After the presentations, there will be a question and answer session.
This meeting is being recorded.
You are invited to send in questions for this throughout the entire session using the Q&A functionality of Zoom. In addition to that, you may also raise your virtual hand to address your questions verbally. For participants joining via phone, to raise your hand, use star 9 on your phone's dial pad. When you then get selected to ask your questions, please follow the instructions from the phone and press star 6 to unmute yourself. At this time, it's my pleasure to introduce you to Karl Mahler, Head of Investor Relations and Group Planning. Karl, the stage is yours.
Yeah. Thanks a lot, Henrik. Welcome everybody to our fifth science call this year. We have one hour reserved for you, half an hour for presentation and half an hour for the Q&A. Of course, if you find difficulties or have difficulties to enter into the Zoom system, which I don't assume now, you can also, of course, drop me an email directly to karl.mahler@roche.com. I'm joined today by Kathryn Wagner. She is the Vice President of Neuromuscular Disorders Clinical Development with Roche. Many of you may know her from her previous jobs and engagements. She was the director of the Center for Genetic Muscle Disorders of the Kennedy Krieger Institute. She was professor at Johns Hopkins University, and she's well-known for her initiatives in the whole CNS field, but in particular on the Duchenne disease research.
I'm sure you will also may have some questions later on. We have during the Q&A session also Paulo Fontoura with us. He is the head of the development for CNS. Simona Skerjanec, head of the GPS CNS sections of basically the marketing part. Paulo is doing the development part. We have also Kavita Patel with us. She is the lifecycle lead for Evrysdi. Actually, if you look at the key late-stage news flow, we had a really good year so far. We're on a very good way to file faricimab by first half. That is all on good way for BMD and DME. Two good readouts for the dual antibody to fight COV2, the outpatient data, and the post-exposure prophylaxis. Tecentriq was one of the focus of the past ASCO, adjuvant non-small cell lung cancer. Actually, we received a very good feedback from ASCO.
Today we are focusing on Evrysdi type one, two, and three in SMA. A few data which we will focus later on. Just to do a bit of an advertisement for the rest of the year. We still have the Pharma Day upcoming, the 14th of September, an ESG event. We haven't done one for long, I have to say. It'll be the first one actually. This year we do a lot in ESG. We haven't done a lot of public announcements on it. We are really doing a lot, placing ourselves in the Dow Jones Sustainability Index every year now as the number one position. We felt that it's a good time to share some of those efforts with you. We have ASH upcoming and also our digital event, which we do basically every year.
If you look at the broad pipeline which we have in CNS, you can see that I dare to say we have the broadest and deepest pipeline and also a portfolio in the industry. Ocrevus is launched. Ponesimod is in phase III. We have Enspryng launched. This is in neuroimmunology. Neurodegeneration, Alzheimer, I am sure you will have some questions on that part later on. In phase III, reading out next year, Parkinson phase II, III. Neuromuscular disorders, Evrysdi, focal point today, and one of the prior research also from Kathryn, BMD, Duchenne muscular dystrophy and disease. Here we have also received some positive data, I have to say, from our partner recently and a bit an earlier stage, bipolar neurodevelopment, psychiatry, Angelman syndrome, which has moved into phase I, and schizophrenia. There is a lot to do.
If the focal point for today is basically on Evrysdi, meaningful evidence being generated across the broad program, spanning types from one, two, and three SMA, naive and pre-treated patients, newborns to 60 years old. We have included also real-world spectrum SMA data, which is good because here we have really an intensive research done over the past. The focus today is on RAINBOWFISH. This is basically infants from birth to six weeks old. Smaller patient numbers, I have to say, in the trial, really nice data. Very encouraging for patients. The JEWELFISH, first trial in patients from 1 to 60 years old, a wide range of disease severity being presented at this year's conference. With this one, I wanted to hand over to Kathryn. Kathryn, over to you, please.
Hello. It's a pleasure to talk to you today about interim data of Roche's JEWELFISH and RAINBOWFISH in Risdi for SMA. These findings add to a growing body of evidence for Evrysdi in a wide range of ages and types of SMA and help lead us in our understanding of how we can continue to meet the ongoing unmet medical needs of the diverse SMA population. Next slide. JEWELFISH is the first study of its time. Next slide. This study is in a broad age range from 1 year old to 60 of types 1 through 3, and a diverse heterogeneous population in terms of disease severity, with many more severely affected patients that are usually enrolled in a clinical trial of SMA. These patients were all previously treated with a disease-modifying therapy for SMA.
Our primary analysis will be at 24 months, but we are presenting now some 12 months data on the safety, PD, and exploratory efficacy data for the JEWELFISH population. Next slide. Here you can see the study design, the primary objective of this trial, as I mentioned, is safety, but we will also obtain data on PK/PD relationships and some exploratory functional endpoints such as the MFM32. Next slide. This slide shows the baseline characteristics of the JEWELFISH population, and I will just call your attention to the final column where you can see again the ages range from 1 to 60. The types included types one, two, and three, SMN copy numbers from one to four. The motor function was diverse and more severe, as I mentioned, than many SMA trials.
