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I will get back later on in the day with a more detailed analysis, but I just wanted to say that this is just the beginning here. Those who think that this SP is what it is don't know the value of what they have in their hands
Congrats all
I was not surprised by the CR rate as I predicted between 40 and 42 % in previous posts, but I am happily impressed with the safety results.
To all fellow shareholders, enjoy your gains , this present could not have come in a better time
This is great news and it is another reason why I was urging long term holders to look beyond P3 results so they can cash in the long term benefits of VCS, one of them being the absence of any adverse clinical impact on glucose parameters ( contrary to Tacrolimus).
As mentioned in the PR, this study ( benefit ) will be added to the NDA filing in mid 2020.
Also on a side note Watson, even AURORA 2 will take a couple of years to finish, we are expected to have results on early patient enrolments ( we are expecting something between 50 to 80 patients to have completed AURORA 2 by the time they announce P3 results ), and even though it is NOT a requirement for the FDA approval next year, the FDA has requested Safety data from AURORA 2 ( you can see how much FDA is focused on Safety after the 11% death rate that hopefully will be cleared out with P3)
Watson, it is a blinded trial. Those who are kn MMF remains on MMF and those on VCS remains on it. This will remain blinded until the release of the AURORA 1 trial
Gonna be a great thanksgiving weekend. the recent climb in SP is a nice indicator of what's coming. Good Luck to all and enjoy the holiday
from 9 August 2018 NR : " We are excited to announce that the AURORA Phase III trial in lupus nephritis is running ahead of schedule and we now anticipate completing enrollment in early Q4 2018. We are extremely pleased with the trial’s progress thus far and having patients roll over into the AURORA 2 extension study reinforces our confidence in the program"
from 8 Nov 2018 NR : "A significant percentage of patients who have completed the AURORA trial are rolling over into the AURORA 2 blinded extension study (“AURORA 2”) from the AURORA Phase III clinical trial. The purpose of AURORA 2 is to assess the long-term benefit/risk of voclosporin in patients with LN; however, this study is not a requirement for potential regulatory approval for voclosporin"
Awlau,
there was a question from an analyst about the numbers recruited in AURORA2 but CEO didn't provide a number because it was never announced in a public NR, so no , but if you read their NR (especially those before the announcement of the last patient recruit in Sep 2018 , the previous CEO mentions that they have a significant % of the patients who finished AURORA rolling in to AURORA2 and this in his opinion was a great indicator. (I will try to find that NR again and post the CEO words here)
I highly doubt there is a leak Watson. it is always possible but I highly doubt it in AUPH based on their historical patterns. when AURA results was announced in march 2017 the only pre-results move was on the same day that the results were issued and it showed an increase in volume and a slightly increase in SP, and that is why I thought that we will see results yesterday but since we had none I am considering that this is short covering or some reaction to some rumors about new senior staff. Short covering is great because it also confirms to you that there is no BAD leak either.
This is the perfect time to add, this trial imo will have a p<0.05 , no doubt in my mind there, I am just crossing my fingers that we get a good safety result going with it, because no one can control safety with this disease, but management didn't seem to be too much worried in the last CC regarding safety which makes me like my chances more.
for those planning on selling at the first chance after results announcement ( if success is announced), remember that if you wait a bit longer for some long term results coming from AURORA 2 your profit would be multiple when nephrotoxicity results start coming in proving that this drug is really something else. so far, there is no indication that this drug is toxic for the long term . but again, to each his own situation, but I really urge holders here, especially long term holders to see beyond the results of this P3
ZZaatt, Hispanic in this context is mostly the population from the American Continent. all previous trials have dealt with that the same way. in AURORA, you can see an increase in sites from Latin America and the US
March 1st 2017, over 4 M shares traded, SP went up and a NR was released in the evening after market close confirming AURA achieved primary endpoint at 48 weeks.
I have a feeling that history will repeat itself TODAY with results after market close
Merc, the average target price set by analysts is 16 $ if they achieve primary endpoint. if they prove that long term nephrotoxicity is low , target price jumps to $ 40
same pattern happened before issuing AURA results in March. looks like we are heading for a good trial results
Luna, when I mentioned that 2 patients relapsed in AURION, I meant it that we had 7 patients with a CR at 24 weeks and we lost 2 at 48 weeks for a total of 5 patients, I didn't mean that their LN worsened. Actually if you read the presentation that Dr. Huizinga presented in Australia in 2017, he gave the reason for the drop. it was because of AE ( 1 patient had a community pneumonia, 1 patient had a severe fever with unknown cause). and a 3rd one dropped because his SLE worsened. so AE caused 2 patients out of 7 with CR at 24 weeks to drop ( that is a lot). in AURA, we were lucky that all patients with CR at 24 remained in the study at 48 weeks but this is not guaranteed ( and the AURION is the perfect example).
