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Enhver påvist effekt i kreft spredning og med telomerase som target vil utløse «interesse» fra BP. Kan ikke se for meg et scenario der HR er lik eller bedre enn 0.8 (fase 3 terskelen) hvor UV1 ikke blir tatt videre.
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Ikke for å mene noe annet enn at Ossato er den mest valide sammenligningen, men ble bare også litt nysgjerrig på hvor strekene lå pr. idag for CM067 og CM511 og med frihåndstegning ble det slik :
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@ketilaaj eller andre har gjerne forklart tidligere hva Ossato-kurven representerer. Jeg måtte imidlertid slå opp og fant denne:
Hvor i artikkelen kommer det frem?
Fikk du opplyst dette direkte fra selskapet eller har noen andre fått dette direkte fra selskapet?
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Mot slutten av denne artikkelen fra 2021
Det statistiske designet for INITIUM ble forklart på Cowen-konferansen. Jeg stilte noen spørsmål rundt dette til CMO gjennom IR i etterkant, og fikk opplyst om dette. Tallet 0.73 følger automatisk av designet. Dette var altså ikke ny informasjon for en som forstår design av studier og statistikk fullt ut (noe jeg altså tydeligvis ikke gjorde). Det er jeg som har ropt først og høyest både her og på Twitter om at oppnådd primærendepunkt er HR=0.60, så jeg synes det er fint at jeg fikk en tilbakemelding som fortalte meg at det var feil.
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(post deleted by author)
Er det at “Tallet 0.73 følger automatisk av designet” bra eller dårlig? Gjerne også relativt til diskusjonen her inne så langt.
Nå bør fokuset være på hvor utrolig heldige vi som ikke har den kunnskapen og kjennskapen som enkelte her inne har.
Vi får analyser og vurderinger av noen meget kunnskapsrike mennesker med gode kontakter som gir oss uinnvidde en høyst uvanlig innsikt i en sektor hvor kunnskapen er i stadig endring og vanlige finansielle analytikere er sjanseløse på å tilby det vi får her.
Dette gjør de rett og slett av oppriktig interesse for vitenskapen og hva den kan gjøre for potensielle pasienter. Dette har jeg overhodet ingen tvil om!
De ser selvfølgelig også muligheten for å gjøre en for mange livsendrende investering hvis U lykkes. Dette er de så generøse at de deler med DEG!
Det som opprører meg er hvordan enkelte her nærmest angriper disse ressursene når det oppstår ting de overhodet ikke har noe ansvar for og ihvertfall ikke ovenfor noen her på forumet.
Til alle dere som bidrar mer enn noen kan forvente når det gjelder en slik case og ikke minst at dere deler så fritt og åpent som dere gjør , TAKK!
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Det er bra at studien er designet for en HR på 0.73 og ikke 0.6. At primærendepunktet nås ved en høyere HR enn vi tidligere regnet med øker dermed sannsynligheten for at Ultimovacs kan si at primærendepunktet er nådd
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Her er transcript fra Ultimovacs sin presentasjon @Cowen.
Har retten noen feil men prøvd og ikke endre semantikken noe så transcripten er så autentisk som mulig. Var noe dårlig lyd på slutten men tror alt kom med korrekt.
Merk at starten er noen sekunder ut i presentasjonen.
Carlos
Phase two studies, all of these studies are randomized comparative, but we also have long term phase one data showing a very good safety profile and also long duration of immune response. After seven years, eight years post vaccination, we still find T cells circulating that are educated to recognize cells expressing telomerase. And as you will see we are in a very exciting period for the company as we out of these. Five phase two studies that we are running, two of them are going to read now during the first half of 2023. We submitted the phase one data to the FDA and we received fast track designation for combination with both ipilimumab and pembrolizumab and also offer orphan drug designation. We also received a lot of interest from specialized oncology groups and the pharma companies. So we have a lot of collaborations in this very broad development program. A little bit on the financials, the company was founded in 2011. And we did an IPO in Euronext Oslo Stock Exchange in 2019. After that we did the two direct placements and so we have it now at the end of the Q4 2022 about $42 million in cash what gives us an expected runway to meet 2024. So very good place to be in these very volatile times. Our market cap is as you can imagine varies, but is approximately $400 million and. we are small company with 26 people located primarily in Oslo, Norway, but also in Uppsala, a city north of Stockholm. In Sweden. Our main shareholders are very big family offices, but also some institutions like the Norwegian Pension Fund and these are all very long term investors. About 70% of the company are in the hands of the the top 20 investors, so with a very long term perspective. But of course allows the company to focus on the business. And with this, I give the word to Jens that will talk you through the science, but also the clinical results and the clinical development program and then I will pick it up after that.