For example, 63% of patients had a baseline Hammersmith Functional Motor Scale Expanded score of less than 10, and that is frequently an exclusion criteria for clinical trials. Again, high degrees of scoliosis, 83%, and severe scoliosis in almost 40%. This represents the real world. This represents what physicians will be seeing in their clinics. Next slide. Why would a patient or a caregiver enroll in JEWELFISH to receive risdiplam? The reasons varied somewhat depending on what the previous treatment was. For those who had previously received risdiplam-- sorry, nusinersen, they chose to switch primarily due to treatment-related tolerability concerns such as intrathecal administration, which was followed by lack of efficacy or a loss of efficacy, and those two comments on efficacy total of 30% of the population. Other reasons were caregiver preference and patient preference.
In terms of those who had previously been treated with ZOLGENSMA, the primary reason to enroll in JEWELFISH and receive risdiplam was the hopes of an additional benefit in 57%, caregiver preference, and a lack of efficacy of the gene therapy were other reasons. Next slide. There are very low rates of discontinuation. In the JEWELFISH study, only 9 out of 174 enrolled patients discontinued. This is 5%. There were 76 patients who enrolled who had previously received nusinersen. 4 withdrew, and you can see their reasons for withdrawal below. 14 patients had previously received ZOLGENSMA, and there have been no withdrawals from that cohort. Next slide. There were no treatment-related safety findings that led to withdrawal in any JEWELFISH patients. On this slide, you can see the total number of AEs and SAEs. There was only 1 treatment-related SAE.
This was a child who had supraventricular tachycardia that the investigator felt might be related to the drug. However, it resolved despite risdiplam dosing continuing. Next slide. The SAEs and the AEs in the JEWELFISH population were very similar to what we have seen in previous SUNFISH trials and are just reflective of the underlying disease. Remember, these patients have had SMA and the manifestations of SMA for many years, some up to 60 years. They have the morbidities associated with that, including among the most high upper and lower respiratory illnesses. It is worth pointing out that in the patients who were treated with ZOLGENSMA and then subsequently treated with risdiplam, their AE profile was very similar to that of the other cohorts who have received different treatments, and again, very similar to naive SMA patients who received risdiplam. Next slide.
Risdiplam led to a rapid and sustained increase in the SMN protein levels in blood. Here you can see that SMN protein levels approximately doubled in the first month of treatment and then remained stable for the year. Next slide. As I mentioned, the primary objective of this study was to look at safety in previously treated SMA patients who now receive Risdiplam, but we did also look at some exploratory efficacy measures, and an interim data analysis demonstrated an overall stabilization in motor function at month 12 in patients who began to receive Risdiplam following previous treatments. This shows the change in the MFM32, which is a measure of both fine and gross muscle function, and there is essentially no change over 1 year.
We can't underestimate the importance of stabilization in this population, many of whom are older, many of whom, as I've mentioned, are severely affected. In fact, SMA Europe recently published a paper in neuromuscular disorders where of 1,500 responses, 97% of them said stabilization is indeed progress. Next slide. In conclusion, the JEWELFISH population is broad and heterogeneous with a high degree of motor impairment at baseline, reflecting the real world SMA population. The AEs and SAEs were reflective of underlying disease. Risdiplam treatment has shown a sustained greater than twofold increase in median SMN protein levels versus baseline. There were low rates of discontinuation, and interim exploratory efficacy data showed that overall stabilization in motor function was observed in patients who began treatment with risdiplam following previous treatments.
Again, the JEWELFISH study is ongoing, and primary analysis will be conducted at month 24. Next slide. Let's switch gears to talk about RAINBOWFISH. This is a study of risdiplam in individuals with presymptomatic spinal muscular atrophy. As I'm sure you are well aware that Risdi has been approved in 44 countries for individuals 2 months and older. However, ideally, we would really like to be able to treat babies before they had substantial motor neuron loss and before they manifest weakness. This is becoming more and more possible as newborn screening is adopted. RAINBOWFISH is looking to see what is the appropriate dose and the efficacy and safety of treating presymptomatic individuals. We can go on to the next slide. This is a multicenter, open label, single arm study of risdiplam in infants with genetically diagnosed and presymptomatic SMA.
They could enroll up to six weeks or 42 days at the time of their first dose. The primary endpoint will be when the population that is being studied for the primary endpoint, which is able to hold one's head for greater than five seconds at month 12, has been reached. There are a number of secondary endpoints which include functional and PK/PD and safety. We're going to report here the first time of just the first five patients to reach this 12-month endpoint. Next slide. The baseline characteristics of the 12 infants currently enrolled show that they had an age of 16 to 40. Five of them had two SMN2 copy numbers, and seven had greater than two copy numbers.
