Yahoo is back. Now compare teh TWO trial designs by Ora for Allergans phs 3 and RGRX phase 2b3. RGRX had tougher patient inclusion that AGN. RGRX probably had far more "severe" dry eye puts. BUT! Look at ALL of RGRX primary and secondary endpoints. EVERY ONE OF THEM was designated an EFFICACY issue and NOT a safety issue! THEN? Look at what Ora gave Allergan's drug phase 3. Phase 3 trials are ALWAYS about final EFFICACY, not about safety, which is established in all earlier trials. HOWEVER! AGN had Ora design their phase 3 with 2 primary endpoints and 3 secondary. teh 2 primary are discomfort and staining. BUT! The AGN trial designates these PRIMARY endpoints as a SAFETY MEASURE, NOT efficacy! Same thing in secondary endpoint. One is a SAFETY measure! Then Ora put in secondary as EFFICACY measure "ocular dryness".!! There will NOT be ocular dryness if you put any drops in! Then they gave OSDI as efficacy measure. In sum, 3 out of 5 major endpoints for ALLERGAN, IN A PHASE 3 EFFICACY TRIAL......are NOT efficacy measure but SAFETY MEASURE! Which means? AHG trial will PASS all safery Phase 3 EASILY! It is a cake walk to WIN! But look at ALL RGRX primary and secondary. ALL EFFICACY measure with harder patients! Until JJ explains better, IMO?....RGRX got conned in their trial with harder patient measures and ALL efficacy primary.secondary. Ora gave Allergan a PASS onp hase 3 with almost ALL simple safety measures, which will pass easily. Rodman analyst will not see this. RGRX was held to a far greater burden, than what Ora designed for Allergan trial Read the designs CAREFULLYyourself!
Here was RGRX trial design to compare to AGN's:
Primary Outcome Measures:
Total corneal fluorescein staining score at day29 [ Time Frame: 29 days after first dosing ] [ Designated as safety issue: No ]
Total ocular discomfort score at day29 [ Time Frame: 29 days after first dosing ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
Tear film break-up time at day 8, 15, 29 [ Time Frame: 8, 15, 29 days after first dosing ] [ Designated as safety issue: No ]
Unanesthetized Schirmer's Test at day 8, 15, 29 [ Time Frame: 8, 15, 29 days after first dosing ] [ Designated as safety issue: No ]
Ocular Surface Disease Index (OSDI)© at day 8, 15, 29 [ Time Frame: 8, 15, 29 days after first dosing ] [ Designated as safety issue: No ]
HERE IS THE Allergan phase 3 dePrimary Outcome Measures:
Corneal Fluorescein Staining [ Time Frame: Day 57 ] [ Designated as safety issue: Yes ]
Ocular Discomfort [ Time Frame: Day 57 ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
Corneal Fluorescein Staining [ Time Frame: Day 15 ] [ Designated as safety issue: Yes ]
Ocular Surface Disease Index [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
Ocular Dryness [ Time Frame: 8 weeks ] [ Designated as safety issue: No
poster "investor" queried on AGN's new drug and he cut and pasted it's good results. Fine. They read great, but I dug more. He did not, and NOR did the Rodman analyst. It was a set up easier trial! BOTH done by ORA! I want go know WHY Ora does NOT used a standardized trial design for dry eye. WHY do some clients get and easy design, some get harder? If you DIG on teh AGN designs, they get WHY? It looks to me like RGRX got conned. Bad trial design, AGAIN. Dig! The AGN phs 3 has easier patient inclusion standards, TB 4 had tougher & harder patient inclusion. Here is how RGRX desired harder pts:N
"Have a Schirmer's Test score of ≤10mm and ≥1mm
Have a Tear Film Break-Up Time (TFBUT) ≤10 seconds
Have a corneal fluorescein staining score of ≥2 in at least one region of the cornea"
Now, I looked at the trial ORA designed for AGN, NONE of these are in the AGN design. Whoich means they have a lower thershold. AGN get's easier puts, RGRX get's harder patients. So who has a better chance? Clearly AGN. My next fact will show the actual phase 3 design for AGN, versus what higher bar Ora gave to RGRX!
Yes, I found that teh mimetogen trial is being done by Ora, and the also will be in the damn CAE torture chamber! here is teh trial identifier from clinical trials....NCT02665234.
Bo was right..there were issues in earlier mimetogen trials. Bush & Lomb decided they weren't worth it. So B&L terminatd teh agreement...Nov 2015 Allergan picked it up, after they got scared by Shire's LIFTEGRAST.
Bo also right that the one left in the cold is NOVARTIS/ALCON.
