2024 Update on Interventional Orthobiologics Studies and Product Pipelines
Interventional orthobiologics research continues to advance at a furious pace. Last year, I published a blog that attempted to look ahead a bit at studies and products that may be available and posited a timeline for when that could happen. This year, I went deeper to search product studies/FDA trials and some key research studies that could impact the field.
Why Is Any of this Important To Physicians and Patients?
I focused here on finding studies that could change the field or alter or confirm what providers do daily with orthobiologics. For example, if a company gets FDA approval for SVF, that could dramatically change the practice of someone who uses BMC. If a company gets FDA approval for culture-expanded umbilical cord stem cells, that could change many practices. Finally, if a pharmaceutical company gets approval for a knee OA injectable drug that reduces disease progression, that could change everything.
Where Did I Get this Information?
I searched www.clinicaltrials.gov for studies that used mesenchymal stem cells, stromal vascular fraction, bone marrow aspirate, bone marrow concentrate, Mfat, and exosomes. I searched through disease-specific filters like knee OA to find pharma drug trials. I waded through about a thousand hits in total.
I excluded a few smaller studies that were pilots in areas where much has already been published. I also excluded clinics merely discussing that they would track outcomes and focused largely on randomized controlled trials and comparison studies.
I have indexed these studies by their reported year of completion. However, whether any study will be completed by this date is unknown.
THE RESEARCH
Key:
BMC=Bone Marrow Concentrate (the same as BMAC or Bone Marrow Aspirate Concentrate)
BMA=Bone Marrow Aspirate
MFat=Microfragmented Adipose Tissue
SVF=Stromal Vascular Fraction (digested adipose tissue to liberate stem cells)
MSC=Mesenchymal stem cells-in this context this means that the cells have been isolated and culture expanded.
2024
Ingeneron – Wrist OA 40-patient SVF study with an estimated completion date of 3/31/24 with a steroid comparator.
Mayo Clinic – 30-patient study using SVF for knee OA to be completed on 12/24.
GID-BIO -124 patient study with knee OA to test SVF versus a placebo. Estimated completion 12/30/24. This is likely an attempt at an approval study, but it remains to be seen if the FDA will approve an SVF device with this small of an n.
Lipogems – US Military-Mfat to treat meniscal injuries with an enrollment of 80 patients. Estimated completion 9/30/24.
Lipogems – Mfat vs. corticosteroid knee OA study with 173 patients (phase III), estimated completion 12/31/24.
SyntrFuge – Mfat Knee OA study with 173 patients, estimated completion 12/24.
Joint-Stem – Adipose MSCs for knee OA versus placebo. Phase 2b/3a (other studies published from Asian approvals)-140 patients, estimated completion 12/30/24. A phase 2 with 28 patients was previously completed. This phase III is unlikely to be the final trial required by the FDA.
Mayo Clinic – 24-patient study on adipose MSCs for hip OA. The estimated study completion date is 12/24.
Lipogems – MFat hip OA study with 30 patients, estimated completion is 9/24. (Rizzoli Institute in Italy)
Via Disc – Small 35-patient trial on patients with DDD injected intradiscal with an expected completion date of 7/31/24.
Via Disc – Small trial on 35 older patients with DDD injected intradiscal with a completion date of 12/31/24.
Cleveland Medical Center – Phase 1 trial (16 patients) on autologous BM-MSCs for knee OA, expected completion 7/24.
iSCLife – 242 patient study using umbilical-derived MSCs to treat discogenic pain with an estimated completion date of 12/31/24. China.
BMMMU – 84 patient study using adipose MSCs to treat knee OA with an expected study completion date of 9/30/24. Pakistan.
Yantai Hospital – 60 patient single-blind study using culture-expanded adipose MSCs to treat knee OA with expected completion of 12/24. China.
Marrow Cellutions – Small 30-patient study of BMA used to treat shoulder OA with an expected study completion date of 9/10/24. Italy.
Rizzoli Institute – Long-term follow-up of 60 knee OA patients who received either BMC or HA injections with a study completion date of 7/24. Italy.
Xijing Hospital – Small 30-patient knee OA study of adipose SVF with a study completion date of 12/30/24.