Of the five infants that have been treated for greater than 12 months. Two of these infants had two SMN copy numbers, and three infants had greater than two SMN copy numbers. Next slide. We are just really pleased to see that infants treated with risdiplam for at least 12 months achieve motor milestones on par with their healthy peers. 100% have head control, 100% of sitting, rolling, crawling. four out of five can stand unaided. four out of five walk independently. One is standing with support and bouncing, and we have every reason to hope that he will also achieve these motor milestones. 80% of the infants scored a maximum on a HINE-2 with a total score of 26, and this included 1 infant with two SMN copies, and one infant with two SMN copies had a HINE-2 score of 23.
Just to put this in perspective, an individual with two SMN copy numbers would most likely manifest as a type 1 SMA baby who would have a HINE-2 score of zero. Okay, next slide. Another way of looking at this data is by looking at motor milestones over time, and the gray bars are the WHO windows of achievement in healthy individuals. The symbols are the achievement of motor milestones as observed at the study visit. They're not necessarily when the motor milestone was first demonstrated, but it's when they were first demonstrated in the clinic. Some of the clinic visits were delayed because of COVID. Notwithstanding that, you can see that the majority of individuals reached some very complex motor function milestones, such as crawling on their hands and knees, standing, walking independently within the range of normal healthy infants. Next slide.
The infants treated with risdiplam for at least 12 months reached a near maximum CHOP INTEND score by four to five months of age. Four out of five infants scored the maximum score of 64, and one infant scored a score of 63. Again, to put this in context, babies with two, three, four SMN copy numbers rarely go above 40 on a CHOP INTEND score at any time and then dramatically decline in function. This is really showing us that risdiplam has rescued the SMA phenotype from these individuals. Next slide. There were no treatment related SAEs reported in pre-symptomatic individuals treated with risdiplam. Again, here you can see the total number of AEs and SAEs. Next slide. Interestingly, the AEs now were reflective of symptoms and signs that normal individuals under the age of one have. Not reflective of underlying SMA.
Nasal congestion, cough, teething, vomiting, et cetera. Next slide. In summary, RAINBOWFISH, most of the infants treated for greater than 12 months achieved motor milestones within the WHO windows for healthy children. As of the data cut, all 5 who had received risdiplam for 12 months reached a maximum score of 64 on the CHOP INTEND. There were no treatment related SAEs reported in pre-symptomatic infants treated with risdiplam now for up to 18.1 months. I think the risdiplam story is really the future of SMA, where we treat individuals prior to their manifesting disease and allow them to grow up as normal children. Last slide, I think.
Just to summarize, JEWELFISH was the first trial in a diverse SMA population, ages from 1 to 60, who received prior treatment, which showed a consistent safety profile and a greater than 2-fold increase in SMN protein levels and stabilization in motor function. In RAINBOWFISH, pre-symptomatic babies with SMA treated with risdi for at least one year were able to sit, stand, and walk in preliminary data, achieving motor milestones within the WHO windows for healthy children. We are looking forward to completing these trials JEWELFISH and RAINBOWFISH with speed and with quality, and fulfilling our commitment to the SMA community to provide this drug to a diverse population globally. Thank you.
Many thanks. Very good. We have now all of us here on stage in brackets. I have already seen a lot of interest in Q&A. Let's start with Emmanuel Papadakis. Emmanuel, I open the line.
Thank you for taking the question. Emmanuel Papadakis from Deutsche Bank. Perhaps just a question on JEWELFISH. You hopefully presented that one chart with functional benefit by MFM32. You didn't provide the split by patients that previously received ZOLGENSMA versus SPINRAZA. Could you just give us any kind of qualitative direction? Did it differ? Was it very similar regardless of what therapy patients had previously received? Just your thoughts on the implications of that for justifying, I don't know if you'd call it combination use, but subsequent use of Evrysdi for patients that have previously received ZOLGENSMA, either lack of apparent improvement in functional status. Does that influence your thinking about whether that would be justified? Second question, we saw some very interesting data at conference from apitegromab combination with SPINRAZA.
I would love to hear your thoughts on the potential implications of that, and indeed, whether you will now consider collaborating, supporting a trial combination of risdiplam with apitegromab. Thank you.
I think your question had three parts. The first question was whether we have seen differences in improvement or stabilization in function depending on which pre-treatment or previous treatment the individuals have had. As you saw, we have some fairly small subgroups, such as those who had Zolgensma were 14 patients, and we really haven't done that type of subgroup analysis on the preliminary efficacy measure. Your second question, I believe, was to comment on the combined use of Zolgensma and risdiplam. I would first say that the wide range of Evrysdi studies across ages, types, and disease severities has shown efficacy as a monotherapy of risdiplam. That said, there are currently families and physicians who are choosing to put children who have received gene therapy also on risdiplam. That is part of the real world that is out there.