Jens
Thank you, Carlos so. So this slide is presenting the current clinical program in Ultimovacs and that pre top line represents our lead indication malignant Melanoma. We have conducted 2 phase one trial where we have results and we also have a third trial which is a randomized phase two trial fully enrolled which we expect readout from the first half of this year. Over the last years, it has been a lot of attention from other academic groups and also other pharma companies. So we participate in four other randomized phase two trials, one in mesothelioma patients, one in head and neck, one in ovarian cancer and one in non small cell lung cancer. Out of these four trials the mesothelioma trial is also expected to have a readout of the results first half of this year. Moving on to our hypothesis around how the vaccine is working. So as you know over the last decade checkpoint inhibitors have shown that if they unleash checkpoints and between the immune system and the cancer cells in some patients, you can see very good responses. This is due to the pre-existing T cell in T cells in that patient that can kill off the cancer, but in most patients. you do not see a sufficient efficacy from the pre-existing activating T cells in the patients. So other strategies is also needed to help these patients come into a complete response. We are developing a cancer vaccine that targets some antigen called telomerase. So a short background, so normal tissue to become tumor tissue different hallmarks need to be in place. For example, the cancer cells need to have a strategy for eternal cell division and then 85 to 90% of cancers the tumor cells have turned on and enzyme called telomerase to be in search of position. This is something that happend early in the development of the tumor and it’s also something that followed the tumors throughout the course of the cancer. So you can find this from early stages and in the primary and in the metastasis of the tumor. We have tried to illustrate the telomerase as an antigen in this street to the right, so we call this a truncal event. And the red color represent the expression of telomerase, and you can see over time that the telema race is also going out in their branches of the tree. This might be in contrast to some new antigens, which you can find in branches of the tree, but will not represent the full tumor, because it’s very important to emphasize that telomerase is an essential for that tumor cells. They cannot stop expressing it. If they do so, they will not be able to divide forever anymore. The vaccine itself consists of three long peptides. We are focusing on CD4 expansion with this vaccine. The three peptides cover a sequence from the catalytic site of telomerase and they are by intention placed there. So it will be difficult for the tumor to mutate itself away from recognition from the immune system. Also further in the three peptides there are several epitopes that can be bound to different HLA molecules high frequency agile molecules? So we do not do any HLA screening of patients prior to inclusion in studies. In our first phase one trials, we saw that between 80 and 90% of patients and have an immune response with this strategy, the vaccine itself and we vaccinate in intradermally on the belly, it’s 8 vaccinations in total, 4 vaccinations the 1st 10 days and thereafter we combine. And vaccinated with the same frequency as the drug. So they are combining with and we are always combining with checkpoint inhibitors. They believe there is this mutual interaction between checkpoint inhibitors on one side and the immune system on the other side. And after the expanded T cells are part of the immune system. We do combine with what is standard care in different indications or close to be so. Some words about the phase one trials in our lead indication malignant Melanoma. So we have conducted 2 phase one trials, one where we combined you have one with equilibrium in stage four patients malignant Melanoma and one where we combined with pembrolizumab in the in advanced malignant Melanoma or metastatic malignant Melanoma. For both these trials we did see a good safety profile and by that then we are meaning that what we see is the safety profile of the checkpoint inhibitors we are combining with except for injection site reactions. Also for the first trial with which I had 12 patients, we did see in response rates in one. Third of the patients, one complete response and three partial responders. Over the next few slides I will go to the efficacy signals from the UV1 Pembro trial. Most of these trials have been presented and published different places. And for the UV1 Pembro trial, it was presented at that school 2021 and also it was part of the plenary session at the SMR Conference in Edinburgh prior to Christmas. We have sent off the data from these two trials to the FDA. And received back fast track designation for both combinations and also orphan drug status for the vaccine in malignant Melanoma. For the 30 patients, I mean the UV Pembroke trial, you can hear see the development of their cancer. This is the spider plot of the 30 patients. Each line represents the patient and each box represent an image. 