okay perfect thank you hello everyone and Welcome to our webinar today my name is do 11 and I am the senior director for uh patient education and I'm sorry I'm trying to do want um I'm going to share my slides one seconds sorry about that they closed no worries take your time let me chair no if I'm going ask you to share the slides because I'm do not have them coming up I'm gonna I'm G to send it to you really quick actually let me send it to you Mike because you seem to have permissions that I do not certainly sorry about that everyone one second we'll be ready not a problem tech technology issues [Music] happen do you think I'll be able to open the slides that I have ready to go should I test them real quick to make sure you will you will you should be you should be I'm gonna test it go ahead if you want to pull yours up you go ahead you know what I'm just gonna read my slides I'm gonna I'm just gonna go ahead and read my slides and you keep your slides up so I am gonna introduce Dr Wolf today um Dr Wolf will be speaking to us on a new treatment from M for M Dr Wolf is the chair of the Department of Neurology at the University of Buffalo school of medicine and biomed Sciences the State University of New York he is also the Dr Bob and Jean Smith Foundation distinguished chair in NE neuromuscular disease research his interests in neuromuscular medicine are wide but have mainly focused on myasia gravis and other disorders of neuromuscular transmission as well as peripheral neuropathies he is the board he is board certified both in neurology and neuromuscular medicine he is also B board certified in neurophysiology and performs electromyography and nerve conduction studies and monitors intraoperative evoked potentials for spine surgeries and other operative cases he remains actively involved in training of younger Physicians and has directed neuromuscular medicine and the clinical neurophysiology Fellowship and neurology residency training programs we do want to thank our sponsors today for the series our SP National presenting sponsors are alexion argic and UCB and our national sponsors are Horizon andan and neurosciences so Dr Wolf we are ready for you and you can go ahead okay great and I just want to make sure somebody give me a thumbs up DOA give me a thumbs up if you can see my slides you do okay and people can hear me as well great okay well I'd like to thank DOA thank the me gravis Foundation of America it's just a great organization um I was um communicating earlier today with Sam Masterson on some work that we need to do next year but uh you know an organization that really focuses on my medog gravis and closely related conditions and um you know these seminars I think are great for patients and their families and for us too because we get to hear from you and rethink things sometimes but I'm going to talk about not the newest now but nearly the newest agent that's been approved from Mya gravis and it's called Rigo it's Ranna lism no which is a little bit hard to say people often will just shorten Rosano lisab to rosb just so you know the reason I'm saying it's nearly the newest is because honestly in the last week I think it was four days ago um you CB the company here also had another drug approved for Myas grav all these five drugs that are approved are for generalized mastini gravis there's slight differences in the approvals though and I'll get to that specifically with Rosano Luisa moli with Rigo because it's the only one that's approved also in musk myasthenia gravis and we'll go through some of that data but anyway this was recently approved earlier this year um it is the second agent with this particular me mechanism of action we'll get to called fcrn antagonism so I hope that's a good start there's only 32 slides I'm going to try to get through them as fast as I can so can I can answer a lot of questions all right so this is the first FDA proof treatment is I alluded to a moment ago for both acetal Coline receptor anybody positive mg which is the majority of generalized mg but also anti-musk anybody positive mg okay it's a subcutaneous infusion so it does involve a needle It's weekly for generally six week Cycles similar to how other fcrn antagonists have been approved they're these cycles of therapy and it's given weekly it's a single needle okay and we'll get to the safety stuff that's at the bottom of the slide later okay so what is it indicated for it is indicated for um uh uh adults over age 18 basically with generalized myasthenia gravis again either receptor antibody positive or musk antibody positive okay realize this is an an immunotherapy all of our immunotherapies can potentially increase the risk of infection this can also cause aseptic menitis so what's some some just to I think many of you on the call are familiar with myasthenia gravis um um but just a few disease State slides to get us started it is an autoimmune disease what does that mean it means that the immune system is attacking itself and in fact mytina gravis is one of the better understood autoimmune disorders we know exactly what's being attacked in most cases as far as a specific antigen for instance the ocine receptor or musk uh which is also on the muscle membrane it's chronic this is a lifelong potential disease it's a chronic disease immune system that's the system mainly composed of humeral and cellular factors that protect us from infection and disease as well for instance cancer our immune system helps fight off uh malignancy as well so it's very important but it's arai in patients with Myasthenia or in patients with lupus or in patients with autoimmune thyroid disease or in patients with rheumatoid arthritis but myasia gravis is one of our better understood autoimmune diseases not that it's the most common but it's pretty well understood generaliz myasthenia gravis there really two major clinical types we have generalized disease and all the five drugs have only been improved in generalized disease I just want to say that UPF front there's also pure ocular mg it's less common most mg is generalized if not initially over time usually within the first year or two generalized symptoms do appear what does that look like muscle weakness and fatigue but it can involve things like chewing or breathing or arm and leg weakness May making