We do hope that JEWELFISH will continue to provide us data on the efficacy and safety of doing so. We believe at this point that is safe, and as I mentioned, we have just preliminary data on efficacy. I think the third question of SPINRAZA and risdiplam, I am going to see whether my colleague, Kavita, would like to answer.
With SPINRAZA and risdiplam, we've seen that currently in the market that 2/3 of patients that have been previously treated are being switched from SPINRAZA for risdiplam today. That does exist, as Kathryn Wagner said, that we do see previously treated patients being moved to risdiplam.
The potential agent which is here to do any kind of trial. I have to admit, I have to skip this one. Maybe, Paulo, you have any idea or I'm not sure if there's anything planned here in terms of combination studies.
With which agent?
gantenerumab, if I heard it correctly. Emmanuel, if you put.
Yeah, sorry. You can skip it if you don't have an answer. It was apitegromab, myostatin.
Okay. Obviously, we don't have an answer to this one.
Okay. Thank you.
That means also most likely we have many anything planned at this point in time. I think the answer is given by the non-answer.
Okay.
I guess.
Okay. Did you want to ask your question?
It's the Scholar Rock enteropathy.
Exactly. That's the one. Yeah, sorry.
Sorry, I wasn't quite aware it had an INN yet. Yeah, this is an interesting mechanism. We do have an internal program targeting myostatin, actually a really good molecule that's in phase I trials right now. There's no firm plans yet, but certainly it's a mechanism that we think might be interesting as a potential combination partner for any of these therapies because it works via a different mode of action. We're looking at those data. It's still pretty early. I don't know, Kathryn, if you want to add anything on that.
I would just reiterate what you said, that it is an interesting possibility to be able to continue to grow the atrophied muscle of SMA patients after the motor neuron dysfunction has been addressed.
Thank you. Thank you. Thank you very much. Richard Vosser from J.P. Morgan, I open your line.
Hi. Thanks, Karl. Thanks, everyone. Just a question, firstly, looking at the JEWELFISH data by age, was there any benefit in younger patients, so stabilization in the overall population, any benefit if the patients were younger? Second question, on the stabilization of disease, just any sort of payer feedback on their positivity about that sort of level of benefit? Clearly, patients like it, as you say, but any level of feedback there. Just finally on the motor milestone benefits past 12 months, are you continuing to see beyond 12 months, I know it's early, but continuation of motor milestone gains in the RAINBOWFISH study? Thanks very much.
I can dispense with the first and the last pretty quickly, and then the payer feedback, maybe Simona can address. Again, we have not subdivided or done subgroup analysis on the exploratory efficacy of the JEWELFISH. In the RAINBOWFISH, we do not have the data yet on post 12 months.
Oh, yeah.
This is payer feedback on risdiplam, right?
Payer feedback on risdiplam for the stable-
Yes.
Stabilization of the disease. Yeah.
I think Kavita has probably the best handle on these things, so I just would suggest maybe she can provide the answer.
Yeah. Kavita, please. Yeah.
Yeah, no, for sure. I would say that you know from SMA Europe that patients are really excited about stabilization. 96, 97% of patients see stabilization as an outcome that they're very excited about. As it relates to payers, as these are early data, we haven't approached payers extensively. We do see coverage now in the U.S. where we're launched. We do see coverage in patients that are previously treated amongst U.S. payers.
Okay. Moving. Did that address your question, Richard?
Yeah. Thanks, Karl. Thanks very much.
Thank you. Next one would be Simon Baker. Simon, I open your line now.
Great. Thanks so much, Karl. A couple questions on JEWELFISH, really going back to Richard Emmanuel's questions. Do you have any data at this stage on efficacy by SMN2 copy number? If you don't have it now, will that data be presented when the trial's concluded? Just going back to slide 18, I was looking at the patient numbers there. I'm assuming those patient numbers have been impacted by missed appointments rather than dropouts. Can you confirm that there are still 165 patients in that study, i.e. 174 minus the nine that have dropped out? Thanks so much.
Your first question about SMN copy number, was that in reference to JEWELFISH or RAINBOWFISH?
JEWELFISH, yeah.
JEWELFISH.
JEWELFISH. No, we have not broken that down by copy number. In terms of the assessments of patients in the JEWELFISH, there were only nine withdrawals. However, you are right that there were many missed study visits because of COVID. For the MFM32, for example, there were 134 patients assayed for that.
Great. Thanks so much.
Yeah. Thank you. Michael Leuchten from UBS, I open your line. Michael?
Taking the same question backwards. Can you hear me fine?
Now we can hear you, yeah. Mm-hmm.
