The "Cytokine Release Syndrome (CRS)-Market Insights, Epidemiology, and Market Forecast-2030" drug pipelines has been added to ResearchAndMarkets.com's offering.
This report delivers an in-depth understanding of the Cytokine Release Syndrome (CRS), historical and forecasted epidemiology as well as the Cytokine Release Syndrome (CRS) market trends in the United States, EU5 (Germany, France, Italy, Spain, and United Kingdom) and Japan.
The report provides current treatment practices, emerging drugs, and market share of the individual therapies, current and forecasted 7MM Cytokine Release Syndrome (CRS) market size from 2017 to 2030. The report also covers current Cytokine Release Syndrome (CRS) treatment practice/algorithm, market drivers, market barriers and unmet medical needs to curate the best of the opportunities and assesses the underlying potential of the market.
The disease epidemiology covered in the report provides historical as well as forecasted epidemiology segmented by Total Number of B-cell NHL Patients receiving CART-Therapies, Total Number of Acute lymphoblastic leukemia (ALL) Patients receiving CART-Therapies, Total Number of Multiple Myeloma (MM) Patients receiving CART-Therapies, Total Number of Patients developing Cytokine Release Syndrome (CRS) following CART therapies, and Total Number of Patients Developing Cytokine Release Syndrome (CRS) by Severity/Grade, scenario of CRS in the 7MM covering the United States, EU5 countries (Germany, France, Italy, Spain, and United Kingdom) and Japan from 2017 to 2030.
- Total number of patients who develop Cytokine Release Syndrome following CART therapies in the 7MM were 31 in 2017.
- Total number of Hematologic malignancies (Includes ALL, B-Cell NHL (DLBCL, FL, PMBCL, etc.), and Multiple Myeloma) patients receiving CART-therapies in the 7MM were observed to be 41 in 2017. These cases will increase in the 7MM throughout the study period, i.e., 2017-2030.
- Both the therapies Yescarta (Axicabtagene ciloleucel, Kite/Gilead) and Kymriah (Tisagenlecleucel, Novartis) were approved in 2017 in the United States and 2018 in EU-5. Kymriah is the only CAR-T cell therapy, which was approved in Japan in 2019
- Among the European 5 countries, Germany had the highest population of CRS with 13 cases, followed by France and the United Kingdom with 11 cases respectively. On the other hand, Spain had the lowest population of 6 cases in 2018.
- Based on the severity criteria, CRS has been classified into Grade 1, 2, 3, and 4. Out of the total population of CRS 31 cases in the US, the highest cases were observed in the grade 1 & 2, and lowest cases accounted in grade 4 in 2017.
- There is no CAR-T therapy which is approved for Multiple Myeloma (MM) patients. According to the publisher, there are around 6-8 emerging CAR-T cell therapies which are expected to launch during forecast period for the treatment of MM and patients will experience cytokine release syndrome. As comparison to Yescarta (Axicabtagene ciloleucel, Kite/Gilead) and Kymriah (Tisagenlecleucel, Novartis), new CAR-T cell therapies that are going to be approved in forecast period, will show lower incidence of Cytokine Release Syndrome based on the preliminary results.
The drug chapter segment of the Cytokine Release Syndrome (CRS) report encloses the detailed analysis of CRS marketed drugs, mid-phase, and late-stage pipeline drugs. It also helps to understand the Cytokine Release Syndrome (CRS) clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details of each included drug and the latest news and press releases.
Actemra/RoActemra (tocilizumab): Genentech
Actemra (tocilizumab) is the first drug approved for the treatment of chimeric antigen receptor (CAR) T-cell-induced severe or life-threatening CRS in patients 2 years and older. Apart from being used in the treatment of chimeric antigen receptor (CAR) T-cell-induced severe or life-threatening cytokine release syndrome (CRS) in adults and pediatric patients 2 years and older, the drug is also approved to treat adults with moderately to severely active rheumatoid arthritis (RA), adults with giant cell arteritis (GCA), and children ages two and above with Polyarticular Juvenile Idiopathic Arthritis (PJIA) or Systemic Juvenile Idiopathic Arthritis (SJIA). The drug is approved under the name Actemra in the US and Japan, and as RoActemra in Europe.
Itacitinib: Incyte Corporation
Itacitinib is a potent orally bioavailable and highly selective inhibitor of Janus kinase (JAK)-1, which mediates signaling of several inflammatory cytokines. In preclinical studies of CRS models, JAK1 inhibition with ITA significantly reduced serum levels of cytokines implicated in CRS, including IL-6, IL-12, and IFN-, without affecting the antitumor activity of human CD19 CAR T-cells in vivo, suggesting potential utility in the management of CRS.
Defitelio (Defibrotide): Jazz Pharmaceuticals
Defibrotide, sold under the brand name Defitelio, is a mixture of single-stranded oligonucleotides that is purified from the intestinal mucosa of pigs. Currently, the company is conducting a Phase II clinical trial to evaluate defibrotide intravenous infusion in the prevention of cytokine release syndrome.
