jd - The longer term pain relief is a critical factor. Injections are painful so having to be injected every 3 months is a problem. Even though STRIDE failed, it had some important longer-term pain relief data:
"The STRIDE study allowed inclusion of patients in all disease stages and demographics, which resulted in 67 percent of patients with severe disease (Kellgren-Lawrence 4) and greater body mass index than seen in comparable OA trials. Analysis of the STRIDE study results at week 20 showed an effect over baseline of 59 percent in K-L3 (p less than 0.001) and 31 percent (p less than 0.001) in K-L4 patients. That reduction in pain persisted and was not materially different at week 24."
31% is not considered clinically relevant. 59% is impressive (especially with that p value) for KL4s as STRIDE was comprised of 67% KL4s, many obese. So, competitively, it still required 3 injections vs a single injection for Cingal or Zilretta, but those studies did not include KL4 so comparison is not entirely clear.
if the annoying yahoo filters will allow posting the rest of the competition statement...
We believe that other programs, such as Orthotrophix?s TPX-100, Merck Serono?s FGF-18, Abbvie?s ABT-981, Menarini?s MEN16132, #$%$-A?s DA-5202, Mariel Therapeutics BMP-7, Samumed?s SM04690 and Allergan?s (bot-tox), have not yet entered Phase 3 clinical trials. Autologous cartilage transplantation products, like Carticel, are appropriate for focal defects in cartilage, not the kind of diffuse disease that is seen with OA. ...Stem cell approaches to OA are being explored, but these are earlier in development...
Still a month to go. It jumped fast throughout Apr. pre-STRIDE results also had a good run a several weeks before the plunge. Hopefully it will repeat at least part of if this time.
STRIDE had STRUT interim data supporting it so there may have been more confidence that STRIDE would work.
From the Dec 2015 FLXN 10K (Zilretta competion statement). Since that time Cingal has been approved in the EU and started distribution in Canada.
In addition to marketed IA medications for OA, other companies have OA product candidates in advanced stages of clinical development.
• Anika Therapeutics, Inc.’s Cingal, which is a mixture of Anika’s Monovisc and a low dose of a commonly used immediate-release steroid. Anika filed a Pre-Market Application with the FDA for Cingal based on a single pivotal clinical trial. In December 2015, Anika announced that due to the steroid component of the product, it will need to file this product candidate under an NDA.
• Carbylan Therapeutic’s Hydros-TA, which is a mixture of Carbylan’s own HA and a low dose of a commonly used immediate release steroid. In February 2016, Carbylan announced that Hydros-TA met only one of its two primary endpoints in its first Phase 3 study.
• Actavis plc/Hanmi Pharmaceuticals Co., Ltd.’s HA product Hyalrheuma, which is an HA preparation.
• TissueGene, Inc.’s Invossa, which is a combination of human allogeneic chondrocytes and TGF-b1 transfected allogeneic chondrocytes. Invossa is currently in Phase 3 clinical studies.
• Ampio Pharmaceuticals, Inc.’s Ampion, which is a derivative of human serum albumin, is described as having anti-inflammatory properties, and is formulated for immediate-release. Ampion is currently in Phase 3 clinical trials.
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).