Taking the same question backwards. If you look at a doubling of the SMN, but you do not see a change in functional score, at what level would you have expected there to be a change in functional score? Is that doubling a number that you thought might have triggered that? If not, why not? Just because Karl invited a question, I'll sign this, Karl, for you. Given the change in the FDA stance to potential future approvals, does that make any difference in the way you think about trial programs from your perspective? Thank you.
Kathryn?
Yeah. I think I need a little clarification on the first question. Is the question, if we doubled the SMN protein level, would we have expected an improvement in function? Is that the question?
Michael? Maybe what we could do is we could maybe go for the Alzheimer's one. I could reopen your question later on, Michael, when the line is a bit more stable. Maybe, Paulo, you can go with the Alzheimer's one, please.
Yeah, of course. It is an interesting question for speculation, I would say. The decision by the FDA around aducanumab is obviously precedent-setting and opens up all sorts of new possibilities. It's the first time that a medicine is approved for a neurogenetic condition based on a surrogate endpoint, essentially on change on the biomarker with supportive clinical evidence. Of course, up until now, this has been a little bit the dream of a lot of us who've been working in this area, that you might be able
We seem to have an issue with the line for Yeah.
Maybe while Paulo is-
Maybe you can take it.
Maybe I can just take a little bit since Paulo and I tend to talk about these things quite a bit, right, as part of this.
Yeah, of course.
Maybe just, I think where Paulo had left it, this is an interesting point in time where potentially in neuroscience the ways of getting approval can potentially be based on surrogate, which is not an unknown path from the FDA, as we all know, right? It just has not happened in neuroscience so much. I think from our perspective, we're excited about this because that brings new potential medicines to patients faster. It is going to be important to make sure that the surrogates are clearly correlated with clinical outcomes so that we end up generating the right data short-term and long-term and be able to have the sustainable benefits to patients. We'll definitely be looking at these things ourselves in programs that make sense. I don't know if that answers the question, but it is an exciting time in neuroscience, I would say.
Yeah. It's also a bit difficult to comment on those things at the moment as we didn't have any contact with the FDA since approval of the aducanumab data. We take it now, let's say, take it from there. We will keep you updated as discussions evolve. What we have shared with investors in the meantime, unless we have now any other information for you, we would advise the market, let's say, to just go for the full line of a readout. At this point in time, that would be, let's say, prudent to do. If there is something else in the early and whatever, we keep you updated. Yeah. Our continuum update, I will read out in 2022. This anyway, not too long time out from here. Just to give you a bit of perspective where we stand at the moment.
Paulo, can I try to answer Michael's first part of his question?
Sure. No, please. Yeah.
There may be a nuance to that that I missed, I think what he was asking, with the doubling of SMN protein, would we have expected an improvement in strength rather than just stabilization. We saw a doubling of SMN protein levels in all the Fish studies. What is different about the Duchenne fish is that there are patients who have severe weakness, low muscle mass, contractures, severe scoliosis, and those all play a role in the response to treatment. No, I don't necessarily think that a very severe individual who is treated with risdiplam will necessarily have the same response as a younger, less affected individual.
Yeah. Hi, Karl. Sorry, I'm back. My laptop decided to die on me suddenly.
Gosh. Yeah, that happens sometimes in this new world, huh?
I reckon.
Michael, I hope you could Yeah, I see that you're at a different place now.
Yeah.
That's fine. No worries, man. Michael, I hope we could address your questions. I would go on to with Jo Walton. Joe, I open your line.
Thank you. It's Jo Walton from Credit Suisse. I guess my question is along the same lines. I'm looking at slide 17. Forgive my ignorance here, but you've managed to double the level of SMA protein levels. How close do you get then to a normal, healthy child? Secondly, given that you appear to be able to double the protein levels in those patients who've had prior treatment with ZOLGENSMA, isn't this the ideal slide to show that you should be using dual treatment? If you can take ZOLGENSMA, because presumably these were only the younger end of the range who were able to take that in itself must improve the protein, then on top of that, you're doing it again. Isn't that an absolute shoo-in for dual treatment?
Unfortunately, it's a little more complicated than that in that our SMN2 protein level is measured in the blood because risdiplam is delivered systemically and affects multiple organs. Other treatment options such as ZOLGENSMA and nusinersen have either targeted to CNS or muscle or a different route of administration that neither one of those would show up as SMN2 protein levels in the blood. The reason that we use SMN protein level in the blood is that it is a non-invasive way for us to measure, to have a biomarker of efficacy of risdiplam. We don't need to do a lumbar puncture, for example, to look at SMN protein levels in the cerebrospinal fluid. Our preclinical data has suggested that SMN levels in the blood are highly correlated to that in the CSF, to brain, to muscle.
Can I just ask if there's any view from the regulators or the payers about the concept of if you've taken the Zolgensma approach, are you finding that patients are finding it difficult to then add this on top? Or such a devastating disease that the payers are likely to accept dual therapy?