Paradigm Biopharma – Phase II/III with 938 patients with different injection frequencies versus saline-completion date of 12/6/24.
Mayo Clinic – Intra-articular dextrose prolotherapy vs. placebo for knee OA in 160 patients-completion date of 3/24.
Novartis – LNA043 (cartilage repair stimulator through integrin binding) is being tested with canakinumab (1L1-b monoclonal antibody) in 138 knee patients in a phase 2 trial to be completed 6/25/24. Australia.
UCLA – IRAP vs. saline in 32 ACLR patients to reduce post-surgical knee OA-phase 1 to be completed 5/30/24.
2025
Stanford – 40 patient MFat study on knee osteoarthritis-estimated completion is 3/26/25.
Stanford-48 patient study on MFat for treating shoulder osteoarthritis- estimated completion is 12/31/25.
University of Utah – Amniotic fluid versus steroid for the treatment of knee OA with 60 patients. Estimated completion is 7/30/25. Phase 1/2.
Biorestorative Therapies – Autologous MSCs (hypoxic conditioned) injected intradiscal for DDD versus saline with 99 patients. Estimated completion is 8/31/25. Phase 2.
Atrocell – Phase 3 trial using allogeneic MSCs versus autologous MSCs versus control HA injections in 120 patients. Expected completion 12/25. Spain.
Turkish Grant – Phase II trial using MSC-derived exosomes in 30 patients with degenerative meniscal tears, estimated completion date of 3/25. Turkey.
Meridigen Biotech – Phase 1 trial of 6 patients with knee OA treated with umbilical cord MSCs with a study completion date of 6/25. Study in Taiwan.
University Medical Center-Ljubljana – Umbilical cord MSCs for treating severe knee OA with 30 patients. This study analyzes pain/function and synovial fluid composition in patients undergoing TKA with samples and an outcome endpoint just before that surgical procedure. Expected study completion is 3/31/25. Slovenia.
Rush University Medical Center – An injection of BMC after meniscectomy versus no such injection in 100 patients looking at the progression of OA over time. Expected completion date is 12/31/25.
Pagdin Health – 240 patient study in major joint arthritis that compares MFat+PRP vs. MFat vs BMC as a phase II. The estimated completion date is 12/25. Canada.
Centeno-Schultz Clinic – BMC to treat CCI in 80 patients with an estimated completion date of 6/25.
Lipogems – MFat vs. saline for the treatment of knee OA in 173 patients with a study completion date of 2/28/25. This could be duplicative with the 2024 MFat vs. corticosteroid study listed above as both curiously have the same n and are testing the same device. This entry also has two separate and identical entries at different US sites.
Tissue Gene – Chondrocytes over-expressing TGF-beta vs. saline used to treat knee OA in 510 patients (phase III) completing 8/30/25.
Novartis – MMP inhibitor injected subQ in 98 knee OA patients versus placebo-completion date of 10/6/25.
Spa Farma – Clodronate vs. saline in 296 patients-completion in 10/25. Italy.
Rizzoli Institute – Hydrolyzed collagen injection versus placebo in 204 knee OA patients-completion 12/25. Italy.
Mayo Clinic – A2M plasma pilot study of 20 knee OA patients to prepare for a larger RCT-completion 12/31/25.
GSK – GSK3858279 (antibody against chemokine CCL17) in 420 knee OA patients as a phase 2 trial with a completion date of 10/20/25.
2026
Ingeneron – Pivotal study of Rotator Cuff Teras using an adipose SVF device-IDE study completion at 246 patients now slated to be completed 2026-pushed back from 2024 in my last 2023 update. There was a smaller study with 168 patients completed on 12/31/23, which seems to be a part of this larger 246-patient study. Both studies are using a steroid comparator.
Organogenesis – Amniotic membrane suspension versus saline for knee OA in 474 patients (phase 3). Estimated completion 3/26.
Personalized Stem Cells – 260 patient study with SVF used to treat knee OA, estimated completion is June 2026. Given that this study is not yet listed in www.clinicaltrials.gov and was only reported by the company, this may be an optimistic time frame for study completion. This does not appear to be a final phase III study for approval.
