I need to get a more complete update and comparison for Phase 2,3 compounds in development, but another important data point is coming up for not pain, but hyaline cartilage regeneration.
I've posted a few times on TPX-100. If this peptide drug works, it will compete with stem cell technologies. There will still be need for pain management drugs. Regeneration will probably target patients that have the best hope of significant repair. KL4's and maybe even severe KL3's may be too damaged for that to be of much help. The study includes ICRS Grade 1-3. Obviously, a long way from a product, frequency and duration need to be measured, but it is the first test of a true DMOAD. Results are due soon.
"May 21, 2015—OrthoTrophix, Inc., a privately held biopharmaceutical company, announced today that the Company completed subject enrollment and all scheduled dosing in its Phase 2 clinical study of TPX-100 in subjects with bilateral osteoarthritis (OA) of the knee. ...One hundred fifteen (115) subjects have completed all scheduled intra-articular injections. The last subject’s last visit of the clinical site is scheduled in April 2016, and the study results are expected in mid-2016.
In fact this title is several weeks that go a lateral move. I was hoping it was like in the past ascended before the news but this time the big ones investors are more cautious, and if he comes to $ 5.5 is a lot. BW has done a very good discussion about other competing products. I also believe that there will be news about the result of PIVOT in late June early July
It's amazing how most readers haven't figured out that Bill Williams is a paid writer to alway subtly paint a negative picture about Ampion. It's very obvious when you go back and examine all of his negative posts.
I hear the Fed is watching him closely and the fund he works for.
Sentiment: Strong Buy
So this thing has completely halted. I've never seen a biotech stock be so flat for this long.
Anyone have an idea about when we might see some movement again? A few weeks before the Phase 3 release? A few days?
Progress of other OA therapies, GSK/MorphoSys compound is advancing, including hand-OA. I had discussed this some time ago at Phase 1. A key comment about difficulties in running a successful knee OA trial was made:
"If you try and do a trial in osteoarthritis in the knee or the hip it is confounded by weight, it is confounded by how much you walk, how much activity you choose to do and many, many other things," GSK R&D Chief Patrick Vallance said.
Apr 18, 2016:
The European multi-center phase 2 double-blind, placebo-controlled study will investigate the efficacy and safety of subcutaneous injections of GSK3196165 in 40 adult subjects with inflammatory hand osteoarthritis.
GSK3196165 is a HuCAL-derived antibody against GM-CSF (granulocyte-macrophage colony-stimulating factor) cytokine, a target molecule for a broad range of inflammatory diseases. GSK is currently developing GSK3196165 in two clinical trials in two indications - a phase 2b study in rheumatoid arthritis (initiated in Q3 2015) and a phase 2a study in inflammatory hand osteoarthritis (started now). MorphoSys has concluded a Phase 1 study in healthy volunteers, a phase 1/2 study in mild to moderate rheumatoid arthritis as well as a phase 1b study in multiple sclerosis...
MorphoSys received an immediate upfront payment of EUR 22.5 million. On achievement of certain developmental, regulatory, commercial and sales-based milestones, MorphoSys will be eligible to receive additional payments from GSK of up to EUR 423 million to total, in addition to tiered, double-digit royalties on net sales.
We have to be careful in comparing them since there are some differences: exclusion of KL4s (roughly 20% of Ampion study) but offset by no benefit for Ampion in KL2s. Ampion does currently appear to be the weaker of the 3 alternatives, but it also seemed stronger with more severe cases.
What is most probable outcome should Ampion/PIVOT succeed? All 3 will compete in the same market currently taken by Monovisc, Orthovisc, Synvisc,.. Other alternatives are close behind. Some will work better than others for different patients. Of course stem cell therapies will eventually supplant all, but that's some time in the future (5 years, perhaps longer). Even with a 20% market share of OAK with similar share of hand and hip applications and it's still a possible $1B company in perhaps 2017.
First, we need to predict the success of PIVOT and, frankly, I haven't seen any new data that suggests it could be less probable than SPRING. Then again, I thought the same about STEP. Problems occur and they are totally unpredictable, just as mishandling not caught by protocol, saline activity, higher dropouts in saline arm (Zilretta/Phase 2b), sampling/statistical errors, patient compliance,... ad infinitum.
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.