone and who are experiencing either relapses or active lesions. So these are patients who we would offer Tysabri to. So one of my patients I saw last week he is exactly at this juncture. He was on interferon and was having active lesions. We discussed all the options between Tysabri, between fingolimod, between going on clinical trials, and he elected to go on the Tysabri. He chose Tysabri? Yes”.
“I am impressed that patients are not asking for the fingolimod. I expected that there is going to be a huge interest from patients and I think patients are a little bit more reluctant to jump on a new medication these days. After the issues with the Tysabri, they are a little bit more cautious. I think they are interested; they are just a little bit scared. They want to get more data like other patients taking it before they jump in”.
(A panelist who is seeing a fair # of 1st-line starts on Gilenya): “It may be Los Angeles and that may explain why people are more likely to be risk tolerant, or they may be my patients which self selects for a certain amount of risk tolerance, or because I am a specialty center and they are already oriented to take risk, but I have no difficulty in getting people to look at the data with me and say this is reasonable. But are those treatment-naïve patients? Yeah. Virgin. And people, as you know, the breakout is there is virgin and I think in our practice we cover about 2300 patients or so. So we have had I think 27 or 28 virgin starts, Gilenya, and we have had another 50 or so people who are either suboptimal or just sick and tired and now they are on their second decade of injectable therapy. They were noncompliant and were just giving us the bottom line saying we are not going to take this anymore and we have to switch. Or we were thinking about giving them something else other than their monotherapy or monotherapy with pulse steroid, which is our usual. So I am waiting to see what kind of difficulties we have because we have an electronic medical record at USC that allows me to put in requests or my staff to put in requests for the testing or oversight, and I can get that documentation back. This is all done pretty adeptly here, so it is not as difficult to integrate care as it might be elsewhere”.
“Is Novartis allowed to help your patient with the copays? Oh yeah. They have got a system just like Acorda had a system. Actually it is not like Acorda because Acorda is doing everything through specialist pharmacy and you can get Gilenya at your local. But they are monitoring and when you request after you the EOB, the explanation of benefits, then Novartis kicks in. I am not remembering what their limit is, but they will contribute some amount. I don’t remember right now. And they also integrate care. They have got nurse managers that are helping, if you wanted, identify doctors who will do some of the vigilance testing but we haven’t needed that. And that is for the community neurologist? It is for people who need it I guess. It is for anybody who can’t find people to do this stuff and document it the way you need. And to help ease the stress on the staff of the doctor’s office that have to make sure the stuff is in line when the drug is being given”.
“Have you started any of these patients first line? I don’t think I have started any first line yet. I don’t think. I am not entirely sure. I think I have one in the pipeline. And what makes that patient a good candidate? They wouldn’t take injectables. In New York, can Novartis help the patients with these copays? To the best I know they can. The only one where I think it is an issue is Medicare. In Massachusetts they can’t. Oh okay. That is a little bizarre isn’t it? That is their law. I understand but it is sort puts some burden on the patient”.
- With time, and assuming that there are no toxicity surprises, fingolimod will move into a 1st-line paradigm. The three major toxicities associated with fingolimod are a 75% decrease in lymphocyte count, a slight increase in the risk of infection (Herpes zoster) and a still-unresolved question of increased risk of malignancy. Contrary to the positioning message from Novartis, many neurologists still view fingolimod as an immunosuppressive agent rather than an immunomodulating drug, and since it crosses the placenta there is an unresolved question as to whether the drug can interfere with pregnancy. 75% of CIS patients are fertile young women.
“Fingolimod is a good first line drug”.
“As time moves on and no new safety concerns arise Gilenya will attract more first line use and there are people who don’t want injections and therefore it will be first line right now for those people”.
The pharmacoeconomic argument is that they reduce relapses enough so that it justifies the cost of the drug because their insurance companies will pay that much money in healthcare. It is a bogus argument and it doesn’t work because even though it had a 52% reduction in relapse rate it is a far cry – the populations of patients in the study were so different that you really can’t compare it to the older clinical trial data. It is just apples and oranges. So basically it is as good as what we have now but it is no better.
“It drops lymphocyte counts by 75% so they are basically a quarter of their baseline values. There is a slight increased risk of infection and there could be a risk of malignancy. The jury is still out on that one”.
“I think fingolimod’s problem is that it is an agent that needs to be monitored. It is viewed by many of the neurologists as an immunosuppressive agent, despite the positioning of Novartis as an immunomodulator. From that point of view it also has the whole issue regarding pregnancy and the crossing of the placenta. If you think about the CIS patient, very early patients, 75 percent of these patients are fertile young woman. If you propose to anybody that the medication they are going to take may potentially interfere with their fertility a lot of patients become very concerned with it”.
- Being an oral formulation is a big advantage. Patients really hate the frequent injections with interferon and Copaxone (glatiramer acetate). But having to wait in the physician’s office for 6 hours upon initiation of therapy is very inconvenient for the patient, and it requires a nurse to check vital signs about once per hour. FDA has mandated this due to bradycardia. And patients are being fairly subdued in their enthusiasm for a new mechanism of action because of the Tysabri experience.
“Its big advantage is that it is oral and that is a significant advantage”.
“It is a little bit of a task to get all the information together, but not horrible and then we watch them for the six hours here, if that is convenient for the patient, I can get them started. Does anybody really worry about bradycardia at the low dose or is that simply and FDA requirement that you keep those patients there for that six hours? It is the requirement. And it is a new drug and it is okay until we get more experience with it to see what the true incidence is”.
“First dose monitoring isn’t a big deal”.
“We have started patients on it so we do have patients who have started. It was a little bit of a thing to organize when we are going to get them in and do the six hour observation but basically there are some patients who are willing to try it. But it is not the, “Oh my God, I’ve got to get it” that we have seen with the Tysabri when it first came out”.
“Safety wise I don’t think fingolimod is not as bad as other drugs. So I am not really concerned about the safety profile. I think the proof is going to be by observing for a few years outside of the clinical trial to see what kind of things we will start to see. But from what we know at this point the safety profile is not that concerning. It is a little bit tricky because the six hour observation makes it just awkward. You just have to bring the patients in and sit them in the clinic for six hours. You are supposed to monitor for bradycardia. So we get their pulses and we just watch them. But at the lower dose my understanding is that the bradycardia is not that much of an issue? But that is the recommendation from the FDA that you have to observe them for six hours. Yes. It is not by choice that we are doing it”.
“I am not having any difficulty starting the drug. I just stick them out in my waiting room and take their vital signs every hour. So what have your experiences been? Any complaints? No”.