SPRING had an ad hoc 20wk point for a small set (36 vs 28 control). Pain reduction vs baseline was 45% vs 30% for saline.
Cingal 26 wk pain reduction was impressive though one has to be careful even using percentage drops relative to baseline because the Cingal study used WOMAC/VAS rather than WOMAC/Likert. However, the Responder Rate is directly comparable and for CINGAL was 92% (26 wks) compared to Ampion/SPRING was 79% (12 wks). Zilretta is up next.
Zilretta Phase 3 had a 52% pain reduction at Wk 12. Slide 5 of the "Zilretta Phase 3 Additional Slides" off their website shows the trend back towards baseline at 26 wks but still impressive and there is a strong, highly statistically-significant separation at the 12 wk endpoint (p lt 0.0001). The OASRI presentation shows Phase 2b age ranges 41-79 and KL2 (44%) KL3:56%. Importantly, the Mean Womac Pain score for the baseline was the same as Ampion: 2.2. SPRING had 26% KL4 in Ampion arm, 19% KL4 in Saline arm
So, even though KL4's are not included, the average amount of pain at the start of the trial is the same. The range was huge: 0-3.6. The scale goes from 0-4, so a few people were in extreme pain and a few very mild, even though they had X-rays confirming at least KL2. Phase 3 numbers are similar. BMI's were about 30 kg/m2 (overweight: 25-30, Obese 30-40). SPRING avg. BMI was 10% higher (33).
Bill, thanks for providing the pain numbers. In order to refresh my memory, I had to take a quick glance at AMPE's 10-K. Ampion, in SPRING, produced 40% reduction in pain at 12 wks. and 64% reduction in STRUT Phase 2 (multi-injection) at 20 wks. As I recall, AMPE hasn't released a pain number beyond 20 wks. And PIVOT is 12 wks. So, 72% at 26 wks. appears to be a high hurdle.
ANIK launched CINGAL sales in Canada yesterday. It received European approval earlier this month so can be expected to start sales there by YE. It requires another trial for FDA/US approval.
The 13-01 Phase 3 trial had 72% pain reduction with a single injection at 26 wks with good statistics (p less than 0.01) and a 92% responder rate.
Agree, though they certainly have access to the blinded data. They used blinded data to issue an interim report for Optina, but I'm certain that won't be done here. If the separation between placebo and drug arms was greater in SPRING or the KL2 percentage was lower it would at least provide more qualitative assurance. The WOMAC Likert pain subscale (0-4 points*5 questions, reported as the avg.) is subjective so even the same person receiving the same treatment (placebo/drug) can score differently on different days. Arthritis care & research. 2011;63(0 11):S208-S228.
I am not sure, and if someone knows better I would also like to see the analysis, but with out at least some blinded data points from the current trial any inference would be based purely on historic data and relatively useless in figuring values with enough relevance to the current trial to matter one way or the other.
If we had at least some blinded data that showed separation someone could use historic saline efficacy data, data from the ampion trials and throw in if one wanted the likely hood that any of the new protocols will affect those outcomes and infer the probability of getting the desired p-value or better with the given blinded separation data.
but as far as i know they have no intention of releasing interim data so i think we will just have to wait and see.
Is early June based on est. Pivot end? I had early/mid-July.
Yeah, most of those comments are frustrated cheerleaders. They have no merit, substance or relevance. They obviously weren't around when I interpreted the STEP disaster as a trial failure, not a drug failure, based on facts or reasonable extrapolation from known facts.
The only point of relevance is the estimate of PIVOT success based on current protocol (as publicly disclosed in Clinical Trial and CC statements (such as background checks on all personnel following the suspect high saline efficacy that caused STRIDE to fail)) and SPRING (per PLoS One paper). Any *intelligent* conversation about cohort mapping and p-values from SPRING to PIVOT using Bayesian or other analysis would be welcome. Then again, there is always the unknown issue lurking. That's the nature of drug development. It's not fully predictable.
I think 13G/A's should be available soon, assuming any changes were made.
I agree, Bill's position, short or long is irrelevant, he makes reasonable assumptions based off of available information, which is all anyone can do, and what anyone invested should have already done for themselves.
