FDA Approves Tecelra, First T Cell Therapy for Solid Tumors

On August 2, 2024, the FDA granted accelerated approval for Tecelra (afamitresgene autoleucel) a melanoma-associated antigen A4 (MAGE-A4)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, 16 -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices. Tecelra is contra-indicated in adults who are heterozygous or 52 homozygous for HLA-A*02:05P.[i]

Synovial sarcoma is an uncommon and aggressive cancer that can form in soft tissues such as muscles, fat, joint linings, and ligaments. It is often found in the arm, leg, or foot, and near joints such as the wrist or ankle. It can also form in soft tissues in the lung or abdomen. Although synovial sarcoma can affect people at any age, it is known to occur more commonly in adolescents and adults younger than 30.[ii] Adults with metastatic synovial sarcoma at diagnosis have a 5-year overall survival rate of 10%, versus 76% for those with localized disease at diagnosis.[iii]

Synovial sarcoma (SS) accounts for up to 10% of all soft-tissue sarcomas. In the US, 800-1000 new cases of SS are diagnosed annually. According to an analysis of the Surveillance, Epidemiology, and End Results (SEER) database study, the age-adjusted incidence rate of SS in the US is 0.177 per 100,000 (approximately 580 incident cases) with a prevalence rate of 0.65 per 100,000 (approximately 2129 prevalent cases).[iv]

Tecelra is an autologous T cell immunotherapy composed of a patient’s own T cells. T cells in Tecelra are modified to express a TCR that targets MAGE-A4 expressed by cancer cells in synovial sarcoma. After the patient undergoes leukapheresis, cells are sent for manufacturing. It takes about six weeks for the Tecelra to be returned to the provider, though that time may vary.

The patient is admitted to the hospital and receives a lymphodepleting chemotherapy regimen of fludarabine 30 mg/m2/day intravenously for four days starting on the seventh day before Tecelra infusion (Day-7 to Day -4), and cyclophosphamide 600 mg/m2/day intravenously for 3 days starting the seventh day before Tecelra infusion (Day -7 to Day -5).  Tecelra is administered over an hour as a single intravenous infusion on Day 1.  The patient will remain hospitalized for at least seven days after the infusion. The patient should plan to stay close to a healthcare facility for at least four weeks.[v]

The safety and effectiveness of Tecelra were evaluated in a multicenter, open-label clinical trial. Effectiveness was evaluated based on overall response rate and the duration of response to treatment with Tecelra. Among the 44 patients in the trial who received Tecelra, the overall response rate was 43.2% and the median duration of response was six months. Tecelra was approved under an accelerated approval pathway and a confirmatory trial is ongoing to verify Tecelra’s clinical benefit.[vi]

A Black Box Warning has been issued because patients may experience cytokine release syndrome. Patients may also exhibit Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS).

The current list price for  Tecelra is $727,000. This does not include the pre-treatment or hospitalization costs associated with the administration of the therapy.

Article by Kathy Clark, RN, BSN, CMCN, Vice President, Director of Managed Care. For more information about how this may affect your plan, please contact your Summit ReSources care specialist. The following sources were used as reference material for this article:

[i] FDA Package Insert-Tecelra. https://www.fda.gov/media/180565/download?attachment. Accessed 8/12/2024.

[ii] National Cancer Institute. Synovial Sarcoma. https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-soft-tissue-tumors/synovial-sarcoma#:~:text=Synovial%20sarcoma%20is%20a%20cancer,also%20be%20called%20malignant%20synovioma. Accessed 8/12/2024.

[iii]Blay JY, von Mehren M, Jones RL, Martin-Broto J, Stacchiotti S, Bauer S, Gelderblom H, Orbach D, Hindi N, Dei Tos A, Nathenson M. Synovial sarcoma: characteristics, challenges, and evolving therapeutic strategies. ESMO Open. 2023 Oct;8(5):101618. doi: 10.1016/j.esmoop.2023.101618. Epub 2023 Aug 23. PMID: 37625194; PMCID: PMC10470271. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470271/ Accessed 8/12/2024.

[iv] Mangla A, Gasalberti DP. Synovial Cell Sarcoma. [Updated 2023 May 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK587366/. Accessed  8/12/2024.

[v] FDA Package Insert-Tecelra. https://www.fda.gov/media/180565/download?attachment. Accessed 8/12/2024.

[vi] FDA. FDA Approves First Gene Therapy to Treat Adults with Metastatic Synovial Sarcoma. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-metastatic-synovial-sarcoma. Accessed 8/12/2024.

GLP-1 Drugs: Where We Are and Where We’re Going

While health plans struggle with coverage questions and the high cost of GLP-1 (glucagon-like peptide-1) drugs, there is no doubt they are not going away. These drugs have caused a revolution in the diabetes and weight loss arenas not only due to their success, but also because of their cost. With many more clinical trials underway to determine if these drugs will be useful in treatment of other diseases, plans should prepare for possible expanded indications in the future and begin to discuss how their coverage decisions may look.

The four most visible and discussed drugs are:

• Ozempic, which is semaglutide and approved for type 2 diabetes. Manufactured by Novo Nordisk.

• Wegovy, which is also semaglutide but approved for weight loss. Manufactured by Novo Nordisk.

• Mounjaro, which is tirzepatide and approved for type 2 diabetes. Manufactured by Eli Lilly.

• Zepbound, also tirzepatide, approved for weight loss. Manufactured by Eli Lilly.

There is a difference between Ozpempic/Wegovy and Mounjaro/Zepbound. Monjouro/Zepbound is a GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 receptor agonist. Whereas Ozempic and Wegovy are GLP-1 receptor agonists only. They do work in similar ways given both have GLP-1 receptor agonist properties. GLP-1s mimic a hormone produced in the gut to suppress a person’s appetite and regulate blood sugar.