Cellkine – Phase II allogeneic culture expanded BM-MSC injections for 40 painful lumbar facet joint arthritis patients. Estimated completion 7/2026.
Rush University Medical Center – BMC vs. corticosteroid in 100 knee OA patients with an estimated completion date of 3/31/26.
Elixcyte – Allogeneic adipose MSCs versus saline for knee OA as a phase 3 trial in 160 patients-completion date of 6/26. Taiwan.
CellTex – 300 patients twith shoulder, knee, and hip OA treated with adipose MSCs listed as a phase II, but it is difficult to say whether this study is a clinical trial as I see no description of placebo arms. Completion is 8/15/26.
2027
Rizzoli Institute – Comparison of BMC vs. HA for treating ankle osteoarthritis in 120 patients with an estimated completion date of 7/27. Italy.
Rizzoli Institute – Comparison of BMC vs MFat in knee OA and 204 patients to be completed in 1/27. Italy.
2028
Karmy Clinic – Phase 2 to compare BMA versus MFat for the treatment of hip and knee OA with 400 patients. Expected completion 8/8/28. Canada.
Genesence – Phase 1b with 50 patients testing adenovirus vector gene therapy inhibiting IL-1 on knee OA.
Notes on Companies Likely to Launch Studies in This Time Frame
Discgenics is a company that uses chondrocytes injected into the intervertebral disc. It completed a 60-patient phase 1 US study on 11/10/22. In November 2022, it completed a phase I/II study in Japan with 38 patients. Given that I believe it is still active in the DDD space, we’ll likely see a phase II US study launched in 2024.
Notes on Companies That May Have Flamed Out
No study is guaranteed to produce great results. In addition, companies pull out of the FDA trial arena for all sorts of reasons, often financial.
CellTex seems to have dropped out of the clinical trials game. Last year, they had multiple studies around phase 2; this year, an entry on www.clinicaltrials.gov looks more like registry tracking than an FDA-approved trial.
The Mesoblast study of Rexlemestrocel-L with 404 patients was completed in 2022. This tested four different groups based on dose and adding HA or not. The Mesoblast website has no information on whether this phase 3 trial was accepted by FDA for a BLA. I had previously reported on the underwhelming results of the mesoblast lumbar DDD product. After reviewing company data on the www.clinicaltrials.gov website, they are still playing the “responder analysis” game I have previously reported, with only 30-40% of patients being “responders.” Hence, it looks like this product, based on what I can see, is not commercially viable.
More Possible Activity Based on Industry Experts
I asked Cade Hildreth and Lance Breastgoff of Bioinformant, who are commercial experts in the orthobiologics space to review my list and see if I missed anything, and this is what they came up with:
- Cynata Therapeutics is advancing trials with its iPSC-derived MSCs. Most aren’t focusing on OA, but this one is. Looks like their most recent update is from Nov 2023.
- Organicell completed a Phase 1 study in knee OA with their Zofin (exosome) product, but we haven’t heard anything about it progressing further, so I’m not sure what’s going on there.
- Cells for Cells is starting to dabble in exosome therapies for OA, but it looks like they have only treated one patient.
- Exostemtech is trying to advance its exosome product, EST-P-EXO1, into trials in Korea but there haven’t been any updates since this one.
- Ageless Biotech got an IND for treating knee OA using minimally manipulated adipose-derived stem cells, but it doesn’t look like they’ve updated any progress in quite a while.
What’s the Reader’s Digest?
The companies trying to get FDA approval for a Stromal Vascular Fraction adipose device aren’t likely to get those approvals soon. I would estimate that it will be 2027 or 2028 until we see those devices on the US market.
The same holds for companies offering culture-expanded MSCs. I wouldn’t expect to see any of those being approved in the US until the very late 2020s.
Italy’s Rizzoli Institute is conducting cool research on already cleared or exempt US orthobiologics. I look forward to seeing the results of those studies.
Big pharma is conducting large studies on various disease-modifying osteoarthritis drugs. One or two of these could be on the market by the late 2020s.
The upshot? There will be quite a bit of research on many orthobiologics published here in the next few years! I, for one, look forward to having many options blessed by the FDA that I can use in my patients.
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