Brian R. Wood, MD – Find this and other presentations at
Welcome to nwa e.t.c project echo i’m kent andrew and i’d like to turn it over to david spock to introduce our new medical director and speaker today great we’ll welcome this afternoon we’re going to have brian wood kick off his tenure here as the new director and he’s going to start us off with the new single dose tablet stride build he’s going to give us an
Update and we’ll get in some cases thanks david so today we are going to talk about stri bill which is the new single tablet regimen we’ve been referring to for months as the quad pill it is now officially named stri build it was fda approved on august the 27th and it is the newest in a series of single tablet regimens that combines elevate egg revere cove assist
At two na fear and emtricitabine so it’s a one pill daily regimen it’s slightly smaller in size than a triplet not as small in size as com clara so think about those patients who have difficulty swallowing complains the smallest of the single tablet regimens stri build should be taken with food and two hours apart from any antacids that’s because of the elbaite
Tegra veer component the absorption is affected by antacid so that’s important to remember and acid use isn’t a contraindication like with complet it must be separated so important for counseling patients and the individual components there are two novel components here el by tiger beer and coke assist at of a tiger beer is the new once-daily integrates inhibitor
In stri build it’s 150 milligrams and cobus estat is the new cyp3a4 inhibitor also 150 milligrams in stri build unlike ratana beer it has no hiv activity and we’ll talk a little bit later about some of the side effects and how they compare to ratana beer and then the two nrti components were familiar with emptor cytokine and to na fear i’d like to talk about the
Two main studies that led up to its approval the first being study 102 which was a phase 3 study that compared stri build to a triplet or a fabrice with – not fear and emtricitabine and this was a phase three study in treatment naive adults there were seven hundred total which were stratified to either stri build or a trip lows about 350 in each arm and they
Also got a matching placebo patients had to have normal renal function and a baseline hiv rna above 5000 copies about a third had a baseline hiv rna above a hundred thousand that couldn’t have an aids condition of previous 30 days and the two arms were very equally matched one main criticism of this was that there were not many women in either arm only about 10%
In either arm otherwise they were very equally balanced and i’m going to dive right into the results here and what you see on the left is the percentage who achieved their main end point which was an hiv rna less than 50 copies at 48 weeks and you can see in the green is the elbow tagger kopassus tat or stri billed arm and in the blue is the triple a’ or a fabrice
Arm and these were not statistically different so this was non inferior non-inferiority endpoint and when broken down by viral load strata you can see these again are not inferior or not significantly different so unlike the single tablet regimen completa dry build really is not inferior at all viral load endpoints when looking at the main adverse events with stri
Build so this is all advert reitman emergent adverse events that were greater than 10 percent looking first at the elbow tag roberto busa stat or stri build arm first thing to note here is the most common side effects with dry build which mostly are gastrointestinal so diarrhea nausea also about 15% abnormal dreams which i thought was interesting and then headache
Fatigue but primarily gastrointestinal and then the one that was most significantly different than a trip low was nausea the side effects that were more significantly associated with a triple a’ were insomnia dizzy and rash not surprisingly study 103 was the other phase 3 study in treatment 90 patients which was a very similar design about 700 patients stratified
To either alva tigger albeit egg revere kobus estat or truvada with boosted a disease anna bear again very equally matched again not very many women in these in these arms and again you can see that stride was non inferior when compared to terada with boosted etta’s anna bear and this held true at all viral loads and when we look at the treatment emergent adverse
Events here again with elbow terekhova cyst at primarily gi side effects so we really haven’t improved here over our ritonavir based regimen and the only side effect that was more common in the out of zone of your arm was ocular icterus not surprisingly and this did not lead to a significant number of treatment discontinuation xin all of these arms treatment discs
Continuations were low there about 5% in all arms most of these were grade 1 adverse events the other adverse event data that i thought was worth mentioning was the lipid data in study 102 the study that compared stri buhl to a triplet total cholesterol ldl and hdl changes were all worse in the fabri nor a triplet arm so strive bill does seem to have benefit in
Compared a triplet in terms of lipid data in study 103 comparing stride bill to truvada boosted as a new birth there really was not much difference triglyceride changes were slightly worse in the boosted a design of your arm but really was not much different and then that brings me to the renal changes which are worth talking about so in study 102 there were with
