Multiple Myeloma Disease Coverage Forecast and Market Analysis
Author: David Dahan
Publisher: Datamonitor Healthcare
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DISEASE OVERVIEW
Multiple myeloma is characterized by the infiltration of malignant, antibody-producing plasma cells in the bone marrow. Almost all cases occur in individuals aged over 40 years, and age at diagnosis has an impact on patient outcome, especially in terms of the treatment options available. Most patients will receive at least three lines of treatment, and eligible patients will receive stem cell transplantation.
Latest key takeaways
- Datamonitor Healthcare estimates that in 2018, there were 134,100 incident cases of multiple myeloma (MM) in adults aged 40 years and older worldwide, and expects that number to increase to 153,700 incident cases by 2027.
- The launch of BCMA-targeted therapies will play a pivotal part in future market dynamics over the next decade. Key new product launches will include the antibody-drug conjugate (ADC) Blenrep and the CAR-T therapies ide-cel and JNJ-4528. Given the unmet need for effective therapies for heavily pretreated patients, uptake is expected to be rapid.
- Revlimid, a thalidomide analog, and Velcade, a proteasome inhibitor (PI), are key therapies across patient segments, both as monotherapies and as backbones for combination regimens. These drugs have broad approvals across all markets, and the expected expiry of their patents will exert substantial downward pressure on the MM market.
- Darzalex, the first monoclonal antibody (MAb) approved for MM, has experienced steady uptake and has become a new standard of care based on impressive trial results in the relapsed/refractory MM (RRMM) setting. The drug, a CD38-targeted MAb, will experience continual commercial success due to several label expansions in the newly diagnosed MM and RRMM settings, as well as the recent approval of a more convenient subcutaneous formulation.
- Sarclisa, another CD38-directed MAb, is expected to face intense in-class competition from Darzalex, especially in the relapsed/refractory setting where Sarclisa gained its first approval as a treatment for RRMM patients who have received at least two prior therapies. Although Sarclisa is currently relegated to the highly competitive later lines of therapy, where it will also compete with Farydak, Empliciti, and Velcade, label expansions to earlier treatment settings will expand its commercial potential.
- Bristol Myers Squibb, which also markets Revlimid, has positioned Pomalyst as a subsequent therapy option. Pomalyst, another thalidomide analog, adds a treatment option to Bristol Myers Squibb’s MM portfolio, but faces increasing competition in the late-stage treatment setting from a number of approved and pipeline therapies.
- Second-generation PI Kyprolis is approved for the treatment of RRMM as a monotherapy and in combination with either dexamethasone, Darzalex and dexamethasone, or Revlimid and dexamethasone. Kyprolis remains the favored PI in the RRMM setting as it demonstrated improved safety and efficacy over Velcade, another PI, in the Phase III ENDEAVOR trial. However, unlike Velcade, Kyprolis does not offer a subcutaneous formulation.
- In combination with Revlimid and dexamethasone, Ninlaro, the first oral PI approved by the FDA, is part of an all-oral regimen approved for the treatment of patients with relapsed MM with one prior line of therapy. Ninlaro has seen consistent sales in the MM market due to its convenient administration, a competitive price, and the combination’s relatively favorable safety profile.
- Empliciti, the only SLAMF7-targeted MAb approved for MM, has seen moderate uptake since the combination of Empliciti, Revlimid, and dexamethasone (ERd) was approved for the treatment of MM patients who have received one to three prior lines of therapy. A label expansion in combination with Pomalyst and dexamethasone for the treatment of MM patients who have received at least two prior therapies provided expanded options for the use of Empliciti in the treatment of RRMM, but did not significantly improve the drug’s commercial potential in this crowded treatment space.
- The XPO1 inhibitor Xpovio represents the first novel mechanism approved for MM since the approval of the anti-SLAMF7 antibody Empliciti. Xpovio in combination with dexamethasone is approved in the US for patients with RRMM who have received at least four prior therapies and whose disease is refractory to at least two PIs, at least two immunomodulatory agents, and an anti-CD38 MAb. Given the small patient population, Xpovio has experienced only limited uptake, although label expansions to earlier treatment settings will expand the drug’s commercial potential.