57% of the patients had a partial or complete response in this trial and we have also followed this patient for two years and we see after one year that 94% of the patients remain in response at that point. Here in this waterfall plot, you can see each column represents the patient and you can see the stage of the disease at the top of the columns or below. And also we have some information about different biomarkers. I will come back to that. But first of all as I said, we saw complete response in 1/3 of the patients, 10 out of 30 patients and a partial response in seven of 30 patients for your information beyond and below the waterfall you can see the numbers from the keynote 06 trial, which was the registration study for pembrolizumab alone. As you might know in this large studies for the CPI for example the keynote 006 trial in retrospect it was analysis done of different biomarkers like PDL one expression, tumor mutation burden and others. And they also found that if you had a PDL one negative trial patient, it is less likely to respond to the checkpoint inhibitors as compared if you have high PDL one expression. We also did this. Analysis in our study. As you can see in the table to the right and we actually saw the same response rate in those patients and with the PDL1 negative status as in the whole study as such, both when it comes to response rate, but also for the complete responders. And this was also true for the other biomarkers we analyzed tumor, mutation burden, interferon, gamma signal or signature and T cell infiltration. On this slide you can see a overview of the five phase two trials we are participating in. So they want to the left, they need some trial is our sponsor trial. The four other trials are studies where we participate except for the study in middle the focus trial, all of these trials are endpoint driven. So there’s the predefined number of endpoints we are waiting for in this trial to occur and when that happens the database is closed and we will thereafter follow the patients for overall survival over the years after. In the Initium trial Ipi+Nivo is the CPI and the plus minus the vaccine on top. As I said, this trial is fully enrolled and we expect readout first half of this year and primary endpoint is hazard ratio PFS. For the mesothelioma trial , it’s also Ipi+Nivo which is the CPI plus minus the vaccine. Also this trial fully enrolled and expect readout first half of this year the focus trial in middle and head and neck cancer. This is the Pembro indication. So it’s pembrolizumab plus minus the vaccine on top. If this is a landmark trial, so half a year after last patient has been included, there will be a readout of the primary endpoint which is also here PFS. The last two trials the DUVAC trial in women with the Ovarian cancer, BRCA negative ovarian cancer, the patients that are receiving either Pula Padim, Olaparib durvalumab or Olaparib durvalumab and the vaccine. In the last trial long back trial, we have the patients have PDL1 50% or above without the mutations and this is similar to the pembrolizumab indication or label. So in this trial we use Semi Plymouth and then price minus vaccine on top these two last trials that nubuck and landmark trial has quite recently started recruitment. So as you can see from the numbers at the bottom. Just a little bit more discussion about the these two trials. So the initial trial is our sponsored trial, it’s a trial that was including patients in the US and Europe fully enrolled as of June last year and we expect readout this year. First half of this year. PFS is the primary endpoint and the statistics is with the hazard ratio 0.6 and alpha 0.1, power of 80.
Jens
For the NIPU trial, the statistics is quite similar to the Initum trial, also here and we combined with Ipi+Nivo CPI plus minus the vaccine on top. We find it quite interesting that after we started this trial Ipi+Nivo became standard of care for this patient group both here in the US and also in Europe. So to finalize this clinical part of the presentation, I would say that that from the phase one trials I think we have had seen a very good safety profile that has not stopped us in developing the vaccine in different phase two trials. And also on the efficacy side where we think we have seen a good response rrates in different patient populations for example, both those with the low PDL1 and as compared to the whole group as such.
