The FDA just announced it approved the cell therapy Omisirge from Gamida Cell for severe aplastic anemia (SAA). This is the first cell therapy approved for SAA.
SAA is a rare, life-threatening blood disorder. It is often treated with hematopoietic stem cell transplants or immunosuppression. There’s a major autoimmune component to the condition.
The FDA approval here is likely part of a growing trend in the last few years. Moving forward, I believe we’ll see the agency ask for even less data for approvals. There are potential pros and cons to that. Let’s talk about the Osimirge case as an example of the broader trend.
Omisirge for SAA, approval with limited data
The approval of Omisirge, also known as omidubicel, was based on a very limited amount of clinical trial data.
While Gamida Cell (now owned by privately-held Ayrmid Ltd) had already received approval for use of Omisirge for some blood cancers, I see little data specifically for SAA. For reference, you can see my full list of FDA-approved cell & gene therapies.
As best as I can tell, this approval was based on a very small, single-arm, open-label Phase I/II trial. The FDA has granted a handful of other such low-data approvals, often in the cancer space, in the last few years.
It’s also interesting that the National Heart, Lung, and Blood Institute (NHBLI), Gamida’s collaborator, was the trial sponsor. Here’s the trial listing where the drug was called Cordin.
Why the FDA approval?
Readers of The Niche may recall that I tend to hope to see fairly extensive data before the FDA approves drugs including cellular therapies. However, there may be solid reasons to have approved Omisirge for SAA without a Phase III trial and with so little data on so few patients.
People with SAA have relatively high mortality. There are also few treatment options. Matches for HSC transplants can be difficult to find. Another factor is that as a rare disease there are so few SAA patients that running large, placebo-controlled trials could be quite difficult or impossible. Such factors must be considered.
Even with all of these things in mind, this approval carries sizable risks for both patients and the FDA. Small studies (just N=14 here for this investigational cell therapy) with single-arm designs don’t have much power.
The big concern here is that such studies can overestimate benefits and miss side effects.
What are the data like in this case?
The data on Osimirge for SAA
Here are the initial results I could find in a press release:
“Interim results from the study, led by Dr. Richard Childs of the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH), were highly encouraging, with 13 of the 14 patients (92.9%) reaching rapid neutrophil recovery, with a median recovery time of 7 days. The disease-free survival rate, as well as overall survival, was 92.3%, comparing favorably with outcomes from patients who receive transplants from matched donors. Additionally, no severe (Grade III–IV) graft-versus-host disease (GvHD) or chronic GvHD was observed, and only 14% of patients experienced moderate (Grade II) GvHD.”
These sound encouraging. I’m sure the data were compared to historical data, where SAA patients generally do much worse on neutrophil recovery, recovery time, disease-free survival, and definitely with GvHD.
From the FDA announcement:
“Omisirge is a novel stem cell product from umbilical cord blood that will be able to offer a therapeutic option for patients with severe aplastic anemia who have limited options for stem cell transplant,” said Megha Kaushal M.D., M.S., Acting Deputy Director of the CBER Office of Therapeutic Products and pediatric hematologist. “Omisirge will shorten time to neutrophil recovery which leads to shorter recovery times after transplant and may improve infection rates in this patient population.”
I hope this holds up as the cells are given to many more patients.
There are also side effects to consider. From the FDA: “The most common side effects associated with Omisirge include febrile neutropenia, viral and bacterial infections, hyperglycemia, immune thrombocytopenia and pneumonia. Autoimmune cytopenias have occurred in 25% of patients.”
Overall, was this a wise drug approval?
Do you think this a good move by the FDA?
I’m still trying to answer that for myself. As I said, I tend to want to see far more data, but SAA patients need options and this drug seems hopeful. The risk-benefit ratio here might be justified.
Still, it strikes me how this approval seems to strongly contrast with CBER Director Vinay Prasad’s views on how much data should be needed for approvals of other products including vaccines and gene therapies, where he has been quite harsh at times.
I just wrote over at STAT about FDA leadership contradictions: FDA drug center’s new acting director fits a pattern of risky, internal contradictions among agency leadership. The FDA also announced this week that in general fewer trials will be required for drug approvals moving forward.