climbing stairs or even shampooing your hair or brushing your teeth challenging and I think you all know it is our classic fatiguing disease fatigue can occur in many different neurom in many neurologic diseases such as Parkinson's disease I mentioned this before somewhere around 90 95% of people who have generalized mg are either going to have acetool receptor or musk antibodies the remainder have perhaps lrp4 which is very rare that's a very r antibody or are just simply Ser negative where we cannot detect a specific antibody despite a bunch of different blood tests now realize in addition to receptor antibodies musk antibodies we've seen antibodies again I mentioned to lrp4 quite rare there's a few others that are thrown in there but the main ones we could commercially test for are receptor antibodies that's acetyl receptor ACR the musk and lrp4 okay this is our neuromuscular Junction on on the left I don't know if you can see my uh Arrow I bet not but you can see the nerve at the top in blue you can see the muscle membrane and the bottom and yellow with those nice folds those kind of crevices the little black dots are The receptors okay uh um and the little asteris bluish things coming out of the nerve that's neurotransmitter here we're specifically talking about acetyl Coline okay is the neurotransmitter at the neuromuscular Junction this is what it looks like normally if you impair neuromuscular transmission this sequence of events going from nerve to muscle you will lead to weakness okay and see are some important terms on the right again the neuromuscular Junction is a connection between the nerve and the muscle if you look at the muscle kind of like a light bulb the nerve is kind of like the wire that feeds that light bulb and the light bulb going on would be contraction of our muscles so we can generate strength okay neurotransmitter is a chemical signal that carries information from the nerve cells again in this situation it's aceto Coline and The receptors are proteins in cells usually on the surface though that actually receive the chemical signals okay and here it's primarily the acetylcholine receptor now realize aceto Coline does not directly interact with musk but musk does interact with something else through another receptor called uh a nerve derived dagrin and it's crucially important that sequence of events going from um agin to lrp4 to uh musk that enables proper scaffolding and proper formation of the neuromuscular Junction on the muscle side the endplate is what we call it so if you interfere with that musk related phenomenon and sequence of events Cascade of events you will also mess up neuromuscular transmission I just want to mention that because there's not really a great figure for that here are any antibodies these could be to the aceto receptor or to musk the antibodies are these reddish why things why are they wise because that's what they actually look like on high magnification um they look like y structures there's an FC and Fab PS I don't want to get into that but what I want to get into is if you look at the two y's on the left here the one furthest on the left that could be an antibody that's simply just blocking the acetylcholine receptor itself and preventing proper uh uh Ion transmission so we can excite the muscle membrane it's sodium entry but I don't want to get too far into the weeds here the one in the middle you can sort of see it uh if you can Crosslink two acetylcholine receptors two of those dots one way that cocoline receptor antibodies cause the disease is they actually reduce the number of receptors if you cross link two of them they actually will internalize and go into the muscle okay and so you have fewer cetal choline receptors there to help us transmit the signal from the nerve to the muscle antibodies on the right it's a part of our immune system when acting normally they protect us from foreign substances such as viruses and bacteria when you get a vaccine you're hoping to build up antibodies like when we get the covid-19 vaccine or the flu vaccine uh for that matter now realize the therapies most of these not all of the approved therapies but most of them are also antibodies they're monoclonal synthesized antibodies to do certain things and we'll get to that in a little bit okay so how does it work we got to it right away how does this work okay here we see again our antibodies and let's pretend that this antibody is made to the acetylcholine receptor okay the fcrn mechanism that's also known as the neonatal FC receptor it's on many cells But it includes endothelial cells the cells that basically line our blood vessels this mechanism allows I molecules to persist for weeks about three to four weeks in our body okay if this antibody connects with that fish that F looking uh molecule which is in yellow if it makes a good connection and binds it will get recycled the whole process that we're doing with fcrn antagonism with a drug like Rigo is to block that binding to prevent The Binding of that orange reddish antibody to the yellow neonatal FC receptor because if we block that binding what we'll end up with is at the bottom here of this cell figure the circle you will degrade if there's no binding that antibody will be degraded and that's a good thing if we can degrade disease causing antibodies we'll have less of them and we'll have potential Improvement in the disease State and that's what we've seen with the trials of these types of Agents okay now why I want to just mention IGG specifically is because every single form of Myas gravis that we have identified that is connected to an antibody it is an IGG antibody okay it's an IGG antibody realize this system has nothing to do with IG or IGA or IG it's specific for the IGG system okay because but I'll just blow this in as an aside that is why the Half Lives the survival of these other I globulin molecules that also can help us fight infections and are involved with allergies and things like that their half lives are days not weeks like for IGG so now moving on Rigo that green again it looks like an anybody because it is it looks like a y because it is it's blocking that interaction of the red and the yellow and because we don't have the interaction of the red and the yellow the antibodies are broken down okay now yes you may