Carlos
Thank you Jens. So let’s talk a little bit about the, the potential for the use of UV-1 this looks like a, you know a busy slide but it’s it’s a good slide to show you. You know we, you see on the on the left a list of different cancer types and then you see the green boxes in the different indications where the checkpoint inhibitors are already approved as standard of care in the darker blue is types of tumors where we UV-1. Of being or was used. But here I want to emphasize the fact that you know when you look at the 10 or more indications in light blue, these are other indications where we could be running clinical trials. We already have five studies running, but you know with unlimited financial resources we could be running an additional 10 indications. And this of course this is just to show you that as long as the cancer is expressed telomerase what is a lot of them and there is a checkpoint inhabitor approved or in the final stages for approval. We can be used in those indications. So a lot of potential for growth of UV1 in additional indications. Also as you know very recently the checkpoint inhibitors are migrating more into the neoadjuvant and the adjuvant a part of the the treatment. So new adjuvant is an area also that as a vaccine would make absolute sense for UV1 to be part of the thermal mentor. So we we are looking into the this as another potential for growth. So all of this is really emphasize the the, the value for UV1 in a very broad usage and if you see that we are being combined with five out of the top 6 selling checkpoint inhibitors and you know then then really the size of the market for the checkpoint inhibitors you see that you know there’s a lot of potential for. UV1, so not only in terms of the indications and the broad usage but also as already Jens mentioned because we have some key competitive advantages versus other approaches in this space. So we are using to easy to use intradermal injections. We are a truly off the shelf product being kept as a dry powder in a normal fridge and then reconstituted with sterile water. We don’t need to do any pre screening of patients. We don’t need to do any biomarker analysis in order to enroll patients. So very easy to treat these patients you know and really allowing for easy access for patients even if they are not close to very specialized centers.We have a simple manufacturing process. We work with one of the leading peptide manufacturing in the world, polypeptides and very importantly you know we by the time we are ready to move to the next phase of development, we are going to have a commercial process. In place what is very important for partnering discussions but also for potential discussion with the authorities for accelerator conditional approval. If the data is very positive, it’s three we pass already 3 shelf life. So nothing really complicated when they think this is a very key advantage when the patient needs to be treated with UV1, but let’s talk about what what comes next. We as a company we are recognized by basically delivering. On what you promised to market, but we are really now at the time where it’s a very exciting for the company as Jens mentioned we have the two to trials, the Initium and the Nipu trial reading now the first half of this year. And this is due to the fact that despite these studies starting to enroll patients in the middle of the pandemic in June 2020, the team did a great job working with the investigators to enroll these studies fully during the pandemic in a very good Time. And if these studies are positive, of course you know this will trigger a series of initiatives that the company is already preparing for. One of them is discussed with the authorities in terms of what is going to be the next phase of development together with several advisory boards that we are planning. And if the data is very positive, as I mentioned to discuss with the authorities what would need to be required for us to get a accelerated or conditional approval. On the other hand, you know we as a company we’ve been in touch with the strategic partners as a company we are prepared to move to the next stage of development. We can do that at 1-2 indications. I think that is important that is secure. But we have been publicly in saying that to you know we have a strategic partnership with the big farma that allow to expand the clinical program and of course give access to a bigger number of patients who have access to everyone in multiple indications, so these. activities will of course accelerate on the back of positive data and also you know, we continue to introduce the company to more and more investors. You know, we are of course very well known in Scandinavia in the northern part of Europe, but we have been introduced in company, you know, across Europe, the US and other regions because I think that if the data is positive will be transformational not only for the company and for cancer patients but also for the space, you know. In a series of meetings you know we receive a lot of encouragement from farma and investors because as all of these studies are randomized and comparative. If these studies are positive we will be the first company with the universal vaccine and with comparative data that showed the concept that cancer vaccines work. And a lot of people are hoping that this is the case because there is a lot of value for for patients and of course we don’t have just these two studies then the. At the next study we’ll be reading in the first half of next year