A small percentage 1.4 percent treatments discontinuation xin this dry build arm and what was seen was an increase in the sperm kratt need of about oh point one to point to with a median of 0.14 by week 48 this correspond to an estimated gfr decrease of fourteen point three in the l by tobeco basis that arm versus three point zero in the fabrice arm and this was
Statistically significant but when broken down to those patients who had proven to not alert toxicity the serum cracking increase was at least point four in all of those patients and so the notable things here are that when kobus estat is used the increase is generally around 0.12 point – it happens rapidly and then stabilizes and those patients who have proven to
Not their toxic toxicity seem to have an increase of at least point four graphically and i know this is a bit small but this is the change from study 102 i know this still says quad should say stri build but you can see here’s the pointer you can see a rapid increase of about 0.1 then over 48 weeks it really stabilizes and doesn’t rise much after that and then this
Is the fabri –nz arm down here which didn’t change very much and why this happens is it kobus is that like rope it of rain and like dolly tag of ear blocks the proximal tibial secretion of creatinine so this will make estimated gfr when estimated by the cockroft gault or other equations this will make estimated cratan clearance appear to change studies that have
Looked at actual cracking clearance using using measures like io hex all have shown that actual cracking clearance does not change so this is an issue with several new or recent medications like cove assist atropine and die or tiger beer so this is going to be an issue that we’ll need close monitoring once we start broadly using cove assist at containing regimens
Briefly i just want to mention the resistance data from study 102 and 103 because i think it’s instructive looking at the columns here in green this is from study 102 the thing worth noting here is that in both arms about five percent of patients had bare logic failure that was analyzed for resistance about two percent actually had resistance in the elbow tag revere
Cope assist at arm most of those had did develop integrated resistance the most common mutation was the e92 q or an rti resistance the most common being the m1 a for v and not surprisingly in the fabrics are most patients developed ak-103 n but it was a very different finding in study 103 we’re in the boosted p i arm no patient who developed very logic failure
Developed resistance so as we’ve mentioned here in these sessions before boosted p eyes have much more a much more robust barrier to resistance than a fabrice or than stri build so this although stri build is new and has this new integrase inhibitor this is not a regimen to consider in patients whom you are nervous about their adherence in anyway these do not have the
Robust adherent robust resistance barrier that boosted pis do so just summarizing the key points here what we’ve shown in these two studies struggled is non inferior to the two first-line regimens a triple a– and truvada with booster des and revere it has fewer cns and lipid side effects than ana fabrics containing regimen but similar gi side effects to ritonavir
Boosted atazanavir because of the cove assist that component a point 1 to point 2 milligrams per deciliter increase in serum creatinine may be seen and may be expected but an increase that’s greater than this should trigger a workup fortunado toxicity what what’s in the package insert is to avoid initiating stri build if the cracking clearance is already less than
70 and to stop the medication if the cratan clearance drops to less than 50 so let’s keep going to remember the other key points remember to counselor patients to take it with food at least two hours apart from an tasks and remember that it has a low resistance barrier and i’ll just finish am i mentioning a couple other things on the horizon that you may start to
See elbaite egg revere new drug approval application has also been submitted coab assists at new drug approval application has also been submitted independent of the co formulated stri build doll you tagged revere which is the other new integrase inhibitor which does have a much higher barrier to resistance because in phase three and we’ll start hearing more about
That and then the drug company that develops dri billet is also doing three separate switch studies a pi switch destroy build and n an rti switch destroy build and a rotary switch to strive build all of which i think will be very interesting and useful they’re also doing studies of stri build in patients with pre-existing renal insufficiency and a study of stri build
In women so we can get better data in that category and then the other new drug that i think we’ll start seeing more data on is what’s being called the seventy three forty quad which is the quad but instead of tanaka veer has a tanaka vert pro drug in it which hopefully will have less renal side effects so these are things that i think we can look out for hopefully in the near future
Transcribed from video
Stribild (The Quad Pill) By MWAETC Project ECHO