The fact of the matter is this is a high risk play, even after a successful trial (though it will significantly de-risk the investment if the trial is successful) and BIll's acknowledgement of that just shows that he understands his risk/reward. I personally believe the reward is worth the risk, and apparently so does Bill. but that's for everyone to decide for themselves after having done there own due diligence.
Bill - Maybe our court jester will say I am you as well. Anyway I do not care. Thank you. Looking forward to a trip to Denver in early June and expect a sit down with MikeMac.
Ben detto. Ci sono molti cheerleaders idioti che non sanno nulla della malattia o lo sviluppo di farmaci . Non possono vincere un argomento razionale #$%$ base di fatti in modo che ricorrono ad odiare ed etichettare i non cheerleaders come pantaloncini . Sono pazzi .
A parte che non ho capito una minchia di quello che hai detto. Io sono ITALIANO e ho investito in AMPIO. Qui in Italia non esiste LONG o SHORT e onestamente non me ne frega una sega. BW è molto gentile e preparato e quando ho bisogno di delucidazioni mi da sempre risposte interessanti. Dunque smettiamo con tutte le cazzate avete in questo forum, sempre a complottare che uno abbia due/tre alias.......
pironio, are you Bill Williams under a different alias or does he pay you? Clarity is not what Bill is about. Fancy double talk designed to confuse and muddy the waters is his m.o.
Don't forget he is an analyst paid by the shorts and has posted thousands of times on this board as well as others. He has never denied his affiliation with the shorts.
His occasional bow to being long is laughable.
They are in 2 different situations. FLXN is getting ready to file NDA for Zilretta, has an ATM (like AMPE) and has started a Phase 2 for OAK in diabetics (compare to AMPE with hand-OA). Zilretta has 505b2/BreakThrough status from FDA which means a 6mth NDA review instead of 9-10mth. They just announced they expect filing the NDA later this year, assuming the pre-NDA goes well. The Phase III data is solid and Phase 2b only failed due to dropouts in the saline arm (it didn't relieve pain as well as Zilretta, but statistics suffer because of dropouts). FLXN has A LOT OF SMART MONEY behind it. Look at long list of institutions as well as the pharma co investment from NOVO. But, it does not have a SPA guaranteeing that the FDA won't demand another trial, so there is risk. Still, it likely went up because of the 10Q and conference call stating that management believes the pre-NDA will go well since the data is strong. Some of the better posters think the company will be sold shortly after the NDA is submitted or approved (Q2, 2017).
AMPE is in a higher-risk, wait-and-see mode. The last 2 Phase 3 trials failed and the last Phase 2 was terminated before the 52wk endpoint was reached that hoped to show cartilage improvements. It does not have as many strong backers as FLXN. Not certain I'd call 7% a rocket though. FLXN didn't exactly double, etc. after positive Phase 3. It was $20 at the beginning of the year and only $13 after Phase 3 success was announced. I'd expect similar behavior from AMPE, if successful, though it's by no means guaranteed. There is a very large short position in AMPE (15% vs 6% for FLXN).
Indeed. There is a company focused on the area: GALT. They just recently released positive Phase 2a results for plaque psoriasis. So, compounds and a discovery platform exist and have an experienced management team with successful trials in multiple indications. They haven't done galectin-1 to my knowledge. I remember when UGa founded the Carb Center. Good to see it progress this far.
Wish they'd unload it too, but you are correct: their estimation of value is likely unrealistic and it's only worth what someone else is willing to pay. With equal or better pain relief with Cingal and/or Zilretta and no demonstrated healing from Ampion, making a case for higher value from a partner is difficult.
If FLXN's price didn't move with a successful Phase 3 and FastTrack + 505b2 it's possible AMPE won't either. Maybe short covering would be enough to push it to the teens before it drifts down again while the BLA is submitted and processed. They are a long way from any revenue w/o a sale or upfront cash in a partnership. Cash runs out before the BLA process is done.
Just wish there was more evidence to increase my confidence that this trial will succeed.
You will see his sentiment change as the PPS begins to ramp up. Last year when AMPE was rising before STRIDE failure, BW was the biggest basher on this board and an obvious short schill. As soon as the stock tanked post STRIDE, he took a 180degree turn and all of a sudden became the "voice of reason" on the board and a self decsribed ally of the longs. Just watch this dude in the couple months...