Multiple Myeloma Pipeline Insight
DelveInsight’s, “Multiple Myeloma (MM) – Pipeline Insight, 2020,” report provides comprehensive insights about 80+ companies and 120+ pipeline drugs in Multiple Myeloma pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.
Multiple Myeloma Understanding
Multiple Myeloma: Overview
Multiple Myeloma is the second most prevalent hematological malignancy worldwide, with a median onset of 60 years. This incurable malignancy develops from an accumulation of terminally differentiated monoclonal plasma cells (PC) in the bone marrow. In the United States, the lifetime risk for MM is 1 in 143 (0.7%). Multiple myeloma is a malignant disorder characterized by uncontrolled proliferation of clonal plasma cells causing a wide variety of complications leading to organ dysfunction and eventually death. Multiple myeloma is a malignant disorder characterized by uncontrolled proliferation of clonal plasma cells causing a wide variety of complications leading to organ dysfunction and eventually death.
Symptoms of Multiple Myeloma
Multiple myeloma is a rare, highly incurable malignant disease of plasma cells. Patients usually present with symptoms, such as:
- Renal insufficiency
- Lytic bony lesions along with a monoclonal protein in the serum and/or
- Increase in the number of clonal plasma cells in the bone marrow.
Almost all patients who have MM lately develop osteopenia or osteolytic lesions that result in pathologic fractures or severe bone pain. More than 50% of all patients who have MM develop pathologic fractures frequently resulting in severe debilitation.
Stages of Multiple Myeloma
For Durie–Salmon staging, each stage is sub-classified into A and B where; (A) normal renal function (serum creatinine <177 umol/L); (B) abnormal renal function (serum creatinne >177 umol/L). Some have an intermediate stage (smoldering or asymptomatic myeloma) which carries a transformation risk of 10% per year for the first 5 years, 3% per year for the next 5 years, and 1% per year for the subsequent 10 years (cumulative probability of 73% at 15 years). The median age at diagnosis is between 65 and 70 years. In 2005, the International Staging System (ISS) was validated using only β2-microglobulin and serum albumin as prognostic indicators. This is wildly accepted system as patients with ISS stage I have a median survival of 62 months; while those with stage III have 29 months.
Genetic and molecular biomarkers in the staging system can be both prognostic and predictive. At diagnosis, the presence of high-risk translocations and/or del (17p) confer poor survival outcome (4;14) predicts poor response to alkylating agents, therefore, treatment with a PI-based therapy is recommended. Similarly, a triplet combination of PI, IMiD, and glucocorticoid should be used for patients with del (17) at diagnosis, while at relapse, a third-generation IMiD and second or third-generation PI should be considered to overcome clonal resistance.
Treatment of Multiple Myeloma
There are several currently available treatment options for Relapsed/Refractory Multiple Myeloma. In addition to the approved newer myeloma agents (immunomodulatory agents [IMiDs] and PIs), combinations of cytotoxic agents and high-dose therapy with autologous stem cell transplant (HDT-SCT) have led to significant survival improvements seen currently. Chemotherapeutics which are mostly used for MM include Melphalan, Vincristine, Doxorubicin, and Liposomal doxorubicin. There are some medications, such as Bortezomib or the second-generation Carfilzomib that block the proteasome, leading to the accumulation of proteins in MM cells, causing their destruction. Immunomodulatory drugs modify the response of the immune system by increasing (immunostimulators) or decreasing (immunosuppressive) resulting in the production of serum antibodies. The introduction of the monoclonal antibodies Daratumumab (directed against CD38) and Elotuzumab (directed against SLAMF7) represents the latest wave of therapeutic advances in the treatment of multiple myeloma and other plasma cell disorders. Adjunctive supportive care is very important in patients with MM and includes measures to treat complications of the disease and to prevent the morbidities associated with the disease and its treatment.
Multiple Myeloma Emerging Drugs Chapters
This segment of the Multiple Myeloma report encloses its detailed analysis of various drugs in different stages of clinical development, including BLA Filed, Phase III, II, I and Pre-clinical. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases.
Multiple Myeloma Emerging Drugs
- Idecabtagene vicleucel: Bristol-Myers Squibb/Bluebird bio
Idecabtagene vicleucel (ide-cel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T cell immunotherapy in development (Phase III) for the treatment of adult patients with multiple myeloma who have received at least three prior therapies. The ide-cel CAR is comprised of a murine extracellular single-chain variable fragment (scFv) specific for recognizing BCMA, attached to a human CD8 α hinge and transmembrane domain fused to the T cell cytoplasmic signaling domains of CD137 4-1BB and CD3-ζ chain, in tandem. It recognizes and binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.