I'm happy to address that, Jo Walton, I think it's a great question from a payer lens. As I said previously, in the U.S., the first market that we've launched, we have seen patients that were given ZOLGENSMA gene therapy being treated with risdiplam. There is some access in the U.S. for this patient population. As we see more data and now hopefully with JEWELFISH, there's even greater confidence in the safety that risdiplam can provide in this population.
Thank you.
There is a question from the chat, which I'll just read to you because I think, Kavita, this is going to you. The question is from Diana Na, and she was asking about the Evrysdi uptake so far in the U.S. Could you perhaps provide more color where patients are mainly switching from? Are they more coming from SPINRAZA? Are they coming more from ZOLGENSMA? In which subtype are you seeing Evrysdi largely being prescribed? Basically, if you could give us an update on the U.S. market dynamics. She was also asking about the Europe approval, recent approval, if you could give us an update on where we stand at the moment with the first signs of the launch.
For sure. I'll speak to the U.S. first, and we're really happy with what's happened in the U.S. We see a really strong uptake of risdiplam across a broad range of patients. Similar to in our trials, where we've been studying a broad range of patients, we're seeing that in the market play out as well. What we're seeing is similar to what you see in the prevalence of Type 1, two, three. 25% of our patients are Type 1, 50% are Type 2, and the other 25 are Type 3. You asked about what does it look like in terms of treatment-naive versus previously treated. We see about a third of our patients are treatment-naive.
We see about two-thirds that are previously treated with both Spinraza as well as Zolgensma, more switched on the Spinraza side, as Zolgensma is still early in terms of the number of patients that are on gene therapy today in the U.S. Overall, very strong uptake. We are the fastest, I would say, DMT folks in this market as the uptake we've seen thus far with the DMT in the U.S. market. We're seeing very similar performance now in Europe as well. The most recent approval in March, our first country to launch is Germany. What we're seeing there is also very strong uptake in Germany, similar as we're seeing in the U.S. Thus far, over 200 patients have been treated in Germany within 24 hours of approval.
We got a patient on product, which is fantastic and shows you that it's accessible to those patients in that market. Now we're seeing six weeks out, we're already over 15% market share. Again, very strong performance in Germany, and as the other markets get up and running, we'll be sure to share more.
Very good. Thanks a lot for the update. Next one would be Stephen Scala from Cowen. Stephen, I opened your line.
Hi, can you hear me?
Yeah. We can hear you, yeah.
Two questions. Actually they're both on Alzheimer's. The answer to the gantenerumab question had all the appropriate conservativism, but there has been a major change in the landscape, and Roche is best positioned to take advantage. Perhaps you can lay out the range of possible alternative pathways to approval that Roche is now exploring, and would one of them include a possible approval of gantenerumab this year? Secondly, initial Roche data on tau was disappointing, but Roche has another candidate in development. Several competitors are following. Does Roche think tau is a failed target, or are you optimistic that different agents with different target engagement could still show benefit? Thank you.
The good news is, Paulo, that you are back online. I would say we give points to you, huh?
That sounds good, Karl.
It's a good
challenging question. I don't want to evade it. We are certainly looking at the full range of options right now, okay? The extremes, if you want, one of them is obviously a wait for the data readout from our GRADUATE program, which should be coming second half of 2022. That obviously is a full data package, includes all the safety, all the efficacy, all the biomarkers, everything else. That is still our base plan, by the way. That's still what we're doing. We are looking at all the other options. The other extreme range of the options is considering something like an accelerated approval based on biomarker evidence.
Of course, we don't know what that looks like, and this would require some sort of dialogue with the FDA, with the agencies to find out what their, say, standards would they want to have. It's something that, yeah, we're keeping open as an option for sure. Again, our base case continues to be that we want to have a full, robust data set that includes the clinical data, because that is what in the long term will matter to physicians and to patients. Of course, we understand it's a brave new world since last week, and we're not blind to the multiple alternatives here.
On the tau. Sorry?
On the tau?
Yeah.
Regarding the question on tau. Yeah, we reported out the data from our TAURIEL study, which was the first-ever attempt of using a monoclonal antibody against tau to try and have an impact on cognition and function. As you mentioned, the results were disappointing. There are a number of open questions, even regarding that trial, and also regarding another trial with the same antibody called LAURIET, which is being studied in moderate Alzheimer's patients. The questions are around target engagement. We're still looking at our biomarker data to see whether we had enough drug on target and if there's any correlation with that. Secondly, we really don't know what the best population is to try these drugs in. Of course, with amyloid, the general mantra has been that the earlier, the better.