Anakinra: Kite Pharma/Swedish Orphan Biovitrum (Sobi)
Anakinra is a recombinant human interleukin-1 (IL-1) receptor antagonist protein. It is administered through the subcutaneous route and approved for the treatment of rheumatoid arthritis and cryopyrin-associated periodic syndromes (CAPS). Company is developing anakinra in axicabtagene ciloleucel therapy to reduce the occurrence of the side effects - cytokine release syndrome (CRS) - and neurologic toxicities with relapsed or refractory Non-Hodgkin lymphoma (NHL). The company is investigating this combination in phase II clinical trial. Another Phase II clinical trial is conducted by Swedish Orphan Biovitrum (Sobi) in collaboration with Fred Hutchinson Cancer Research Center and National Cancer Institute (NCI) to investigate the potential of anakinra in axicabtagene ciloleucel therapy in reducing CRS and neurotoxicity in patients with B-cell lymphoma who are receiving CD19-targeted CAR T-cell therapy.
IL-6 has emerged as a critical cytokine in exacerbating the progression of CRS in T-cell-engaging therapies. Depending on the clinical center, both tocilizumab (IL-6 receptor targeting monoclonal antibody) and siltuximab (chimeric anti-IL-6 monoclonal antibody) have been used as approaches to control CRS. In light of the approval of Actemra (tocilizumab) for management of CRS by both US FDA and European Medicines Agency, there have been concerns raised about the possible elevation of IL-6 due to blockade of the receptor that subsequently leads to accumulation of this effector cytokine in the CNS.
Subsequent studies confirmed that the administration of monoclonal antibodies against IL-6 (siltuximab) and its receptor (tocilizumab) led to the rapid resolution of CRS symptoms. In an early-stage clinical trial, tocilizumab demonstrated a 69% response rate in patients with severe or life-threatening CRS. As a consequence, tocilizumab has quickly become the gold standard for the initial treatment of severe CRS in patients receiving CAR T-cells.
Currently, there are several other IL-6-targeting monoclonal antibodies in late-stage clinical development, which could also potentially be used to treat CRS. Siltuximab is a chimeric, IG monoclonal antibody that binds human IL-6 and prevents it from interacting with both the membrane-bound and soluble form of the IL-6 receptor. Clazakizumab is another monoclonal antibody targeting IL-6. Corticosteroids should generally be avoided as first-line treatment of CRS in patients receiving CAR T-cells and should be reserved for cases refractory to IL-6 blockade or patients with severe neurotoxicity. The current recommendations, therefore, prefer the use of corticosteroids for the treatment of the neurologic adverse effects of T-cell engaging therapies.
Monoclonal antibodies target IL-6 directly, thereby eliminating it from the circulation, which might be advantageous in patients with severe CRS and concurrent neurotoxicity since tocilizumab does not cross the blood-brain barrier, and therefore, fails to inhibit IL-6 signaling in the CNS. Corticosteroids should also be considered in patients who develop HLHI/MAS as part of their CRS.
- The market size of Cytokine Release Syndrome (CRS) in the 7MM was found to be USD 0.16 million in 2017.
- Among the 7MM countries, the United States had the highest market size of Cytokine Release Syndrome (CRS) in 2019, which accounts for approximately 85.46% of the total market.
This section focuses on the rate of uptake of the potential drugs recently launched in the Cytokine Release Syndrome (CRS) market or expected to get launched in the market during the study period 2017-2030. The analysis covers Cytokine Release Syndrome (CRS) market uptake by drugs; patient uptake by therapies; and sales of each drug.
This helps in understanding the drugs with the most rapid uptake, reasons behind the maximal use of new drugs and allows the comparison of the drugs based on market share and size which again will be useful in investigating factors important in market uptake and in making financial and regulatory decisions.
The report provides insights into different therapeutic candidates in phase II, and phase III stage. It also analyzes key players involved in developing targeted therapeutics.
Pipeline Development Activities
The report covers the detailed information of collaborations, acquisition, and merger, licensing and patent details for Cytokine Release Syndrome (CRS) emerging therapies.
Reimbursement is a crucial factor that affects the drug's access to the market. Often, the decision to reimburse comes down to the price of the drug relative to the benefit it produces in treated patients.
Tocilizumab is a recombinant humanized anti-human IgG1 monoclonal antibody directed against the interleukin-6 receptor (IL-6R) that binds specifically to both soluble and membrane-bound IL-I receptor (L-6R), thereby inhibiting IL-6-mediated signaling. IL-6 is a cytokine produced by a wide variety of cells in the human body. Its normal role is primarily to regulate hematopoiesis, to stimulate immune responses, and to mediate acute phase reactions (CHMP, 2018b).
Medicare does not have a National Coverage Determination (NCD) that addresses Actemra (tocilizumab) explicitly. NCD is an evidence-based determination of whether Medicare will pay for an item or service. Also, Local Coverage Determinations (LCDs) do not exist for Actemra (UnitedHealthcare, 2020).
Genentech is running an Actemra Co-pay Card Program that helps eligible commercially insured patients to pay as low as USD 5 for the drug. The card has validity for up to USD 15,000 of co-pay assistance within 12 months (Genentech, 2020). It also helps patients by referring to the Medicare Low-Income Subsidy (LIS) program for patients with Medicare Part D. It refers to patients without insurance, medical coverage, or high out of pocket costs to Genentech Patient Foundation. The foundation may help the patient with free medication.
Competitive Intelligence Analysis
The publisher performs competitive and market Intelligence analysis of the Cytokine Release Syndrome (CRS) market by using various competitive intelligence tools that include-SWOT analysis, PESTLE analysis, Porter's five forces, BCG Matrix, Market entry strategies, etc. The inclusion of the analysis entirely depends upon the data availability.
- Novartis Pharmaceuticals
- Incyte Corporation
- Jazz Pharmaceuticals
- Swedish Orphan Biovitrum (Sobi)
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