Currently, approximately 80% of plans cover these drugs for type 2 diabetes. Coverage is far less ubiquitous for obesity and weight loss. List price is in the $1000-1300 per month range, with actual net price being lower due to rebates and savings/coupons from the manufacturers. Lilly offers a savings card for those with commercial insurance that does not cover Zepbound. It lists savings up to $563/month, reducing the cost per month to $550.

We are now seeing many more research studies for other indications and treatment with these drugs. Ozempic and Wegovy have recently gained FDA approval for patients with type 2 diabetes and known cardiovascular disease, as well as for adults with established cardiovascular disease and obesity or overweight. These patients are at a greater risk of major cardiovascular events such as stroke, heart attack, or death. Ozempic and Wegovy are proven to significantly lower those risks. Medicare is now paying for these drugs in certain cases, which is new as Medicare has previously been forbidden by law to cover weight loss drugs.

Tirzepatide, the active ingredient in Mounjaro and Zepbound, is now being studied for treatment of kidney disease. Another clinical trial is in progress for Zepbound and its impact on cardiovascular disease. Lilly is anticipating the results of that study in 2025, potentially expanding its labeled indications.

Furthermore, Zepbound is being studied for sleep apnea and, with FDA Fast Track designation, results are expected to be submitted to the FDA midyear 2024. In a Phase 3 study, people on CPAP had a reduction in the average hourly number of apnea episodes by up to 30 (63%) compared with an average reduction of 6 for those who received a placebo. Lilly is also studying Zepbound for treatment of MASH (metabolic associated steatohepatitis) and has met its goal in a Phase 2 study. MASH is a leading cause of liver transplantation.

With the US in the midst of an opioid epidemic in which it is estimated that one person dies of an overdose every five minutes, Penn State College of Medicine is among the first to investigate the potential of GLP-1 drugs for the treatment of addiction. Early results from a small clinical trial look promising and they plan to begin a larger clinical trial later this year of GLP-1 drugs to treat opioid addiction in the outpatient setting.

A recently published retrospective cohort study published in JAMA Network Open on July 5, 2024, noted a decrease in eleven obesity-associated cancers (OACs) in patients taking GLP-1 medications. According to the Centers for Disease Control (CDC), there are thirteen OACs: adenocarcinoma of the esophagus, post-menopausal breast cancer, colorectal cancer, uterine cancer, gallbladder cancer, upper stomach cancer, kidney cancer, ovarian cancer, pancreatic cancer, thyroid cancer, meningioma, and multiple myeloma. GLP-1 drugs were associated with a lower incidence of ten OACs compared to insulin. The study revealed that type 2 diabetes patients prescribed GLP-1 drugs were 65% less likely to get gallbladder cancer and 63% less likely to get meningioma than those prescribed insulin.

Additionally, the risk of pancreatic cancer was 59% lower, and the risk of hepatocellular carcinoma was 53% lower. Other cancers, including ovarian, colorectal, esophageal, endometrial, and kidney, were 48%, 46%, 40%, 36%, and 34% lower, respectively. The risk of multiple myeloma was 41% lower in those taking GLP-1 drugs compared to insulin.

Both Lilly and Novo Nordisk are testing pill forms of these drugs (currently they are given once weekly by subcutaneous injection). This would be appealing to many more people but historically it has been difficult for the body to absorb medication through the gastrointestinal tract. Several other manufacturers have clinical trials in progress for potential competitors. Many of these trials will end with data expected late 2024 and into 2025.

The success of these drugs as a non-invasive treatment for obesity has led to an estimated decrease of 15% in bariatric surgeries. In addition, peripheral businesses are now expanding to serve patients taking these medications. These services include areas such as nutrition coaching, dieticians, behavioral modification, exercise programs, and data collection and analytics to track it all.

Finally, the staggering costs of these popular drugs has come sharply into focus, with US Senator Bernie Sanders leading the charge. In an April 2024 letter to Novo Nordisk, the senator notes that while Novo Nordisk charges $1,349 a month for Wegovy in the US, the drug costs just $187 a month in Denmark, $137 a month in Germany and $92 a month in the UK. Ozempic costs $969 a month in the US compared to just $155 a month in Canada and $59 a month in Germany.

Novo Nordisk’s response suggested that those figures did not take into account the resources spent in the years of research and development, stating it spent $10 billion on development of GLP-1 drugs. Novo Nordisk also stated that it retains 60% of the cost and the other 40% goes to “middlemen” in the complex US health system. The CEO has agreed to testify before the Senate Committee on Health, Education, Labor and Pensions in September 2024.

Looking toward the future, one has only to look at www.ClincalTrials.gov to see the many studies underway and planned for these drugs. Conditions to be studied include the following:

Not only are these drugs are not going away, but there are also several new products in the pipeline. And as indicated by the list above of upcoming trials, there may be several new indications in the near future. Will the upfront cost prevent more serious and ongoing treatment in the future? The answer is yet unclear, but questions like this continue to loom larger. Each plan must review the possibilities and responsibilities it has to its members and organizations in order to make appropriate decisions about coverage.

Article written by Ginny Fisher, RN, BSN, CCM, Managed Care Specialist for Summit Reinsurance Services, Inc. For more information about how this may affect your plan, please contact your Summit ReSources care specialist. The following sources were used as reference material for this article:

• Biopharma Dive.com

• JAMA Network Open

• Penn State Health News

• Pharmanewsintel.com

• Morningstar

• Sanders.senate.gov