It is really something we've learned along the years, and for tau, we're just in the beginning of that journey. Regarding it being a failed target, I think it'd be incredibly premature to say that based on the evidence of one single phase II study with one monoclonal antibody targeting one of the epitopes. We are looking at other epitopes on tau. We have other programs looking at tau. I think generally, to answer your question, tau is, without a doubt, at least as far as I'm concerned, a super important target for Alzheimer's first and neurodegenerative conditions broadly. Yeah. We're still very hopeful about that.
Okay.
If you could just continue here, I have 1 more from Marcus Selvig goes into the same direction. If you could maybe talk about the advantages of any potential challenges of a subcutaneous administration approach with gantenerumab versus the IV aducanumab or Lilly's compound?
I'm wondering if maybe Simona and I can share this one because I can speak from a physician-patient standpoint. Building the 5G capacity is going to be a challenge necessarily, and obviously in terms of convenience for patients, especially patients who are usually older and more incapacitated and need to be accompanied to visit, et cetera. Being able to administer at home, whether it's self-administration or administration by a caregiver or by a nurse, I think it's going to be very relevant clinically, right?
We do have data showing, actually a lot of data showing that it's safe, it's well-tolerated, you get the same exposure. Provided the data looks robust, I'd see it as a big advantage, especially for such a big population. We're not talking about the rare disease with a few 100 patients. We're talking about millions of patients, but potentially globally. Yeah, I'd say that's a big advantage. Maybe, Simona, you want to add comments from your side?
Yeah, just continuing where you are. For me, in this particular disease, because the prevalence is so high that I think finding ways to bring these patients out of the hospital for treatment, I think is really important. Also, given the disease and the caregiver burden here, I think that's the other aspect that brings value to alternative ways to administer and to continue to have appropriate compliance. I think to me, the differentiation on the administration side, I think is really important for patients and for the family. I see that as a big advantage for us.
Thank you. We do have 5 more minutes, and we have 2 more questions in the line. The first one is from Peter Welford. Peter, I open your line from Jefferies.
Hi. Thanks very much for taking my questions. I've really got just two. I'm basically still on the broader neurodegenerative area. Firstly, I think it was mentioned by Paulo or Simona, I can't remember, that there are a number of surrogates that are well-established. I'm curious to know which surrogates, in your view, are well-established in neuro as being correlated to clinical benefit, and therefore could now be considered surrogates for an accelerated approval. Secondly, I'd love to know any comment that Roche may have on PET scans for Alzheimer's with regards to, not so much thinking clinical trials, but more your view on how that is evolving and the availability of that in the real world. Thank you.
Before you answer the question, Paulo, I guess I'll just come to you. Michael Leuchten just was asking a similar question in the chat. I just wanted to complete the line of questions. Paulo, please. Paulo, you're on mute.
I'm sorry. There's a regulatory concept of surrogacy, which requires a certain level of evidence, and obviously that the health authority declares it as a surrogate. Amyloid is the only one so far that has been declared as a surrogate, meaning that you can take that to substitute for a clinical endpoint and get approval on, in this case, accelerated approval on. Okay. Scientifically, there are many other surrogates that have quite extensive evidence. For example, tau levels in neurodegeneration are a well-known marker of axonal loss. Neurofilament light chain in MS and in other conditions are a well-known marker that is, again, associated with progression with neuronal loss.
Some of the imaging markers that we see, whether those are brain atrophy or hippocampal volume or ventricular volume, they've never migrated, if you want, to the level of surrogacy that a health authority would say, "I'll give you approval based on this evidence." For example, even in neuromuscular disorders, the precedent of using the expression of dystrophin in Duchenne for the exon skipping is essentially a surrogate which has been used for an approval, at least in the U.S. Now, one can argue, and I think there are legitimate doubts and questions about the value of all these surrogates and how much they do correlate with clinical evidence.
I think the general point for neurodegenerative conditions has been that one of the key problems that we've had as a field in terms of making progress is the fact that we need very long, very large studies using endpoints which have a very small signal-to-noise ratio because of just the heterogeneity in these patients. Having surrogates that one can base, let's say, either an approval on or a development on that are recognized by health authorities is or could be a really big development for all of us for this field. Okay. The second question around PET scanning. While it's certainly becoming more prevalent or more available for a variety of patients, it's still pretty much reserved, though, to tertiary healthcare centers because it requires pretty advanced technology, right.
It's never going to be as widespread, I would imagine, at least in the foreseeable future, as CT scanning or even MRI scanning. It's always going to be limited just because you need to have the ability to manufacture and distribute the radionucleotides pretty fast. For, again, millions of patients needing a diagnosis or qualification via PET, that is going to be a challenge. That's actually one of the reasons why from the beginning, we developed a CSF diagnostic that could be used and is being used in our GRADUATE program as the eligibility criteria for treatment. Again, CSF testing is a much more widely spread technology that can be easily done. Now we have actually a diagnostic which got breakthrough designation by the FDA and is approved as a standalone diagnostic. Anybody can use that.