be thinking well does that break down other IGG molecules it does this is pretty much a class effect across IGG 1 2 three and four that's why there is a susceptibility of potential infection because it's also removing Iggs that may be doing good the on to acline receptor ANB to acline receptors are not doing good but there's a lot of Iggs that are doing good and it does reduce those as well not 100% but somewhere in the 70 80% range okay let's move on so what were the results with the actual trial and so you know trials are complex this was a complex trial like most patients uh 200 patients were randomized to either Placebo or 7 milligrams per kilogram or 10 milligrams per kilogram of the active drug in equal aliquat so a third in each so he ended up with about 66 67 patients in each group and again I as I mentioned before they received one dose every week for for 6 weeks and then they underwent an observation period of up to eight weeks to see how they were doing and patients could be retreated with a subsequent cycle okay beyond that period of time but the primary outcome was done at a day 42 after that initial cycle of six weeks 6 time 7 is 42 it was actually day 43 but anyway basically six weeks okay and it included both receptor antibody and musk antibody positive patients What was seen significant Improvement in the mgl that is an8 item scale I wrote the first paper on the mgl back in 1999 a quarter of a century ago now but anyway it is the outcome measure that the FDA has used as the primary outcome for all of these different drug approvals and as you can see there the details are minus 3.4 points with the active drug versus 08 only 0.8 not even a full point on the B CBO and that was statistically significant and just to give you an idea even a two-point drop on the mgl is considered of some clinical significance for patients okay this rapid Improvement was definitely seen by the end of six weeks but even as early as one week after the first dose some patients had Improvement that quickly okay and what you can see at the bottom is the proportion of patients on the two different doses um um compared to Placebo it was out uh 35% of patients on the lower dose 38% on the higher dose compared to just 24% of patients on Placebo who had a significant Improvement okay uh uh um uh based on mg-adl all right what is the mgl scill again I mentioned it's eight categories it assesses ocular function breathing talking chewing and so forth It's it's real easy to do it takes a minute and a half after you're used to it it doesn't matter if patients fill it out on their own or if it's driven by a health care provider um there's a couple studies that show that but um I actually follow it routinely in my clinic okay uh and then it's also used as I mentioned as a primary outcome measure all right now this is other data from the clinical trial so up to 72% of patients responded to treatment okay um so not 100% but it was basically three orders and that was based on at least a two-point Improvement again I mentioned that two-point threshold as being clinically uh significant clinically meaningful if you will on that mg ADL score a two-point drop or greater is considered clinically meaningful and we got that in three quarters of the patients yes it was seen in Placebo as well 31% but that was statistically significant favoring the Rigo as far as the proportion of pages responded and then here's the must story again I mentioned there were a dozen 12 participants and all of the patients with mus gy bodies did improve based on the mg ADL score all 12 out of 12 a rare form of mg but still you know it's it's nice to have an approved agent for the first time in the musk population this is the very first one it's always crucial in addition to looking at clinical efficacy to look at side effects I mentioned before infections can be of concern because again we're reducing IG globally here and IGG is important in fighting infections you can see yeah there was a slightly increased uh percentage of patients on rigga who had say an upper respiratory uh tract infection you can see yeah diarrhea was somewhat more common fever more common other things were really quite uncommon 10% or less and not a really marked difference in what you saw on Placebo so even on Placebo 19% of patients had some infection it was just 4% higher on rtia but it is something that we have to monitor and and and and always be mindful of both the doctors and patients and your families need to be mindful that there is that potential risk there's no vaccination that is required before this agent if you were wondering about that um so Rigo may increas increase the risk of infection as I mentioned before I won't go through that any further a septic menitis what is that these patients look sick they don't have a actual bacterial viral cause of menitis that's why it's called aseptic it's a chemical type menitis but they can look very sick even have some fever a stiff neck like you get with bacterial menitis it is possible I haven't seen it with this class of Agents but it is potentially possible and has been reported just excuse me for one second hypers sensitivity reactions swelling and rash that can occur with just about any infused medication there are potential allergic reactions and so forth so those need to be kept kept in mind as well um if you're planning to become pregnant or are pregnant so um the fcrn agents uh uh The fcrn receptors were actually first described in other tissues like the mamory glands and also in the uh um um in the placenta to actually transfer IGG to make sure it gets transferred over to the neonate or the fetus and so if you are pregnant uh these types of Agents can interfere with those types of processes which would not be advantageous for the baby so you need to let uh um uh um your healthc care provider know plus the true safety of these agents in pregnancy is not clear yet hopefully over time we'll we'll we'll be able to uh uh determine that with greater uh uh Clarity okay um you need to talk about other medications that you might be on the most common side effects again were headache and infections and diarrhea okay so what to exp expect with Rigo as I already mentioned it is a um infusion but done subcutaneously a single needle is inserted just under the surface