and then we’ll come the the Dovacc ovarian cancer and the lung back in in lung cancer. So as a company we have multiple events coming soon. So as as takeaways as a company we are developing universal cancer vaccines to really enhance the efficacy and durability of the other immunotherapies. We can be used across the board that in multiple cancer types and in combination with multiple immunotherapy combinations we have the key advantages namely that we are off the shelf and easy to use. We have shown a very good safety profile that as you know is very important particularly when you start treating patients with combination of two drugs, three drugs. showing a very good safety profile is very important in that space when when we treating with seriously adverse patients and we also shown that you know the immune response that. Induced as a long duration the broad development program really shows the strong potential for a very big commercial potential. And the five phase two, five phase two randomized trials that are ongoing also have the possibility to to show that we have received the external validation from the FDA by receiving the fast track designation and the orphan drug designation, but also from a key oncology groups and also from Big Pharma in the mesothelioma. The Bristol-Myers Squibb supplies the investigators with ipilimumab, nivolumab and in the ovarian cancer AstraZeneca supplies to road map and Olaparib. And of course this is also a validation very rewarding. We didn’t have much time to talk about the second platform that we have that that platform that is a very innovative vaccine adjuvant platform currently in phase one and with a lot of potential. We have an experienced team, a strong shareholder base that really supports the company and we had a good and expected runway to meet 2024 that really takes us across this multiple value inflection points. So I think that as a company we are in the really in the right direction and we all hope that on the back of positive data this will be transformational for cancer patients. And with this I want to thank you for your attention.
Carlos
Are there any questions?
From the audience.
Audience
We throw out a question.
Audience
You guys have two data read out the first half of this year. Can you maybe share some expectations from the competitive perspective like what should we look in that data, you know what would constitute a successful result in those two trials and also thoughts on, you know what would you need to show in order to potentially Make those pivotal studies.
Carlos
Jens. Do you want to take over? No. No, he is miked.
Jens
Yeah, yeah so. So the design of this study is the statistics in these studies, they are typical phase two statistics. So as a base case positive trials will in a way indicate that it’s covered to go into phase three development in the different indications, as I said, we have to have a hazard ratio of 0 .6 right now and that is a number that is discussed with Doctor Sarah in the US and Europe to agree on what will be a clinical relevant result in such a trial. So when this trial reads out positive with the current statistics and that is understood by the environment that this is clinically relevant for patients. That the communist situation where you start to discuss this as a pivotal trial, I guess you need a lower number and that and this is something that is discussed with the authorities and you are also advised to move forward with some kind of accelerated approval. But I guess you need the numbers below 0.5 if I personally should throw out that number.
Audience
So you haven’t discussed it with FDA.
Jens
So, so when we discuss or in general when you discuss these kind of studies with the the authorities you are proposing something and they are going to make you aware and that the statistics and the number you have is can lead you to this and this different scenarios and to be in a position for kind of conditional approval and we need to have a number that is beyond what we have as a base case in in our trials. So this is not directly phase three trials as such or pivotal trials…
Carlos
So just to to confirm, yes the the protocol for the Initium study was discussed with the FDA and the EMA because 50% of the patients in the study are recruited in the US so that the statistics for the Phase II study were discussing the grid by the FDA and the we know that moving to a phase three we will need of course to increase the the number of patients. And also move the primary endpoint from PFS as a ratio PFS to overall survival what is typical in phase three studies, but the the positive study will be the the next step will be moving to pivotal studies.
Audience
Great.
Carlos
I think with that we’re pretty mucho ut of time. So thank you very much. Thank you.
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Utifra hva Bjørkhem svarer her så blir jeg igjen forvirret ang. hvilken HR som kan anses som et bra resultat.
og er det også HR han snakker om her :
But I guess you need the numbers below 0.5 if I personally should throw out that number.
I slutten av forrige uke ble det klart at Ultimovacs selv har HR=0.73 som mål for studiet. Ved å bruke en forenklet Excel modell for estimering av HR tilsvarer dette ca 39 events i kontrollarmen både for INITUM og NIPU. I plottene under er dette nivået lagt inn som en blå linje. I tillegg er 6 uker dataanalyse markert med et grønt felt. Kurvene er nøyaktig like som før, det er kun informasjonen beskrevet over som er lagt til som grafiske elementer.