Also, no one has a drug for EYE NK...and we have a phase 3 going now, w/ Orphan Status. we also in tis trial had a GLAUCOMA PR not disclosed, yet.
Ah yes, that was it. Bausch & Lomb forst took this drug from Mimetogen. Then after a whikle they dumped it back on teh market. They did not want it. Then after LIFTEGRAST came around with a win, Allergan then picked it up in November. I do believe Ora did work on it early on. I checed teh clinical trials website, and I CANNOT TELL if Ora is doing the current trial...but I do see that teh primary and secondary's are almost exact same os ours was. They had no tertiary points, RGRX did. I woudl like to know if ORA is doing it. because if they are NOT, then Allergan got smart, becauae Ora threw us into the torture chamber CAE again, and we lost statistical that we HAD up to Day 27! I woudl like to know if mimetogen/allergan do it that way.....because it sure looks like it screwed up TB 4.
Bo might be up on it. But there was a history of mimetogen. I recall it getting bounced around. First they took the drug, then they dropped it, then they took it back? I'll have to check. Also, I recall earlier trials that flopped in it. not sure of this phse3 they say. but give a chore over weekend to look.
I am hoping that R&R can get an update on teh Eye NK. That is a sleeper. No one expcts it to pass. But only a few dozen patients and it has Orphan status, and it is a FULL PHASE 3 trial. EYE NK is not unlike severe dry eye. We passed severe dry eye very well. That CAE chamber did not help .....only ONE day they used it! for an hour or so. man. But we need that Eye NK signed up.. Finkel gives us nothing on it.
No fueler, it wasn't a home run. The first Restasis FULL phase 3 failed totally! Ours was a Phase 2b/3. With the data gotten from the FAILED phase 3, Allergan was able to design ANOTHER Phase 3 that won approval after. Restasis is now a $1.5 billion drug. Shire's dry eye drug LIFTEGRAST also basically failed it's first Phase 3. with that data they designed a second one, and met with success. NEITHER IF THESE DRUGS EVER HAD A "HOME RUN" in trials! This is what people don't get! Dry eye space is a minefield and teh FDA has finally realized that people need MORE drugs that Restatsis. The data is now in hand to design the phase 3 that will get us. They expect to start this Fall, Unless someone like Novartis makes a play for TB 4. They will see what the data has, and whether they think RGRX is priced right at a $60 million market cap for a $2.5 billion market they want in too.
Interesting point. Which means earliest R&R comment is Monday......but that also gives Rodman analyst all weekend to get his thoughts down nicely, not rushed.
I don't think this failed at all. We had issues....but the data they got where it did win can be used for a final one. Ora says they can replicate data. just need a non guess endpoint to match.
Ora uses the CAE because it does create over the top trial set up capability. No one else can do what Ora does, and the FDA seems impressed on having this CAE machine... is also a way Ora does pre trial work for companies. The FDA can't demand that all trials use CAE, because it is proprietary to Ora. But the CAE (torure chamber to us) chamber is not an FDA mandate for a dry eye trial. So the way RGRX stated it is this.......from Day 1 to Day 28...in severe dry eye population, TB 4 was at a 0.03 P value of reducing overall corneal staining. THAT IS A STATISTICAL WIN!. Then on Day 28 , the patients sits in the CAE chamber for about an hour or so.maybe bit more. They dose TB 4 as usual. THEN the next day, day 29........is the FINAL OUTCOME measure. but it appears that doing the CAE torture chamber day 28, negated much of the effects seen day 1-27. So next time DROP the CAE tiorture chamber! the FDA does not demand it! And average dry eye patients aren't looking to SIT IN A ADVERSE ENVIRONMENT CHAMBER during their flare ups anyways!
Just more BAd luck to RGRX. But I think now they have all they need for the final one. And the EYE NK may surprise too
It would not surprise me if someone knew something, somehow. At 1:00 pm to 4 pm, they sold about 300,000 shares.in a BIG rush.....from around 70 cents down to a low print of 45 cents, then we came back. I woudl cal it a "GMO" order......Get Me Out. But one poster here is in often contact with FINRA about shorting.....and because of that FINRA was watching RGRX trading. It woudl be very easy to trace back that account & seller. Whether it happens or not, who knows. The trial did not fail.. endpoint choices did...but it was not the clear win we all hoped for, either. So we go back and wait. And FINALLY, there is enough data for the exact phase 3 approval trial..from this one today
It's been just over four hours since the release. That shoudl be enough time for the Rodman analyst to write a research comment.....he has RGRX as a "buy" for his clients. he's a pro at this.....I'm just hoping that he sees some of the things I think I see in the trial results (or am I crazy)....it isn't "deep data mining"..it's pretty straightforward. if the severe dry eye patients were a separate endpoint, the trial was a big success...Also, it appears that if we did NOT use the torture chamber, Controlled Adverse Environment (CAE) for an hour or so on Day 28......we also would have had a good win in overall corneal staining........P 0.03
Will Finkel be able to spell this out to Rodman? When will he put out his note? I hope today.......and perhaps is he has good things to say (????) many scared sellers have sold. I bought a little.