of the skin it's generally done in the lower abdomen area you do have to get monitored it has to be done in some kind of Health Care setting uh with a health care professional that's how so far these subq infusions not just for this agent but for other agents is being done at least in the mg theater okay but it's pretty quick and again it's weekly for six weeks so there it is the first treatment cycle of six doses once weekly and then you're sort of seeing how patients look okay and what you can see here in a long-term extension study okay in Gray inside that box the minimum length of time between the start of treatment Cycles was nine weeks okay so that would have been about three weeks and after the six dose weekly cycle but other patients can go quite a bit longer okay and do realize as a label says the safety of starting later cycle sooner than 63 days from the start from that very first infusion of the prior cycle it's not established okay so I don't think you're going to see doctors really you know doing this at least from the information that we have right now in any kind of cycle faster than three weeks after finishing the prior cycle that's the main message to get across here most people may require repeated cycles of retigo to manage their GMG symptoms these agents don't last forever you will see the IGG levels and even the acetool receptor antibody uh levels start coming back to Baseline increasing several weeks after those cycle start so the the the supposition is you know repeated dosing is going to be needed in some fashion but again how frequently those Cycles have to be repeated that's going to vary and will have to be individualized per patient okay so it's important to track your GMG symptoms that may return during breaks from treatment uh be sure to discuss them and then you know make plans and decide how you're going to schedule this that's going to be a two-way street between the doctor or supportive staff in the doctor's clinic and you and you okay to exactly figure out how many cycles are going to be given say in a year's time okay but nice in a way even though there's some uncertainty about that it's nice in a way because it really can be individualized that so you can actually gauge that and determine that over time depending on patients responses I already mentioned about infection risk if you have an active infection you should hold off before you give this medication and treat that infection I would not feel comfortable giving this agent or really any of the other approved agents at this point in time to a woman who is pregnant onward so this is the name name of a support system uh that is provided by the uh uh uh um by the uh industry by by UCB to help uh patients and there's a uh um website there UCB onward.com pretty easy to remember again I'll repeat it UCB onward.com there's also that phone number there um obviously you can go online at any point in time the calls have to be Monday through Friday dur during generally uh during uh uh business hours but um what does onward have a medically trained coordinator tools and resources to help you get started or to continue therapy insurance coverage reviews and so forth and guidance and symptom tracking uh and ongoing treatment support it's all built in into this uh uh support system that uh is sponsored by uh UCB so how do you talk to your doctor excuse me just for one moment um you know I often get a question from patients especially early on in their disease course with mg what should I look for if I'm getting worse sometimes it's the same symptoms that you presented with sometimes it could be slightly different symptoms and so it's important to have some appreciation of the different types of things that can occur in Myasthenia grais and that's why handing out information from the mein grais Foundation of America where they have pamphlets and online materials that described mg is really really important also the drugs that you should avoid when you have Myasthenia grav mgfa has all those types of resources and they're easily accessible and they are free okay um how will I know if any new symptoms are related the GMG it can be difficult if it's just a fatigue element for instance and uh the patient may also have congestive heart failure for instance which can cause fatigue or thyroid issues that can cause fatigue it can be somewhat difficult sometimes even the doctors are not completely sure but it's always best to check in with the doctors their nursing staff and so forth if you're worried um what do I need to consider as far as what the subcutaneous infusions are like yeah you know you may get some tenderness right in that area a little bit of a inflammatory response where you where you get a subcon continuous infusion during a treatment cycle you want to keep track of any side effects and share them with the doctor um you know what track how you're doing you may do that from the mgl it's easy to do that on your own or just keeping a calendar you know after those six weeks are over do you notice some of the symptoms that you had before even some new symptoms arising let us know because that's going to help us guide how we repeat those cycles and again the Cycles are six weeks I I I don't anticipate much short drifting cycle saying just three weeks right now it's the Cycles are are are designed to be a six week cycle so here's sort of a summary slide again rigga reduced generalized my gravis symptoms based on the mgl significantly it also improved objective measures of me to gravis say from the quantitative mg score that's a 13 itm score that's also tracked in these trials it works by targeting neonatal FC receptors when neonatal FC receptors are not blocked that makes IGG have a sustained lifespan in our circulation a period of about 20 to 25 days three weeks or a little bit longer but using antagonist will make those IG molecules will degrade them again in like isomes in the cells that's where they end up getting uh navigating towards if that interaction between the IGG and the neonatal fcrn receptor is blocked okay and that's what this drug and Other Drugs in the same class are designed to do and again it's administered quite quickly somewhere around 15 minutes okay well we thank you very much for your time and thank you to UCB for this presentation