- Belantamab mafodotin (GSK2857916): GlaxoSmithKline
Belantamab mafodotin (GSK2857916, Phase III) is a first-in-class, anti-BCMA immunoconjugate with an afucosylated, humanized IgG1 anti-BCMA monoclonal antibody conjugated by a protease-resistant maleimidocaproyl linker to a microtubule-disrupting agent, monomethyl auristatin F (MMAF).
Belantamab mafodotin binds to BCMA and kills multiple myeloma cells via a multimodal mechanism, including delivery of MMAF to BCMA-expressing multiple myeloma cells, thereby inducing apoptosis; enhancing antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis; and inducing immunogenic cell death.
- LCAR-B38M: Janssen Biotech/Nanjing Legend Biotech
Atezolizumab (Tecentriq, Phase III) is a novel, anti-PDL1 targeted prescription cancer immunotherapy. It is monoclonal antibody derived from the Chinese hamster ovary cells by recombinant DNA technology. Atezolizumab works by binding to PD-L1 receptor expressed on tumor cells and tumor-inﬁltrating immune cells and thereby leads to the prevention of binding of PD-L1 receptor to other proteins namely as B7.1 and PD-1. This process leads to the release of PD-1/ PD-L1 mediated inhibition of the immune response, and also causes the activation of anti-tumor immune response without inducing the antibody dependent cellular cytotoxicity (ADCC).
- Melphalan flufenamide: Oncopeptides
Melflufen is a first-in-class anti-cancer peptide-drug conjugate that rapidly delivers an alkylating payload into tumor cells. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and is immediately cleaved by peptidases to deliver an entrapped hydrophilic alkylator payload. Melflufen is an investigational drug (Phase III) and is not approved for commercial use.
Venclexta (venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. It targets the BCL-2 protein and works to help restore the process of apoptosis. It is being developed by AbbVie and Roche.
- TJ202: I-Mab Biopharma/ MorphoSys
TJ202 (Phase III) was originally developed by MorphoSys and showed favorable clinical safety and efficacy data from a clinical trial conducted in the European Union (EU). I-Mab Biopharma own an exclusive license right to develop TJ202 in Greater China to address the current unmet needs and commercial opportunities in China for multiple myeloma and potentially autoimmune diseases, such as systemic lupus erythematosus (SLE).
BL-8040 is a short synthetic peptide for stem cell mobilization and for treatment of hematological malignancies and solid tumors. It functions as a high-affinity best-in-class antagonist for CXCR4, a chemokine receptor that is directly involved in the retention of stems cells in the bone marrow, as well as tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity.
Further product details are provided in the report…
Multiple Myeloma: Therapeutic Assessment
This segment of the report provides insights about the different Multiple Myeloma drugs segregated based on following parameters that define the scope of the report, such as:
- Major Players in Multiple Myeloma
There are approx. 80+ key companies which are developing the therapies for Multiple Myeloma. The companies which have their Multiple Myeloma drug candidates in the most advanced stage, i.e. BLA Filed include, Bristol-Myers Squibb/Bluebird bio and GlaxoSmithKline.
DelveInsight’s report covers around 120+ products under different phases of clinical development like
- Late stage products (BLA Filed and Phase III)
- Mid-stage products (Phase II and Phase I/II) and
- Early-stage products (Phase I) along with the details of
- Pre-clinical and Discovery stage candidates
- Discontinued & Inactive candidates
- Route of Administration
Multiple Myeloma pipeline report provides the therapeutic assessment of the pipeline drugs by the Route of Administration. Products have been categorized under various ROAs such as
- Intravenous and Oral
- Intravenous and Subcutaneous
- Subcutaneous etc.
- Mechanism of Action
- Products have been categorized under various MOAs such as
- B cell maturation antigen Antagonist
- T lymphocyte replacements
- Angiogenesis inhibitors
- Apoptosis stimulants
- DNA synthesis inhibitors
- Proto-oncogene protein c-bcl-2 inhibitors
- CXCR4 receptor antagonists
- Programmed cell death-1 ligand-1 inhibitors
- Cereblon modulating agents
- Proto oncogene protein b raf inhibitors
- Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)
- Antibody-dependent cell cytotoxicity
- CD34 antigen stimulants
- Cytotoxic T lymphocyte stimulants
- XPO1-mediated nuclear export (SINE) inhibitor
- CD38 antigen modulators
- Anti-CD38 Monoclonal antibody
- Fibroblast growth factor receptor (FGFR) types 1, 2, and 3 (FGFR1/2/3) antagonists
- Proteasome inhibitors
- Dopamine receptor D2 (DRD2) and mitochondrial caseinolytic protease P (ClpP) agonist
- Vascular endothelial growth factor A inhibitors; Hepatocyte growth factor inhibitors
- Mitogen-activated protein kinase inhibitors
- CRBN protein modulators
- P300-CBP transcription factor inhibitor
- Bruton tyrosine kinase inhibitor
- MCL1 inhibitor
- Arginase inhibitors
- Cyclin dependent kinase 9 inhibitors
Products have been categorized under various Molecule types such as
- Small molecules
- Antibody drug conjugate
- CAR-T cell therapies
- Peptide-drug conjugate
- CD38 monoclonal antibody
- Natural killer cell therapies
- Gene therapy
- Peptide vaccines
- BCMAxCD3 bispecific antibody
- Anti-CD38 Monoclonal antibody
- T-Lymphocyte replacements
- Trispecific antibodies
- Product Type
Drugs have been categorized under various product types like Mono, Combination and Mono/Combination.