This goes back to what I was saying that AURA was our best result: the Asian Indian population that gave us 59% CR is no longer there, the White population % that gave us 61% CR will be lower in AURORA. Based on some scenarios I have prepared, I am seeing a VCS CR % between 40 and 42, assuming we can take down the death rate from 11% to 2% and depending how the Hispanic population reacts to VCS.
In my opinion, this is more than enough to beat placebo with a meaningful statistical Delta but I am not seeing us hitting 49% like AURA. I am sorry some don't like what I am writing here but that's my 2 cents.
Roche is not the SoC right now, and the main advantage of VCS over Roche is that VCS has much a rapid response than Roche. this is more important than a CR at 78 weeks. for comparison we had a much higher delta vs placebo at 24 weeks than Roche. see attached details of Roche study. start page 18
https://www.roche.com/dam/jcr:656bf1a5-768c-4d91-a3db-b7440c3d6e7a/en/irp20191112.pdf
also we still don't have VCS long term results so we can still beat Roche numbers at 78 weeks. but the main thing is the rapidity of the response, and this is what made Neil comment that both drugs can be complementary and not competitve
I will try to clarify my thoughts once and for all because I can see a lot of confusion here:
Nothing changed in my Bullish thoughts regarding AUPH since the first day I started posting here. I still believe P3 will be successful, but imo this means achieving a P<0.05 , NOT beating AURA numbers.
lets keep our focus on the prize. Management mentioned in their CC , we need 2 consecutive P values <0.05, That's all, we are not in a pissing contest with AURA here. Both AURA and AURORA data will be used for FDA approval. by increasing the % of Hispanic and Black in P3 we are covering a full global population in 2 trials and addressing a major need of the US market (since they form most of the patients in US). Lets not overthink it, P3 will be successful as long as our safety is good. for all those who think we are doomed if we don't hit AURA's numbers, I think you are making a big mistake in your evaluation of TRIAL SUCCESS.
Agree Awlau, I just posted about that
Mkc, I think the CR rate will lower in P3 than P2, but this doesn't mean it is a failure. Again, please go back to the company's latest CC where Neil mentions that achieving 2 consecutive p value <0.05 is what the FDA wants and that this has never happened before, also that a delta of 10% if clinically significant. those are not my words, this what the company is aiming for, of course the higher the delta the better, but what they want now is to get the drug approved by FDA, which imp will happen because even with the increase of numbers of Blacks and Hispanic , delta over 10% is achievable . ( remember that placebo achieved ZERO CR with the Black community in Placebo AURA (there was 6 Blacks in the placebo), which means the increase will affect the placebo CR rate too, that is why I believe they will get a P<0.05, but to beat AURA numbers I highly doubt that
yes, this is P2 data, it shows that Hispanic and Black were a small % of the trial. in P3 you have 55% of the sites in US (Black, White, Hispanic), South America (Hispanic), Spain (Hispanic), South Africa (Black); this is a clear indication that the Black and Hispanic races will form a major part of the P3 trial; I said I am expecting around 50% because this is aligned with previous global trials done by others
link for Clinical trials for Aurinia
https://clinicaltrials.gov/ct2/results?cond=&term=aurinia&cntry=&state=&city=&dist=
you can read the sites selection for AURA and AURORA, it gives an idea about the Race in each trial
here is the link again, it is table 1
As for the 50% I mentioned in P3, this is aligned with global studies done previously (ALMS, Abatacept, to name few).
also check on clinical trial site, you can see the countries for P2 and those for P3, and you can clearly see the number of Hispanic and US sites go drastically up which means they are more focused on Black and Hispanic in P3.
a small adjustment to my statement earlier, I said 7 Hispanic were in P2, actually there were 9 in low dose VCS in P2, sorry for that I was writing from memory
it is in the table in the link I sent in my post earlier
Jess, I am not trying to go around your questions, it is just I don't check this site every minute.