- Ygalo is in the BLA phase as a treatment for patients with triple-refractory MM, but this novel dipeptide prodrug of melphalan has only a modest commercial outlook given it will face significant competition from both approved and late-phase competitors in an increasingly crowded market. Although Ygalo demonstrated a 26% overall response rate in the registrational Phase II HORIZON study, the BCMA-directed therapies have shown better efficacy results. Ygalo is also being developed for earlier lines of therapy, where it may find greater commercial success.
- Venclexta is positioned to be approved for a limited subset of RRMM patients. The FDA placed a clinical hold on all Venclexta trials in MM after the Phase III BELLINI study showed a higher mortality rate in patients treated with the combination of Venclexta, Velcade, and dexamethasone than in patients treated with Velcade/dexamethasone. However, the FDA lifted the partial clinical hold exclusively for the Phase III CANOVA study of Venclexta in combination with dexamethasone for the treatment of patients with RRMM positive for the translocation (11;14) abnormality, and topline results from the trial are expected in 2021.
- Key recent events include Blenrep’s approval in the US and EU for heavily pretreated MM, approval of a subcutaneous formulation of Darzalex, and two Phase III failures: Ninlaro in the induction setting (TOURMALINE-MM2), and Kyprolis in an ECOG study comparing Kyprolis or Velcade combined with Revlimid and dexamethasone (KRd vs VRd) in front-line MM. Other key events include Ygalo’s success in the pivotal Phase II HORIZON study as a treatment for triple-refractory MM, and two Phase III successes for second-line or later MM: Sarclisa’s success in IKEMA in combination with Kyprolis and dexamethasone, and Xpovio’s success in BOSTON in combination with Velcade and dexamethasone.
- Key upcoming catalysts for the next year include the expected US approvals of ide-cel and Ygalo, and label expansions in the US for Xpovio.
- The overall likelihood of approval of a Phase I MM asset is 6.9%, and the average probability a drug advances from Phase III is 58.3%. MM drugs, on average, take 8.6 years from Phase I to approval, compared to 9.4 years in the overall oncology space.
CONTENTS
9 OVERVIEW
9 Latest key takeaways
11 DISEASE BACKGROUND
11 Definition
11 Risk factors
11 Presentation
12 Symptoms
13 Diagnosis
14 Patient segmentation
15 Co-morbidities
16 Subtypes
19 TREATMENT
19 Smoldering multiple myeloma
19 Active multiple myeloma
23 EPIDEMIOLOGY
27 MARKETED DRUGS
32 PIPELINE DRUGS
48 KEY REGULATORY EVENTS
48 GSK’s Blenrep Wins BCMA Race, Carries Ocular Toxicity Warning
48 EMA Says Yes To GSK’s Belantamab
48 GSK’s Myeloma Drug Gets AdComm Backing, But Limitations Remain Clear
48 Concerns About Eye Toxicity Could Limit GSK’s Myeloma Drug Potential
49 Sanofi Is ‘Working On’ Resolving England’s Sarclisa Funding Concerns
49 New EU Approvals
49 Manufacturing Issues Ground bluebird/Bristol ‘Ide-Cel’ CAR-T
49 Approval For New Darzalex Dosing
50 Xpovio Avoided Complete Response Letter Through Late-Cycle Submission Of BOSTON Data
50 UK Multiple Myeloma Patients Allowed Early Access To Sanofi’s Isatuximab
50 GSK Files Its BCMA Drug In Multiple Myeloma
50 Celgene Gets Another Myeloma CAR-T Accepted Onto EMA’s PRIME