Multiple Myeloma: Pipeline Development Activities
The report provides insights into different therapeutic candidates in phase III, II, I and preclinical stage. It also analyses Multiple Myeloma therapeutic drugs key players involved in developing key drugs.
Pipeline Development Activities
The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Multiple Myeloma drugs.
- The companies and academics are working to assess challenges and seek opportunities that could influence Multiple Myeloma R&D. The therapies under development are focused on novel approaches to treat/improve Multiple Myeloma.
- In January 2020, GlaxoSmithKline announced the US Food and Drug Administration granted a priority review for the company’s Biologics License Application (BLA) seeking approval of belantamab mafodotin (GSK2857916) for the treatment of patients with relapsed or refractory multiple myeloma whose prior therapy included an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.
- In October 2019, I-Mab Biopharma and MorphoSys announced that I-Mab has received Investigational New Drug (IND) clearances from the National Medical Products Administration (NMPA) of China to expand the ongoing phase II and III clinical trials of TJ202/MOR202, MorphoSys's human monoclonal anti-CD38 antibody for the treatment of multiple myeloma, also to mainland China.
- In November 2019, Bristol-Myers Squibb completed the acquisition of Celgene.
- In November 2017, bb2121 was granted Breakthrough Therapy Designation (BTD) by the US FDA for the treatment of patients with Relapsed and Refractory Multiple Myeloma.
- In the very same year, bb2121 was granted PRIority MEdicines (PRIME) eligibility by the European Medicines Agency (EMA) for the treatment of patients with Relapsed and Refractory Multiple Myeloma.
- In March 2018, Bluebird Bio and Celgene Corporation announced that the companies have entered into an agreement to co-develop and co-promote bb2121, an investigational anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy for the potential treatment of patients with relapsed/refractory multiple myeloma in the United States.
- In December 2017, Janssen Biotech entered into a worldwide collaboration and license agreement with Legend Biotech USA Inc. and Legend Biotech Ireland Limited (“Legend”), subsidiaries of Genscript Biotech Corporation, to develop, manufacture and commercialize a chimeric antigen receptor (CAR) T-cell drug candidate, LCAR-B38M.
- The ECT-001 technology is a combination of a small molecule, UM171, and an optimized culture system. The technology, capable of expanding the number of stem and immune cells exponentially in as little as seven days, is used in novel curative cord blood transplant therapies for patients with blood cancers, allowing more rapid engraftment, greatly reduced incidence of transplant-related mortality, low risk of chronic graft-versus-host disease and low risk of relapse, resulting in better outcomes for patients.
- With its proprietary TriTAC format (Tri-specific T Cell-Activating Construct), Harpoon is taking this modality to the next level. This novel class of T cell therapeutics aims to achieve superior efficacy in penetrating solid tumors as an “off-the-shelf” T cell therapy. TriTACs, which are comprised of three binding domains, are designed to have an extended serum half-life and be about one-third the size of a monoclonal antibody.
Multiple Myeloma Report Insights
- Multiple Myeloma Pipeline Analysis
- Therapeutic Assessment
- Unmet Needs
- Impact of Drugs
Multiple Myeloma Report Assessment
- Pipeline Product Profiles
- Therapeutic Assessment
- Pipeline Assessment
- Inactive drugs assessment
- Unmet Needs
Current Treatment Scenario and Emerging Therapies:
- How many companies are developing Multiple Myeloma drugs?
- How many Multiple Myeloma drugs are developed by each company?
- How many emerging drugs are in mid-stage, and late-stage of development for the treatment of Multiple Myeloma?
- What are the key collaborations (Industry–Industry, Industry–Academia), Mergers and acquisitions, licensing activities related to the Multiple Myeloma therapeutics?
- What are the recent trends, drug types and novel technologies developed to overcome the limitation of existing therapies?
- What are the clinical studies going on for Multiple Myeloma and their status?
- What are the key designations that have been granted to the emerging drugs?