Taking it all together, we’re going to see more approvals based on limited data including for some cell and gene therapies.
Some approvals are likely going to make sense, while others could be swayed by politics so we have to carefully watch this space and discuss developments.
Hi, Paul:
Can you comment on whether anyone can tell whether Gamida Cell’s cell therapies (all of them) are only progenitor cell treatments, as opposed to their representation as “stem” cell treatments? Their trial endpoints never include long-term engraftment; and as far as I can tell from publicly available reports, they have not confirmed expansion of hematopoietic stem cells in their products preclinically (i.e., by SCID mouse assays). No doubt that the short-term effects on neutrophil recovery and lowered infection rates are beneficial for both cancer patients and SAA patients, but without longterm engraftment data, there is no confirmation that their treatments correct the underlying problem compromising the health of these patients. Perhaps they call them stem cell therapies prematurely?
James @ Asymmetrex®
I thought the starting point is stem cells, but I’m not sure what’s the composition of the final product.
More generally, there seems to be some acceptance in the field of calling products that began with stem cells (e.g., iPS cells) by the “stem cell therapy” name even if the final product is somewhat or fully differentiated.
Yes, that is what I meant to ask.
Your response leaves me more confused. As a long time reader of your blog, you have made it very clear that you do not approve of doctors selling unapproved therapies and taking advantage of patients. You have also stressed that therapies should go through the appropriate pathways to get approval before being available to patients.
Case in point. You have a company who has done all the right things. They conducted what appears to be a very promising trial and got FDA approval. It was also for a fatal indication with unmet needs. Shouldn’t you be celebrating this? Am I missing something? Now you say it’s low-data??? By what standard? Have you reviewed their CSR? In a condition like this, I have no problem with an open label trial. You already have plenty of real-world data to tell you what would happen left untreated. A small sample size is often to the detriment of the sponsor. It is harder to show efficacy in a small cohort. In this case, they showed clear efficacy and safety. If there is something wrong with the analysis of the data, please present it.
Your headline is insulting. You insinuate that FDA is lowering their standards. To the contrary, they are finally doing their job and exercising some common sense.
It’s not insulting and wasn’t meant that way. It’s just reality that there’s apparently not much data here for this cellular drug for SAA compared to what most other sponsors have to supply from all the way through Phase 3 with placebo controls, blinding, etc.
If you look at my post, I talk about why this approval might be justified despite there not being tons of data.
Based on what I’m reading here, absolutely. The potential benefits outweigh the risks – irrespective of how “preliminary” the data might be.
However, FDA must evaluate clinical data regularly to assess safety and efficacy. There are many instances where products receive conditional approvals and their status remains that way for years despite a lack of real world efficacy and in the worst cases, devastating safety issues.
Dr. Knoeplfer – Innovative products will have preliminary data. It has been my observation that you are averse to unapproved products of any kind. So is it accurate to say that you do not believe innovative products should not be available and accessible to patients outside of a clinical trial? Would your answer be the same if you were a terminally ill patient?
Just so we’re talking about the same thing: Innovative – adjective, (of a product, idea etc.) featuring new methods; advanced and original. Source: Oxford Dictionary
@Stemcelllady,
Can you clarify what you are asking here: “So is it accurate to say that you do not believe innovative products should not be available and accessible to patients outside of a clinical trial?” Did you mean to say “you do believe”?
For me it’s about good data rather than an approval by the FDA or other similar agencies.
Low-data approvals like the FDA OK’ing Gamida’s product for SAA can also make sense. We just have to realize that such approvals come with risks because there’s so little data, but patients need a therapy for a sometimes lethal disease.
To me it makes less sense to take risks on biologics (e.g., the “stem cells” offered by clinics) with little data if there are already alternative therapies and/or the conditions in question isn’t life threatening or otherwise very serious.
There are instances where biologics like PRP and unmodified bone marrow don’t require FDA approval. These are widely used for all kinds of applications. In my view, it’s not really approval that is needed in this particular space (PRP, marrow aspirates) but a lot better data.