51 EU Approvals: J&J’s Darzalex Steps Ahead With New Indication
51 Karyopharm’s Xpovio In Multiple Myeloma Priced At $22,000 Per Four-Week Cycle
52 PROBABILITY OF SUCCESS
53 LICENSING AND ASSET ACQUISITION DEALS
53 Kiadis And Sanofi Sign Natural Killer Cell Therapy Pact
53 Bluebird Revises Business Priorities And Secures Upfront Cash From Bristol
53 Harpoon Finds A Blood Cancer Partner In AbbVie
53 Amgen Joins China Oncology Market Race With $2.7bn BeiGene Stake
55 CLINICAL TRIAL LANDSCAPE
56 Sponsors by status
57 Sponsors by phase
58 Recent events
63 DRUG ASSESSMENT MODEL
68 MARKET DYNAMICS
69 FUTURE TRENDS
69 Genericization of key brands Revlimid and Velcade will substantially slow market growth
69 New BCMA-targeted therapies will contribute to growth in the multiple myeloma market over the forecast period
70 Label expansions of marketed drugs will help balance out downturn in the market
70 The growth of pipeline and newly approved drugs in the relapsed/refractory setting will be dependent on label expansions
to earlier lines of therapy
72 CONSENSUS FORECASTS
76 RECENT EVENTS AND ANALYST OPINION
76 Darzalex for Multiple Myeloma (July 31, 2020)
76 Blenrep for Multiple Myeloma (July 14, 2020)
78 Blenrep for Multiple Myeloma (July 10, 2020)
79 UCARTS1 for Multiple Myeloma (July 6, 2020)
80 Sarclisa for Multiple Myeloma (June 2, 2020)
81 Kyprolis for Multiple Myeloma (May 31, 2020)
83 Sarclisa for Multiple Myeloma (May 31, 2020)
85 CC-92480 for Multiple Myeloma (May 31, 2020)
87 Orvacabtagene Autoleucel for Multiple Myeloma (May 30, 2020)
88 JNJ-64007957 for Multiple Myeloma (May 29, 2020)
90 Xpovio for Multiple Myeloma (May 28, 2020)
92 Blenrep for Multiple Myeloma (May 27, 2020)
94 Ide-cel for Multiple Myeloma (May 13, 2020)
95 Sarclisa for Multiple Myeloma (May 12, 2020)
97 Ygalo for Multiple Myeloma (March 26, 2020)
98 Ninlaro for Multiple Myeloma (March 10, 2020)
100 Empliciti for Multiple Myeloma (March 9, 2020)
101 Xpovio for Multiple Myeloma (March 2, 2020)
103 Blenrep for Multiple Myeloma (December 16, 2019)
105 Darzalex for Multiple Myeloma (December 10, 2019)
107 C-CAR088 for Multiple Myeloma (December 7, 2019)
108 CC-93269 for Multiple Myeloma (December 7, 2019)
110 JNJ-4528 for Multiple Myeloma (December 7, 2019)
111 ide-cel for Multiple Myeloma (December 6, 2019)
113 Ninlaro for Multiple Myeloma (November 7, 2019)
114 Daratumumab-rHuPH20 (Subcutaneous) for Multiple Myeloma (September 15, 2019)
116 Multiple Drugs for Multiple Myeloma (September 13, 2019)
117 Blenrep for Multiple Myeloma (August 23, 2019)
118 CERC-007 for Multiple Myeloma (August 7, 2019)
119 Darzalex for Multiple Myeloma (July 8, 2019)
121 Xpovio for Multiple Myeloma (July 3, 2019)
122 GEN3014 for Multiple Myeloma (June 11, 2019)
123 Sarclisa for Multiple Myeloma (June 2, 2019)
125 AMG 420 for Multiple Myeloma (June 2, 2019)
127 Darzalex for Multiple Myeloma (June 2, 2019)
129 Iberdomide for Multiple Myeloma (June 2, 2019)
130 Darzalex for Multiple Myeloma (June 2, 2019)
133 Iberdomide for Multiple Myeloma (May 15, 2019)
136 KEY UPCOMING EVENTS
137 KEY OPINION LEADER INSIGHTS
139 UNMET NEEDS
140 BIBLIOGRAPHY
141 Prescription information
143 APPENDIX
LIST OF FIGURES
22 Figure 1: Recommended treatment regimens for relapsed/refractory multiple myeloma
