Yeah I'm not sure about LNA043, it's hit and miss as far as I can tell.
They seem to be specifically targeting cartilage in the knee in their studies7. It doesn't sound like a holistic approach and even there is some discussion of the results working but in very specific tissues/compartments. I can't seem to find a lot on how well it addresses pain and stiffness.
Info is a bit scant...but happy to be corrected:
1) I believe they are currently in a Phase 2. They have had some other Phase 2 studies with one being cancelled 3 and results seem very mixed to me!
2) Example of Mixed data:
Here is what they present in their patent 1:
Table 50 depicts mean cartilage thickness as measured by MRI for three dosing cohorts and a placebo group.
Table 50. Mean cartilage thickness by MRI at Week 12
You want thickness to be increased! Only the placebo increased (!?). Their higher dose (0.23mg) was slightly worse than their medium dose.
How do we compare?
We were right on SS (0.05) though our patient numbers were anemic (15) and came in at plus 0.17 mm, placebo went the other way.
3)
As a result of their Phase 1 this was the discussion:
MRI was the primary method utilized to examine bone marrow edema (BME), which the FDA defined as a safety outcome in this phase 1 trial. BME stayed the same for most subjects from baseline to Week 12. For some subjects in both treatment (N=4) and Placebo (N=3) groups, BME worsened (none to focal). 4 subjects in the treatment groups showed improved BME results (focal to none and diffuse to focal). These interim BME imaging data suggest that a single intra-articular injection of the compound of Formula (I) into the knee of OA subjects appeared to have no appreciable effect compared to Placebo.
Not glowing by any angle...
Maybe their results in the Phase 2 will be better?
Finally it is intra-articular and it in a monoclonal antibody which has it's own set of problems/disadvantages.
Anecdotally I heard they were attempting to have a shoulder trial but they couldn't get recruitment numbers so the aren't pursuing it.
4)
I believe the dosing regime was 4 once weekly in the below study? 5
In the current Phase 2 I believe it is on once in 6 or 12 month cycle over the 5 years they are studying it over.
To me that's fairly onerous, it is intra articular.
5) I believe they have some sort of interim read out due soon, their slated end date for the whole Phase 2 is slated sometime in 2027. By then I would hope we are selling into at least one market?
We will have to keep an eye out on this one nevertheless.
Will be interesting to see what their WOMAC pain read out is like.
DYOR
ps: Goldmad, I re-read one of your competition posts, it was really good, you should do an update sometime.
Here is a link for anyone interested:
https://hotcopper.com.au/threads/paradigm-competition.7707229/?post_id=70978333
APPENDIX
Here is what I wrote about LNA043's presso at CTS in 2023 in Denver:
------------------
Novartis - LNA043
Matthias Schieker
Update on currently recruiting studies. Two divisions ; Early and late stage trials. Today - Early Trials discussion - 30 OA trials until 2015.7000 patients in late stage that have failed until 2015.
Currently running 5 compounds in 6 studies. We have approx 1000 patients in studies today. We are highly committed to turning this around and developing drugs in OA.2 Year study - trying to find the population where the drug has an effect.
Canakinumab - Anti IL1. 138 patients - enriching the study for synovitis - study is ongoing. Regenerative Compound - small study to understand anabolic imaging In licensed compound from Merck - Pain endpoint, DMOAD investigation 98 patients, study has just started recently Nrp3 inhibitor Anti Inflammatory compound.
Need to really know the MOA's. Anabolic treatments need to be much better
Mozz Notes
®
This speaker didn't really touch on the data or how the various trials are actually going. The speaker did give us a story which became a bit of an insight :
"
When I was in medical school 25 years ago, the first Tnf-alpha inhibitors were introduced for RA patients, when I was a resident Bisphosphonates were established for osteoporosis. When I was a Professor at University, I helped launch Denosumab for osteoporosis (A biological) and I still hope we can manage to solve the OA problem. I think there are so many parallels with regards to RA to Osteoporosis to OA...and I do hope that before I retire someone has managed to come up with a treatment for OA. I do think it is ready to be there." .
PROS
Seems like there is some good data with this drug despite also having some past concerns?
CONS Intra-articular.
Serious and sometimes fatal infections may occur during treatment with canakinumab.
4
Immunosuppressant.
TIMING: Approx Oct 2025.
-------------------------------------------------
REFS
1)
https://patents.google.com/patent/WO2017079765A1/en
2)
https://regenexx.com/blog/2024-upda...orthobiologics-studies-and-product-pipelines/
3)
https://www.pharmaceutical-technology.com/data-insights/lna-043-novartis-net-present-value/?cf-view
4)
https://clinicaltrials.gov/study/NCT04864392#study-plan
5)
https://www.oarsijournal.com/article/S1063-4584(22)00310-7/pdf
6)
https://www.yankemd.com/pdfs/novartis-cartilage-injury-brochure.pdf
7)
https://www.hra.nhs.uk/planning-and...ication-summaries/research-summaries/onwards/
(20min delay)