Multiple Myeloma Disease Coverage Forecast and Market Analysis

Multiple Myeloma Disease Coverage Forecast and Market Analysis

  • March 2021 •
  • 142 pages •
  • Report ID: 5975647 •
  • Format: PDF
Disease Analysis
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

The analyst 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.
Revlimid, an immunomodulatory drug (IMiD), and Velcade, a proteasome inhibitor (PI), play key roles as the backbone for combination regimens across various lines of therapy. These drugs have broad approvals in all markets, and the expected expiry of their patents in 2022 will exert substantial downward pressure on the MM market.
The launch of BCMA-targeted therapies will play a pivotal part in future market dynamics over the next decade. The antibody-drug conjugate (ADC) Blenrep is approved for triple-class exposed patients that have been treated with at least four prior therapies including a PI, an IMiD, and an anti-CD38 monoclonal antibody (MAb). Blenrep is also being evaluated in Phase III trials for earlier lines of therapy. Other key anti-BCMA agents include the CAR-T therapies ide-cel and JNJ-4528, which are under regulatory review for triple-refractory MM. Given the unmet need for effective therapies for heavily pretreated patients, uptake is expected to be rapid.
Darzalex, the first 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 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, subsequent 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 IMiD, adds a treatment option to Bristol Myers Squibb’s MM portfolio. Generic versions of Pomalyst received final approval from the FDA in October 2020, but patent litigation continues and it is not yet clear when these generics will launch. Pomalyst has regulatory exclusivity until 2023 in the EU and until 2025 in Japan.
Second-generation PI Kyprolis is approved for the treatment of RRMM as a monotherapy and in combination with either dexamethasone (dex), Darzalex and dex, or Revlimid and dex. 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 the front-line setting, a Kyprolis regimen (Kyprolis, Revlimid and dex; KRd) failed to show superiority to a Velcade regimen (VRd). Nevertheless, the KRd regimen will likely continue to see some off-label use in the front-line setting due to KRd and VRd having different toxicity profiles.
In combination with Revlimid and dex, 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 dex (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 dex 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 was the first novel mechanism approved for MM since the approval of the anti-SLAMF7 antibody Empliciti. Xpovio in combination with dex is approved in the US for MM patients who have received at least four prior therapies and who are penta-refractory (refractory to at least two PIs, two IMiDs, and an anti-CD38 antibody). A European approval for the doublet is expected during Q1 2021 following a positive CHMP assessment. In December 2020, Xpovio was approved by the FDA as part of a triple combination with Velcade and dex in the second- to fourth-line settings. This label expansion should help expand Xpovio’s commercial potential, but it will still face significant competition from established brands.
Pepaxto is a novel dipeptide prodrug of the alkylating agent melphalan. Pepaxto in combination with dex is approved in the US for triple-refractory MM patients who have received at least four prior therapies. In this setting, Pepaxto will compete with Xpovio combined with dex and with Blenrep monotherapy. Pepaxto may be preferred for patients with extramedullary disease as they comprised 41% of patients in the registrational trial (compared to 22% for Xpovio and 20% for Blenrep). Pepaxto is also being developed for earlier lines of therapy, which will increase its commercial potential.
There are four bispecific antibodies being evaluated in pivotal Phase II trials for fourth-line or later multiple myeloma: Pfizer’s elranatamab, Regeneron’s REGN5458, and Johnson and Johnson’s teclistamab and talquetamab. Three of the bispecifics target BCMA x CD3, while talquetamab is specific for CD3 and the novel target GPRC5D. Pivotal data are expected in January 2022 for teclistamab, while elranatamab and REGN5458 are expected to read out in June 2022 and December 2022, respectively. Talquetamab’s pivotal data are expected in September 2023.
Iberdomide is a next-generation IMiD being developed by Bristol Myers Squibb, and binds the E3 ligase cereblon with higher affinity than Revlimid and Pomalyst. A pivotal Phase II cohort is evaluating iberdomide combined with dex in triple-refractory fourth-line or later patients (excluding post-BCMA patients), and data are expected in H2 2021.
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 the Venclexta, Velcade, and dex arm compared to patients in the Velcade/dex arm. However, the FDA lifted the partial clinical hold exclusively for the Phase III CANOVA study of Venclexta in combination with dex for RRMM patients positive for the translocation (11;14) abnormality. Topline results from the trial are expected during 2021.
Key recent events include the approvals of Blenrep (US and EU), a subcutaneous formulation of Darzalex (US and EU), and Pepaxto (US). There were 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 dex (KRd vs VRd) in front-line MM.
Other key recent events include two Phase III successes for second-line or later MM: Sarclisa’s success in IKEMA in combination with Kyprolis and dex, and Xpovio’s success in BOSTON in combination with Velcade and dex.
Key upcoming catalysts for 2021 include the expected US approvals of the BCMA-directed CAR-T therapies ide-cel and JNJ-4528. Supplementary approvals are expected in second-line or later MM for Sarclisa combined with Kyprolis and dex, and subcutaneous Darzalex combined with Pomalyst and dex.
The overall likelihood of approval of a Phase I MM asset is 6.6%, and the average probability a drug advances from Phase III is 56%. MM drugs, on average, take 9.0 years from Phase I to approval, compared to 9.6 years in the overall oncology space.