25 Figure 2: Trends in incident cases of multiple myeloma, 2018–27
32 Figure 3: Overview of pipeline drugs for multiple myeloma in the US
32 Figure 4: Pipeline drugs for multiple myeloma, by company
33 Figure 5: Pipeline drugs for multiple myeloma, by drug type
33 Figure 6: Pipeline drugs for multiple myeloma, by classification
52 Figure 7: Probability of success in the multiple myeloma pipeline
55 Figure 8: Clinical trials in multiple myeloma
55 Figure 9: Top 10 drugs for clinical trials in multiple myeloma
56 Figure 10: Top 10 companies for clinical trials in multiple myeloma
56 Figure 11: Trial locations in multiple myeloma
57 Figure 12: Multiple myeloma trials status
58 Figure 13: Multiple myeloma trials sponsors, by phase
63 Figure 14: Datamonitor Healthcare’s drug assessment summary for multiple myeloma
68 Figure 15: Market dynamics in multiple myeloma
69 Figure 16: Future trends in multiple myeloma
81 Figure 17: Sarclisa for Multiple Myeloma (June 2, 2020): Phase III – IKEMA (w/Carfilzomib+Dex)
83 Figure 18: Kyprolis for Multiple Myeloma (May 31, 2020): Phase III – ECOG Study – w/Bortezomib/Lenalidomide/Dexamethasone (VRd)
85 Figure 19: Sarclisa for Multiple Myeloma (May 31, 2020): Phase II – GMMG-CONCEPT
88 Figure 20: Orvacabtagene Autoleucel for Multiple Myeloma (May 30, 2020): Phase I/II – EVOLVE
90 Figure 21: JNJ-64007957 for Multiple Myeloma (May 29, 2020): Phase I – CR108206
92 Figure 22: Xpovio for Multiple Myeloma (May 28, 2020): Phase III – BOSTON
94 Figure 23: Blenrep for Multiple Myeloma (May 27, 2020): Phase II – DREAMM-6 (2L)
97 Figure 24: Sarclisa for Multiple Myeloma (May 12, 2020): Phase III – IKEMA (w/Carfilzomib+Dex)
98 Figure 25: Ygalo for Multiple Myeloma (March 26, 2020): Phase II – HORIZON
100 Figure 26: Ninlaro for Multiple Myeloma (March 10, 2020): Phase III – TOURMALINE-MM2 (w/Len/Dex (First Line))
101 Figure 27: Empliciti for Multiple Myeloma (March 9, 2020): Phase III – ELOQUENT-1
103 Figure 28: Xpovio for Multiple Myeloma (March 2, 2020): Phase III – BOSTON
105 Figure 29: Blenrep for Multiple Myeloma (December 16, 2019): Phase II – DREAMM 2 (4L)
107 Figure 30: Darzalex for Multiple Myeloma (December 10, 2019): Phase III – CANDOR (w/Kyprolis+Dex)
111 Figure 31: JNJ-4528 for Multiple Myeloma (December 7, 2019): Phase Ib/II – CARTITUDE-1 (Dose Finding)
113 Figure 32: ide-cel for Multiple Myeloma (December 6, 2019): Phase II – KarMMa
114 Figure 33: Ninlaro for Multiple Myeloma (November 7, 2019): Phase III – TOURMALINE-MM4
116 Figure 34: Daratumumab-rHuPH20 (Subcutaneous) for Multiple Myeloma (September 15, 2019): Phase II – PLEIADES
117 Figure 35: Darzalex and Kyprolis for Multiple Myeloma (September 13, 2019): Phase III – CANDOR (w/Darzalex+Dex)
118 Figure 36: Blenrep for Multiple Myeloma (August 23, 2019): Phase II – DREAMM 2 (4L)
121 Figure 37: Darzalex for Multiple Myeloma (July 8, 2019): Phase II – GRIFFIN (vs. RVd)
125 Figure 38: Sarclisa for Multiple Myeloma (June 2, 2019): Phase III – ICARIA-MM (w/PomDex)
127 Figure 39: AMG 420 for Multiple Myeloma (June 2, 2019): Phase I – PK/PD
129 Figure 40: Darzalex for Multiple Myeloma (June 2, 2019): Phase III – COLUMBA (vs. SC)
130 Figure 41: Iberdomide for Multiple Myeloma (June 2, 2019): Phase Ib/IIa – MM-001 (w/Dexamethasone)