I don't know exactly what you are looking for so I will answer the best I can
1) the 31 country sites come from clinical trial site
2) the fact that they used 27 country is coming from the NR of the company itself
3) the Quality remarks and finishing ahead of schedule is something I read and was said by an analyst that follows the company, also finishing ahead of schedule was something the company mentioned in their NR, but the comment that this means they got quality patients came from the analyst
if you have more questions please ask, but lets keep this calm and informative
Jess, you can read this link, it can tell you all what you need to know on the details of P2.
https://www.researchgate.net/publication/328830731_A_randomized_controlled_double-blind_study_comparing_the_efficacy_and_safety_of_dose-ranging_voclosporin_with_placebo_in_achieving_remission_in_patients_with_active_lupus_nephritis
just to be clear, again, I am not saying that they will fail P3. if the delta of 10% as mentioned in the CC is enough to get a p<0.05 then it is still doable. All I was saying through my posts yesterday that I don't think they can beat P2 numbers , that is all. Few things to consider in this P3 that are different than P2:
1) the race mix is different, no Asian Indian and less White and increase in Hispanic and Black
2) more patients with a longer history of LN but management said it is less than 10% and won't impact the results
3) the change in race could impact the % of patients achieving a CR after 24 weeks. in P2, 100% remained in CR after 24 weeks but this can change now with a different pool of patients ( remember that AURION had 2 patients out of 7 relapse between 24 and 48 weeks , and they were Asian)
my final take on this is that P2 were the best results we could have. P3 will have lower % but I still believe strongly that it will be enough to give us a p<0.05, and this is all we need to get a potential approval from the FDA.
Also, we should never forget the safety issue. this is a wild card and there is no concrete de risk, even though I am more comfortable with the measures they took in this phase
Jess, because those percentage used in P2 are not enough to prove that the drug works on them. 3 Blacks and 7 Hispanics treated out of 89 with VCS in P2, that is not even close to get FDA approval for the US population where most of the patients are not White. They had some early numbers but they need to show it on a larger population. I am expecting that Hyspanic and Blacks will form around 50% of the total patients. This is aligned with other global studies and is a logical outcome of the increase of the study sites in the US and South America
Ok, just so that no one misunderstands me here, I am still bullish on P3 and still believe that they will meet their primary endpoint, i am just not convinced that they will beat P2 numbers for the reasons I mentioned in my previous 2 posts. The claim by management in their CC that delta of over 10% is clinically statistical is the main reason I am bullish. I repeat, we dont need to beat P2 numbers , we just need to meet primary endpoint and according to management we just need a bit over 10% to do it
Jes, they need to treat all races otherwise it is not global especially that Black and Hyspanic are the bulk of the US market
Even though I am bullish on the outcome but I would forget this 50% CR. Even though it looks like the P2 and P3 are the same, the choice of population is extremely different, most of the P3 will be Black and Hispanic, something VCS tested shallowly in P2 (9 Hispanic and 3 Black), we are not sure we will have a meaningful difference with those 2 races knowing they are the hardest to treat and using low steroid. I think we would be lucky if we got something around 40%. Management talked about delta of 10% is clinically meaningful, so I hope they will achieve it, i think they will but P3 is gonna be less impressive than P2 imo, and the safety is always the wild card, we dont know if we will be lucky there but sure good yo know management made safety adjustments after P2
This could be any day now. from the dates mentioned on the site looks like the last patient (Sep 24) decided to enroll in the AURORA 2 otherwise the last visit would have been Oct 22 (after 4 weeks) instead of October 10 (must be for a different patient). the CEO has always mentioned in their PR that a substantial % of patients who completed the study are enrolling in AURORA 2.
we had over 9 M short end of October, and last Friday the daily short ration was 10% of the total daily traded shares( it is normally between 20-25%), I think the shorts have started to cover on Friday after the management CC
BR, delta of 20% gives us way better than p<0.05,
As an example to that, in AURA the delta achieved by the high dose was 16% and gave us a p<0.02, and this was with a lower number of patients( around 89 in each arm). In AURORA we have double the number of patients so this empower more the results. Over 10% as mentioned by Neil is enough to give us a p<0.05
Heldnova,
I agree that it doesn't impact the outcome:
1) this is split between both arms so actually it is les than 5% in each arm
2) this is more impacting the placebo arm and can work in our favor since those are normally non responsive to the existing SoC which in our case is the placebo +MMF
3) even though they are historically non responders to SoC, they could respond to VCS which is a new treatment and this is an opportunity to test it on them
4) Normally it is risky to have this type of patients in your trial since you don't know how they will respond, but I would be worried if the % was much higher (like the Abatacept trial where they consisted of more than 35% of the trial patients)
Maciste,
he was talking about the difference between P2 and P3 in the inclusion criteria. in P2, a 6 month biopsy was required when in P3 they increased the interval to 24 months which allows the treatment of some patients that have a longer LN history (which is not good normally because those are normally non responsive to treatment, and I was a bit worried actually about this change between P2 and P3), but what Neil said is they did it to allow for a small number to participate in the study (around 10%) and it doesn't have an impact on the study results (since the 10% will be split between both arms and impacts both of them. This change got me concerned that the % would be much bigger than 10% but Neil's answer clarified things). I think this is a requirement of the FDA same as they needed to have a certain % of Class V in the trial.
