Julian Adams, PhD, discusses the potential of Omidubicel for patients with hematologic cancers such as lymphomas and leukemias.
GeneTherapyLive® sat down with Julian Adams, PhD, chief executive officer of the biotechnology company Gamida Cell, to discuss updates with the company, its latest innovations in cellular manufacturing, and the development of omidubicel (NiCord), which may help to resolve unmet needs in patients with hematologic malignancies.1
Although use of cord blood has been a successful tool in the treatment of leukemias and lymphomas, the number of cells collected from infants is not enough for an adult transplantation. However, Omidubicel has the potential to expand stem cells 50- to 100-fold with high reliability manufacturing.
Gamida Cell is dedicated to innovative cellular therapies. Cell and gene therapies have blossomed over the last decade into potentially curative treatments for blood cancers and serious blood disorders. We have been part of that innovation and are developing multiple products to help patients with terminal diseases [who] either need a bone marrow transplant or some other treatment for a serious malignancy.
Our “special sauce” has been in our unique perspective and platform technology to grow cells. We deploy what is called nicotinamide tumor cell culture [NAM], so that when we add the growth factors to enhance the number of cells, we retain the property of those cells, namely the function and potency, [but] we make larger numbers of cells. We can get a 50- to 100-fold expansion of a cell with a specific phenotype, but it retains its original property by adding this NAM technology to the subculture system. We have been doing this since inception and have successfully developed 2 critical programs that are showing remarkable activity and signs of efficacy with safety.
Of course…we are still [in the] pre-approval [stage], but I wanted to make the point that over many years, we have developed extreme expertise in cell culture and cell manufacturing on different scales. As well, we have learned how to cryopreserve those cells because they often need to be shipped; they are not stable if they are not frozen at very low temperatures. We can recover those cells through bowing procedures that we have developed both through thawing buffers or standard operating procedures.
Omidubicel is designed as a unique, personalized bone marrow graft—a stem cell graft for bone marrow transplantation—in patients with serious leukemias and lymphomas who are in remission but are at a high risk for relapse if they do not get a bone marrow transplant. The unmet need here is that many patients cannot find a suitable match in the adult registry because of ethnic diversity and [because] genetic matching is challenging. Not only that, but time to search and finding your match can take 2 to 3 months and patients may not have that time before they relapse and become ineligible for transplant.
Omidubicel solves that problem in several ways. Our starting material is core blood, [which] is the youngest source of stem cells you can get—it comes from a newborn. They are very naïve, unadulterated, and the purest stem cells that you can find. In addition, they have very naïve T cells, so that you do not need a perfect genetic match. A 4 out of 6 human leukocyte antigen match or genetic match is sufficient if your starting material is cord blood. This has been known for 3 decades. The only limitation of cord blood is the number of cells you can get from a newborn is insufficient for an adult transplant.
What we have done is develop a technique using the NAM technology to expand those stem cells so we can make 50- to 100-fold more stem cells that we can manufacture with high reliability for patients in need of a bone marrow transplant. Over the past 8 or 10 years, we have done rigorous clinical development, starting with a phase 1 study, a phase 2 study, and then, ultimately, achieving an FDA breakthrough [therapy] designation with a very high fidelity, with which we are able to transplant patients.2 We also have an orphan drug designation because [for] bone marrow transplantation, just under 9000 transplants are done every year in the United States.3 That puts us in the orphan drug status and that gives us a period of exclusivity for 12 years pending the [biologics license application; BLA] approval.
In additional, the FDA breakthrough status means that we are going to be strong candidates for a priority review and we have frequent interactions and significant advice from the FDA where we have been able to actually collaboratively design our phase 3 pivotal, global study, which was conducted at 33 sites in 4 continents.
Where we are is that we have completed the phase 3 study, we met our primary end point with a high degree of statistical significance. We have also met all of our secondary end points with statistical significance. As a result...we are doing some longer-term follow-up for safety and overall survival. We really have met all of the prespecified end points that we agreed to with the FDA. We are on track now to file a biologics license application by the end of this year.
The most difficult part of this is to qualify our 2 manufacturing sites. We then built our own Gamida Cell manufacturing site in Israel, which is going to account for more than 90% of the product output. We also have a second manufacturing source with Lonza in the Netherlands. We have been partners with Lonza throughout the entire clinical development, as they provided the majority of clinical batches for the bone marrow transplant trial. [However], for the commercial [manufacturing], we will take over the majority [of] the commercial transplants.
In cellular therapy, you really have to qualify, not just the process, the growth of the cells, and the specifications, but you have to qualify the site itself. [One has to] show analytical comparability and clinical comparability, such that phase 3 data [look] like the data in the commercial setting. In so doing, we have initiated an expanded access protocol, so even after completing the phase 3 trial, we have opened up sites that are continuing to treat patients. Firstly, [this is] because there is a continuous medical need for these patients; and secondly, we need to show that our commercial manufacturing sites will be adequate and suffice to be submitted with the BLA for pre-approval inspection by the FDA.