133 Figure 42: Darzalex for Multiple Myeloma (June 2, 2019): Phase III – Cassiopeia – w/Bortezomib/Thalidomide/Dexamethasone (MMY3006)
135 Figure 43: Iberdomide for Multiple Myeloma (May 15, 2019): Phase Ib/IIa – MM-001 (w/Dexamethasone)
136 Figure 44: Key upcoming events in multiple myeloma
LIST OF TABLES
12 Table 1: Diagnostic criteria for MGUS and smoldering multiple myeloma
13 Table 2: Symptoms of advanced multiple myeloma
14 Table 3: ISS criteria for multiple myeloma
15 Table 4: R-ISS criteria for multiple myeloma
16 Table 5: Common co-morbidities associated with multiple myeloma
17 Table 6: Common cytogenetic abnormalities associated with multiple myeloma
24 Table 7: Incident cases of multiple myeloma, 2018–27
26 Table 8: Incident cases of multiple myeloma, by gender, 2018
28 Table 9: Marketed drugs for multiple myeloma
34 Table 10: Pipeline drugs for multiple myeloma
72 Table 11: Historical global sales, by drug ($m), 2015–19
73 Table 12: Forecasted global sales, by drug ($m), 2020–24
76 Table 13: Darzalex for Multiple Myeloma (July 31, 2020)
77 Table 14: Blenrep for Multiple Myeloma (July 14, 2020)
78 Table 15: Blenrep for Multiple Myeloma (July 10, 2020)
79 Table 16: UCARTS1 for Multiple Myeloma (July 6, 2020)
80 Table 17: Sarclisa for Multiple Myeloma (June 2, 2020)
82 Table 18: Kyprolis for Multiple Myeloma (May 31, 2020)
84 Table 19: Sarclisa for Multiple Myeloma (May 31, 2020)
86 Table 20: CC-92480 for Multiple Myeloma (May 31, 2020)
87 Table 21: Orvacabtagene Autoleucel for Multiple Myeloma (May 30, 2020)
89 Table 22: JNJ-64007957 for Multiple Myeloma (May 29, 2020)
91 Table 23: Xpovio for Multiple Myeloma (May 28, 2020)
92 Table 24: Blenrep for Multiple Myeloma (May 27, 2020)
94 Table 25: Ide-cel for Multiple Myeloma (May 13, 2020)
96 Table 26: Sarclisa for Multiple Myeloma (May 12, 2020)
97 Table 27: Ygalo for Multiple Myeloma (March 26, 2020)
99 Table 28: Ninlaro for Multiple Myeloma (March 10, 2020)
100 Table 29: Empliciti for Multiple Myeloma (March 9, 2020)
102 Table 30: Xpovio for Multiple Myeloma (March 2, 2020)
104 Table 31: Blenrep for Multiple Myeloma (December 16, 2019)
106 Table 32: Darzalex for Multiple Myeloma (December 10, 2019)
108 Table 33: C-CAR088 for Multiple Myeloma (December 7, 2019)
109 Table 34: CC-93269 for Multiple Myeloma (December 7, 2019)
110 Table 35: JNJ-4528 for Multiple Myeloma (December 7, 2019)
112 Table 36: ide-cel for Multiple Myeloma (December 6, 2019)
113 Table 37: Ninlaro for Multiple Myeloma (November 7, 2019)
115 Table 38: Daratumumab-rHuPH20 (Subcutaneous) for Multiple Myeloma (September 15, 2019)
116 Table 39: Multiple Drugs for Multiple Myeloma (September 13, 2019)
117 Table 40: Blenrep for Multiple Myeloma (August 23, 2019)
119 Table 41: CERC-007 for Multiple Myeloma (August 7, 2019)
120 Table 42: Darzalex for Multiple Myeloma (July 8, 2019)
121 Table 43: Xpovio for Multiple Myeloma (July 3, 2019)
122 Table 44: GEN3014 for Multiple Myeloma (June 11, 2019)
123 Table 45: Sarclisa for Multiple Myeloma (June 2, 2019)
126 Table 46: AMG 420 for Multiple Myeloma (June 2, 2019)
128 Table 47: Darzalex for Multiple Myeloma (June 2, 2019)
129 Table 48: Iberdomide for Multiple Myeloma (June 2, 2019)
131 Table 49: Darzalex for Multiple Myeloma (June 2, 2019)
134 Table 50: Iberdomide for Multiple Myeloma (May 15, 2019)
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