Overall, I was extremely satisfied with the CC and Neil's answers, it cleared a lot of my concerns regarding some of the points that were kept a bit foggy.
That's right, in AURA we were able to achieve p<0.001 that is why I am saying p<0.05 should be a walk in the park but it wasn't until yesterday that I knew that this was the FDA requirement; we don't have to beat AURA's numbers we don't even have to compare to them, all we need is this p<0.05.
This leaves Safety, but from the CC yesterday they didn't have to worry much about it this time, I heard Neil say that they took some Safety measures with the study sites and one analyst mentioned in his question that the sites in AURORA were better selected than AURA's
All we need is this p<0.05 value at 52 weeks. from my understanding of the CC yesterday is that FDA told them to get p<0.05 in 2 consecutive trials ( something that has not been done yet in LN) and they will be approved (of course with a good Safety results).
This is something new to me and very positive. Management thinks that Delta >10% will provide this 0.05 threshold. Things are getting more bullish by the day
of course, this is a very bullish signal since it shows you the AURORA trial will be a success because you will be comparing to a Placebo CR of around 20%, also it shows you that you are better than the competition ( CR of 38% vs 49% with faster CR with VCS). the only difference is that Roche got the Break through status from FDA and we didn't because of the Safety issues we had in AURA ( this should be solved in AURORA), and the major difference is that ROCHE study is for WHITE and HISPANIC while AURORA is Global ( they don't have Black or Chinese)
Now for those asking what is the comparison between the CR of VCS and the CR of Obinutuzumab of Roche, and accounting for the NO RESCUE THERAPY requirement , we have the following :
Roche CR :
CR = 35% (including the Sediment criteria)
CR = 43% excluding the Sediment criteria(aligned with AURORA criterias)
CR = 38% Accounting for the no rescue requirement (aligned with the AURORA study protocol)
So to make a fair comparison, you should compare to a CR of 38% at 52 weeks, and this doesn't account for the fact that we are using half the amount of steroid
Here is the details of the Roche study
https://www.roche.com/dam/jcr:656bf1a5-768c-4d91-a3db-b7440c3d6e7a/en/irp20191112.pdf
now this is how it compares to VCS (on the Placebo side):
1) Steroid use : median Roche is 11 mg/ day vs VCS: 5.4 mg /day
2) UPCR : mean Roche : 2.9 vs VCS : 4.4
3) MMF use same amount for both studies 2 mg/day
4) Alternative CR at 52 weeks without the sediment criteria Roche: 28% (Placebo)
5) Most patients in Roche are Hispanic which is aligned with VCS AURORA trial
Discussion:
SO basically if we use the same CR criteria of Roche, our CR for the placebo should be around 28%. but VCS has some requirements that Roche DO NOT have:
1) No Rescue therapy allowed. this shed 9% automatically from Roche CR since they had 19% that required Rescue therapy (10% of them discontinued)
2) No high dose Prednisone allowed in the last9 weeks of the study (week 44 thru 52) AND our steroid taper is more aggressive (our median was 5.4 mg/day vs 11 for Roche . so this criteria should reduce the CR % further
Conclusion:
1)The Roche study Placebo CR should read MAXIMUM 19% if they apply the VCS CR requirements
2) the Death was 7% in the Roche study Placebo study, where patients were mostly taken from Latin America and the States. I know this doesn't imply we will have the same % in AURORA but it is something possible , and if we have the same rate it will help with the safety issue we had in AURA.
This gives me more confidence that we will achieve the Primary endpoint in AURORA .
In the AURA trial, The Mean duration of CR for VCS was 17.5 weeks vs 9.4 weeks for Placebo, which means we have twice the CR duration than SoC . The change in the low prednisone condition (<10 mg / day to achieve CR) from week 16 thru 24 ( in AURA) to 44 thru 52 (in AURORA) will have a significant impact on the Placebo arm since they won't be able to increase the dose in the last 9 weeks of the trial if a patient relapsed ( 9 weeks is also the same number of weeks that a placebo CR lasts). it could reduce the placebo CR % significantly while not impacting the VCS arm who has a double duration for its CR.
This Hedge funds action is no indicator at all. those 2 funds dumped $ 2.2 M worth of stock , which is 2.4% of the $ 94 M still held by the other 11 HF. $ 94 M worth of stock represent 20% of the share structure, this is a big sign of confidence from the HF in AUPH. Day to day action means nothing when the fundamentals of the company keeps getting stronger with each NR