I do think for a broader-based population screening, those types of tests are going to be more and more relevant.
Simona, anything to add from your side or?
No, I think I just said earlier, I think that was probably me when I said that we are excited about the possibility, that this approach opens not only for in Alzheimer's disease but in other diseases. Since we are committed to neuroscience at Roche, I think that obviously is something that we're going to be looking at across, at the same time, making sure that we have the right science supporting it. Which ends up being important at the end to show the clinical outcomes. That's what matters to patients and to doctors and to payers. I think it's important to do the whole package at some point or on the way, but really do take advantage of this potential opportunity because it's not so easy to get to that clinical data. It takes a long time.
Absolutely. Last one will be Sachin. I open your line from Merrill Lynch . Please.
Thanks for taking my questions. I have a few just quick ones on Alzheimer's again, if I may. You've mentioned you're pending a meeting with the FDA. Have you requested that meeting as yet, and do you have any timelines in mind? Secondly, Paulo, you mentioned 1 range as a potential accelerated file on biomarker. I wonder if I could just explore that further. What biomarker data would that be? Is that the Open RoAD data which contains some amyloid reduction at the highest dose rather than the phase III SCarlet RoAD and Marguerite RoAD data? If you could just comment on how you look at the quality of that data versus the amyloid reduction data that Biogen has in.
The reason I ask the question, some of the physician feedback that we've had on that data is very strong given that you're getting amyloid negativity in a high percentage of patients. The third question is, as you discuss with the FDA, one assumes that they're open to some sort of proposal. I ask the question, as you think about the Brainshuttle Ganta program, which is in the sort of sweet spot of potentially benefiting here. I'm sure you've discussed this internally, but what sort of proposal or thoughts do you have around an accelerated sort of phase II/III program when you think about level of amyloid reduction, number of patients, and what cognition data would be given at this accelerated stage? Apologies for those questions, but would love the thoughts.
Yeah. Thanks, Sachin. I think you may be over-interpreting a little bit of what I said, because I said we are thinking about having meetings with the FDA, right? We've not booked anything, we're not on a flight to Washington. There's nothing like that. Of course, these are delicate conversations that we want to make sure to respect the regulators' time and viewpoints as well. We are considering right now. We have the range of options, we're thinking about them. Anything else is speculation right now. Regarding biomarker data, there's lots of data that we've been showing throughout the years and which is public. As you mentioned, Marguerite RoAD, SCarlet RoAD data, now Open RoAD data.
We think there's very interesting data there showing amyloid negativity after not so long of a treatment period and after 3 years, about 80% of people being amyloid negative. There's a dose-response relationship. We've shown a lot of our modeling data that underlies our dose predictions for the GRADUATE studies. There's quite some data which is robust and public. We've not had any conversations with the FDA, and therefore, we don't really know what type of data, if we were to explore that option, they would be interested in. I would imagine that data, which is public, might be a part of it. I don't know if it would be enough or if there would be requirements for, let's say, more safety data because it's a new material. It's G4, the RoAD studies were done with G3. There's a number of technical complications, right?
Again, if we were to approach the agencies with this, we would be approaching it in the spirit of full openness and collaboration, because obviously we appreciate that it's a brand new world for them as well. Therefore, we want essentially to explore the option of working together to see what could be possible, right? I do think that it is a very interesting time right now because of the acceptance of amyloid biomarkers as a surrogate, potentially for clinical outcomes. It does beg the question, what type of data would be required, right? Again, we're entering into this conversation with open hearts and open minds, knowing that this is going to be something, if we explore it will take a lot of collaboration between the agency and ourselves and any sponsor by that matter.
Yeah, thanks a lot. Yeah, thanks for your interest in Roche. I think what we could present to you today is really very exciting new data for Evrysdi. Making good enroll in all markets where it's already a bit established, like in the United States, but also the first signs and signals in Europe with a 15% market share in a very short period of time actually speaks for the drug, speaks for the acceptance in the market. There is clear evidence of best in class for type 1, type 2, and type 3 data building here more and more. We will hear more about the next weeks and months on it. I'm not surprised that we had a lot of questions on Alzheimer's, I have to say. As I said before, there is so much we can say at this point in time.
It's a bit of a limitation on our side as well. I think you will understand it, but clearly the field is moving more fast than it would have expected 2, 3 weeks ago. That is actually encouraging. That brings me to a big thank to Kathryn Wagner for presenting the risdiplam data. Thanks to Kavita Patel, thanks to Simona, thanks to Paulo Fontoura. I also wanted to thank Jared from our team for taking the lead on that call, putting the Q&A together and the slides and the storyline, and also Melanie for helping with the organization. Wishing all of you a nice day. It was a pleasure having you here. Thanks for your interest in Roche, and all the best to you. Bye-bye.