Advancing Care for Hematologic Malignancies: Chris Heery from Arcellx in a Stimulating Dialogue Exchange with PharmaShots

Shots:

Arcellx’s Anito-cel, a BCMA CAR-T therapy recently got the FTD, ODD, RMAT designations by the FDA for the treatment of patients with relapsed or refractory multiple myeloma (r/rMM)

Today, at PharmaShots we have Chris Heery, Chief Medical Officer at Arcellx, shedding light on Anito-Cel therapy in advancing care for multiple myeloma

In late 2022, Arcellx signed a collaboration agreement with Kite Pharma (Gilead Science) to co-develop and co-commercialize anito-cel for patients with r/rMM

Saurabh: Congratulations on anito-cel getting Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the FDA. Could you tell us more about anito-cel? 

Chris: Anito-cel is an autologous CAR-T therapy derived from our synthetic binder, the D-Domain. We believe the D-Domain differentiates our CAR-T therapy and will allow us to excel at the four core drivers of market adoption in the CAR-T space: efficacy, safety, scale, and reliable manufacturability. You may also be interested to know that we have a late-stage pivotal clinical trial underway to treat patients with relapsed or refractory multiple myeloma (rrMM). In a Phase 1 clinical trial in rrMM, anito-cel demonstrated deep and durable responses in patients with poor prognostic factors and a manageable safety profile. Specifically, 76% of patients achieved a complete response and the duration of responses was over two years.

Saurabh: Can we briefly talk about the present treatment options in the MM space with special focus on CGTs? Standard of Care recommended by NCCN, ESMO.

Chris: In patients with multiple myeloma, standard of care is to start treatment with a combination of at least two of the three “backbone” classes of drugs. These are called IMiDs, proteasome inhibitors, and anti-CD38 antibodies. The combination of two or three of these classes of drugs is always given with a third drug class, a potent steroid.

With first-line treatment, which may or may not include a stem cell transplant using the patient’s previously stored stem cells (called an autologous stem cell transplant), it is common to see treatment result in five or more years of disease control.

After the disease progresses with first-line therapy, other drug combinations, often using different drugs from the three classes, are used. Second-line therapy will have varying duration of disease control depending on the agents used in first line and other prognostic features in each patient’s case.

After the three main classes of drugs can no longer provide benefit, approved options include CAR-T cell therapy and bispecific T cell engagers. CAR-T cell therapies that have been approved are called cilta-cel and ide-cel. Recently, cilta-cel was approved for use in second-line therapy and ide-cel was approved for use in third line.

We believe there is still a supply constraint on CAR-T cell therapies for all patients who could benefit from their use. This constraint exists in later lines, such as fourth-line therapy, but it is even more significant in earlier lines, like second-line therapy.

Saurabh: What are the unmet needs of the presently available treatment options which anito-cel can address? 

Chris: We believe the current unmet need for treating patients with relapsed or refractory multiple myeloma (rrMM) with CAR-T therapy centers around durability, safety, and manufacturing. At ASH 2023, Arcellx presented interim anito-cel data from its Phase 1 expansion clinical trial that demonstrated deep and durable responses in patients with poor prognostic factors and continued to be well tolerated at the time of the October 15, 2023, data cut with no delayed neurotoxicity events or parkinsonian symptoms being observed. We believe this profile combination of safety and efficacy is unique and may fit well into the expectations for clinicians and patients.

Additionally, in December 2022, Arcellx and Kite Pharma, a Gilead Company, announced a strategic collaboration to co-develop and co-commercialize anito-cel for patients with rrMM. Kite is the global leader in CAR-T manufacturing. Leveraging Kite’s large commercial footprint and manufacturing expertise, we believe anito-cel is well positioned for launch and scale.

Saurabh: Shed some light on the specialized treatment approaches by Arcellx for multiple myeloma patients.

Chris: In our upcoming Phase 3 trial, which is called iMMagine-3, we have selected a patient population that we believe is very common now and will grow in size over the next five to 10 years. Instead of requiring that a patient must meet specific criteria demonstrating their disease to be refractory to prior therapy, we are studying anito-cel in patients that must have only had exposure to proteasome inhibitors and anti-CD38 antibodies. We believe these criteria will provide more insight into the real-world use case for anito-cel in second line and later therapy.

Additionally, we are evaluating clinical trial designs for front-line therapy with anito-cel, in collaboration with our partners at Kite.

Saurabh: Could you tell us about the immune cells' potential for the treatment of patients with relapsed/refractory multiple myeloma? 

Chris: CAR-T cells appear to be the most efficient killers of target cells currently available in cancer care.

Specifically for patients with relapsed or refractory multiple myeloma, no other therapy can offer the promise of a one-time treatment that can have a duration of benefit that extends well over two years in most patients.

We believe that this durability of benefit should increase the quality of life for patients due to the extended treatment-free interval. We are confident that most patients would prefer a therapy that allows them more freedom from repeated treatment and doctor visits.

Saurabh: What are the other indications beyond MM, Arcellx plans to assess anito-cel? 

Chris: Arcellx is also developing anito-cel for treating generalized myasthenia gravis (gMG), an autoimmune disease. Additional plasma cell-related indications outside of cancer are being considered, but we have not yet disclosed the plans for those indications.

Saurabh: What other countries are you planning to launch anito-cel, except the U.S.?

Chris: As part of our collaboration with Kite, Kite will commercialize anito-cel outside the U.S., including Europe and other geographies. Arcellx will receive low to mid-teen royalties on sales.

Image Source: Canva

About the Author:

Chris Heery

Chris has served as Arcellx's Chief Medical Officer since April 2021. Prior to that, he served as Chief Medical Officer of Precision BioSciences and Bavarian Nordic. At Precision, he oversaw the clinical development of one of the first allogeneic CAR-T cell platforms and provided clinical insight into clinical efforts for gene editing therapeutics. While at Bavarian Nordic, he oversaw clinical development programs for its immune-oncology and infectious disease vaccine portfolio. Prior to his roles in biotech, he was head of the Clinical Trials Group of the Laboratory of Tumor Immunology and Biology at the National Cancer Institute (NCI). He joined NCI Medical Oncology Branch as a Medical Oncology Fellow in 2009 and held an Adjunct Appointment in the Genitourinary Malignancies Branch. At NCI, Dr. Heery was part of the larger effort of the Laboratory of Tumor Immunology and Biology to create new immunotherapies for the treatment of cancer. Dr. Heery is board- certified in Medical Oncology and Internal Medicine and completed his internal medicine residency at the University of Illinois at Chicago after receiving his MD from East Carolina University Brody School of Medicine. Dr. Heery also holds a BA in English Literature from Duke University.