Betydningen av de fargede linjene:
Gul linje :
Det er like mange events i kontrollarmen og den eksperimentelle armen .
Dette betyr at UV1 ikke har effekt.
Blå linje :
Endpoint met.
UV1 har klinisk nytte.
Dette er et veldig bra resultat.
Grønn linje:
HR brukt i studiedesignet (og det mange tidligere trodde var studiemålet)
UV1 har veldig god effekt.
Dette er et veldig, veldig bra resultat.
NB 1 : Tallene i beskrivelsesboksene reflekterer avlesning på angitt dato, dvs tidsbruk på dataanalyse ikke er tatt hensyn til.
NB 2 : Analysene er basert på at historisk studier er representative for de studiene vi venter på resultater fra.
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Slik jeg forstår Jens angående HR below 0,5 så er det:
“That the communist situation where you start to discuss this as a pivotal trial, I guess you need a lower number and that and this is something that is discussed with the authorities and you are also advised to move forward with some kind of accelerated approval. But I guess you need the numbers below 0.5 if I personally should throw out that number.”
Han sier vel at om data fra denne studien skal holde som en pivotal studie der man kan få en accelerated approval så må HR være under 0,5.
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OK - så med en HR på under 0,50 så vil de kunne tenkes å få godkjent UV1 til salg/bruk i markedet på bakgrunn av INITIUM og/eller NIPU studiene og ikke måtte vente på gjennomført fase 3 ? (Men jeg antar fase 3 likevel må gjennomføres uansett hvor gode fase 2 resutatene er ?)
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Ja, ja fase 3 må uansett gjennomføres, men vi hadde vel sett for oss AA og midlertidig godkjenning ved HR=0.6 og ikke under 0,5 ?
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Nå er vel strategien å inngå en avtale med et BP på gode data, så AA og å gå til markedet med UV1 alene er ikke pri1 tror jeg.
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Supert oppdatert.
Jeg googlet litt på 1 og 2 sidig og signifikans osv. Synes kapitlet nederst i dette innlegget var litt artig. Ultimovacs har selvsagt sitt på det tørre iogmed at det står klart beskrevet at der er det ensidig som gjelder i NIPU.
Under the alternative hypothesis, the HR is assumed to be 0.60. To test the null hypothesis with 80% power and a 1-sided alpha level of 0.10, a total of 69 PFS events are required.
Det var en viss diskusjon om valg av ensidige versus tosidige tester i medisinsk statistikk rundt 1990-tallet (1, 2). Men en sak har alltid vært udiskutabel: Man må bestemme på forhånd om man skal bruke ensidig eller tosidig hypotesetest. Her har det antakelig vært syndet mye. Altman skrev i sin lærebok i 1991: «De få ensidige testene som jeg har sett rapportert i publiserte artikler har vanligvis gitt p-verdier mellom 0,025 og 0,05, slik at resultatet ville vært ikke-signifikant ved en tosidig test. Jeg tviler på at de fleste av disse var forhåndsplanlagt som ensidige tester» ((3), s. 171, egen oversettelse).
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HR=0.50 var det Bjørheim litt på sparket mente måtte til for å få overbevisende signifikans ved en tosidig alpha på 0.05. Men om man ser på @Boblegutten sine utregninger, så er p-verdien veldig lav veldig raskt under HR=0.60. Og det er signifikans og ikke HR i seg selv som er det viktige for å definere nivået som gjør at FDA evt. vil anbefale Ultimovacs om å søke AA.
Et poeng vi kanskje har glemt litt i denne forbindelse er at vel så viktig som effekt, så er safety et “hurdle” for å få denne anbefalingen. Med såpass få pasienter som 156, så skal de veldig overbevisende data på dette for å få det. Men nettopp derfor er det så veldig verdifullt at Ultimovacs har safety fra mange pasienter fra fase I, men ikke minst også at man leser av NIPU også sannsynligvis samtidig. Totalt blir dette en veldig solid datapakke.
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Svar fra Ulimovacs (Anne) på mine spørsmål vedrørende HR og AA i Initium/Nipu studiene:
"Hei!