This sounds nuts. It was a 29 day trial. We got the "total" (overall) corneal staining measure NAILED up to day 28. quote:
"RGN-259 had a statistically significant reduction in corneal fluorescein staining prior to entering the CAE on Day 28 when compared to placebo (p=0.034). "
But then on DAY 28*, they "entered the Controlled Adverse Environment Chamber..called CAE.so we are in that chamber ONE damned time during Day 28, and then on Day 29 measure you lost all the previous 28 days of a winning overall staining? Patients don't have to be in the CAE in daily life day 28, we have a BIG statistical win..a P value P 0.03. They sat in the horror dry chamber for an hour or so day 28.and it screwed up their eye all over again!. ANSSWER? if FDA does not require it, DON'T USE IT NEXT TIME AND WE HAVE A BIG TRIAL WIN!
It is still big. Shire estimates the world market is really $2.5 billion. And getting bigger as baby boomers age. It is only about $1.5 billion now because Allergan's Restasis owns the whole dry eye market..but the efficacy isn't so good in Restatis, and it has severe side effects. 35% - 40% of sufferers cannot use it. TB 4 can still be huge., even with moderate to severe popuation approval. TB 4 has NO side effects..NO safety issues... Upcoming approval Liftegrast showed it's Phase 3 that 53% of Liftegrast patients had side effects, but not badly serious. Liftegrast was also dosed for a FULL YEAR..365 days. TB 4 was dosed for a mere 29 days. PLENTY of room for TB 4!
Bo just posted that we flip flopped this time and got good result in teh INFERIOR region cornea, unlike last time. But bo writes that we had a miss in overal corneal staining. READ CAREFULLY what RGRX stated. It resads to me liek we GOT good statistical results in total corneal staining, BUT it got missed when they put patients in teh Controlled ADVERSE Environment chamber (CAE). SO? The FDA does NOT demand or require that trials have to use the CAE. Only Ora uses it. So if it is not required by the FDA...and it seemed to mess up this one...then next time, since it is not required, DON'T USE IT! read carefully what RGRX said:
""RGN-259 also improved a common objective endpoint – ocular surface staining after 28 days of dosing in patients with compromised tear film break-up time at baseline. In this population, patients receiving 0.1% RGN-259 had a statistically significant reduction in corneal fluorescein staining prior to entering the CAE on Day 28 when compared to placebo (p=0.034). "
SEE? READ AGAIN. WE HIT OVERALL STAINING BEFORE CAE!:
"In this population, patients receiving 0.1% RGN-259 had a statistically significant reduction in corneal fluorescein staining prior to entering the CAES on Day 28 when compared to placebo (p=0.034). "
SEE THE WORD, "PRIOR" to entering CAE.....we had total corneal staining P value of P 0.034.
That is a trial win! if the FDA doesn' require CAE, don't use it next time! Simple.
Restasis is a $1.5 billion drug and does not work that well and has significant side effects. Restasis failed it's first full Phase 3. Took that data and desiged the next one to pass. Liftegrast basically failed it's first Phase 3, technically, too! It took a second Phase 3, designd off the first...to make it for seemingly FDA approval soon.
What I get at is that the eye area has been a graveyard of drugs and trials. The FDA knows that and has loosened somewhat on their trial demands. Both Restasis and Liftegrast needed TWO phase 3's each to "get it right". This trial of TB 4 was technically a Phase 2b/3. we are following right along the same path as Restasis and Liftegrast. Nothing in this trial shows that TB 4 did not work....what it showed is were TB 4 works BEST.and interestingly, it is in the hardest to treat dry eye patients....not in the mild to moiderate cases. Weird. The Rodman analyst will understand this..and so will someone liek Novartis. The baby should not be thrown out with the bathwater on this resulst of TB 4. In reverse? the roadmap was just given for approval trial.severe dry eye. And Ora has said over and over, that their results are replaceable. They replcate what we got today in severe dry eye, TB 4 is a huge winner. But I sure woudl like to hear what I am thinking, from the Rodman analyst. Hope is research update comes soon.
and the next trial will focus more on severe dry eye! which RGRX clearly got a big win in!
Come on Rodman.....if he agrees with me and explains it in his client note, RGRX coudl be up on the day!