Takk for tålmodigheten, beklager at dette tok litt tid.
Først og fremst: Det foreligger ikke noe ny informasjon eller endring i studiedesign i noen av studiene. 0.73 er ett (av flere) tall som har blitt nevnt ved flere anledninger. Jeg er ikke stødig nok i farmasøytisk statistikk til å uttale meg her, så jeg har for ordens skyld bedt vår statistiker forklare hvor det tallet kommer fra og hva det betyr (for oss ikke-statistikere):
«What is described below applies to all comparative randomized trials ever conducted anywhere that have powered/sized for some given hypothesis; it is not unique to your trial, or oncology or any specific disease area, it applies universally.
There is an important distinction between the assumed hypothesis we put forward when determining the size of a trial and the actual difference we eventually observe in that trial when it is completed. When a trial is sized, we set up the hypothesis that either there is no effect, i.e the true Hazard Ratio (HR) in the population of all possible patients is =1 (i.e. the null hypothesis) or that there is some effect, i.e the true HR in the population of all possible patients is <1, say = 0.60 (i.e. the alternative hypothesis). If we could do a trial involving all possible (=millions of) patients with the disease, we would know for sure which was true, the null or the alternative. But we can’t do that, we need to sample a manageable number of patients in trial and gather data to tell us which of these hypothesis is most likely the truth.
If we do a trial with N=120 and 70 events, 80% power and 1-sided alpha =0.10, then we might observe a HR = 0.52, which is clearly closer to 0.60 than to 1, so we say the data are consistent with the alternative (there is a difference between the 2 arms). But suppose we do the trial again, with N=120 and 70 events but now in different patients. Now we might observe a HR = 0.85 which is closer to 1 than 0.60, so we say these new data are consistent with the null (there is no difference between the arms).
It is also clear that if the observed HR in our trial is approx mid-way between 1 and 0.6 geometrically = (1x0.6)0.5 =0.775 ( which is ½ way on the log scale, ie. ln(1) = 0 and ln(.6) = -0.5108, so half way = (0-0.5108)/2 = -0.2554 and e-0.2554 = 0.775), then we are on the very tipping point of being able to say if the data support a true HR=1 or a true HR=0.6. In fact, using normal calculations and similar to any study, we can compute this tipping point, and it is an observed HR=0.736. This is precisely the HR that, if observed, will give p=0.10. You do not have to observe a HR=0.60 to reach p=0.10; in fact, if you did observe a HR=0.60 then the p-value would be <<0.10, it would be 0.0163.
The hazard ratio is a measure of the magnitude of the difference between the two curves in the Kaplan–Meier plot, while the p value measures the statistical significance of this difference.
In summary, with an assumed hypothesis of HR=0.60, 80% power and 1-sided alpha=0.10 and N=70, a standard calculation, tells us that with an HR=<0.736, we confirm that there is a difference between the groups in favor of the experimental arm. The p=0.10, tells us that the difference is significant. The lower the p-value, the higher is the significance (an HR=0.60 gives a p=0.0163).»
Oppsummert: Tallet 0.73 baserer seg på generell farmasøytisk statistikk, som er tilgjengelig for alle som ønsker å fordype seg i dette. Det er altså ikke «ny» informasjon relatert til INITIUM. Vi må nok vente på data før vi får svar på utfallet av studien.
Håper dette bidro til å besvare det første spørsmålet ditt. Til det andre spørsmålet ditt er jeg usikker på hva du konkret refererer til. Når det gjelder FDA og evt. mulighet for Accelerated Approval er det så mange faktorer som spiller inn, at dette spekulerer biotech-selskaper vanligvis ikke i. Standard-prosedyren er at når man har analysert data fra en studie ber man om et møte med regulatoriske myndigheter for å avklare og få anbefaling om veien videre. Innen det skjer vil jo topline readout fra studien være annonsert til markedet.
Til sist vil jeg bare si tusen takk for støtten, og at vi setter veldig stor pris på at du tar kontakt direkte med oss for avklaringer.
Mvh
Anne
Anne Worsøe
Head of IR & Communication
Ultimovacs ASA
M: +47 90686815
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