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NEWS AND PUBLICATIONS

Novartis 177Lu-PSMA-617 shows significant clinical benefit based on VISION trial results

This Phase 3 trial investigates 77Lu-PSMA-617, a targeted radioligand therapy, plus best standard of care (SOC) compared to SOC alone, in patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). Adding 177Lu-PSMA-617 to standard of care (SOC) after androgen receptor pathway inhibition and chemotherapy extended overall survival (OS) and delayed radiographic progression-free survival (rPFS), chosen as alternate primary endpoints (NCT03511664).

Despite recent advances, mCRPC, therapeutic options remain limited with low survival numbers. Prostate-specific membrane antigen (PSMA) is highly expressed in mCRPC lesions and presents a suitable molecule for targeted therapies. Lu-PSMA-617 is a targeted radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and surrounding microenvironment. In the VISION trial, patients were randomly assigned 2:1 to 177Lu-PSMA-617 (7.4 GBq every 6 weeks × 6 cycles) plus SOC vs SOC alone. 177Lu-PSMA-617 plus SOC significantly improved rPFS vs SOC alone (median rPFS, 8.7 months vs 3.4 months). OS was also significantly improved vs SOC alone (median OS, 15.3 months vs 11.3 months). The results were presented at the ASCO meeting in June.

First cell-based gene therapy to treat adult patients with multiple myeloma

With no treatments and only few options available for multiple myeloma patients, the first CAR-T medicines in multiple myeloma gained further approval. This CAR-T therapy targets the B-cell maturation antigen-targeted (BCMA). It’s approved for adults whose multiple myeloma has progressed after at least four previous rounds of treatment (by FDA in March 2021; EMA with conditional marketing authorization in June 2021). Abecma (idecabtagene vicleucel) is a BCMA-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose of Abecma is a customized treatment created by using a patient’s own T-cells. In a phase 2 study (KarMMa), the efficacy and safety of idecabtagene vicleucel in patients with relapsed and refractory myeloma was confirmed. Patients received idecabtagene vicleucel target doses of 150×106 to 450×106 CAR-positive (CAR+) T cells. The primary end point was an overall response (partial response or better); a key secondary end point was a complete response or better (comprising complete and stringent complete responses). Of 140 patients enrolled, 128 received treatment. At the median follow-up of 13.3 months, 94 of 128 patients (73%) had a response, and 42 of 128 (33%) had a complete response or better. The median progression-free survival was 8.8 months (95% confidence interval, 5.6 to 11.6). Cytokine release syndrome was reported in 107 patients (84%), including 7 (5%) who had events of grade 3 or higher. Neurotoxic effects developed in 23 patients (18%) and were of grade 3 in 4 patients (3%); no neurotoxic effects higher than grade 3 occurred. Cellular kinetic analysis confirmed CAR+ T cells in 29 of 49 patients (59%) at 6 months and 4 of 11 patients (36%) at 12 months after infusion.

INDUSTRY

Blackstone Life Sciences, Cellex Cell Professionals, and Intellia Therapeutics Launch a New CAR T-Cell Company

Blackstone, one of the world’s largest investment firms, is joining forces with gene editing drugmaker Intellia Therapeutics and a German cell manufacturer to launch a new biotechnology company focused on developing cell therapies for cancer and autoimmune diseases. Blackstone will contribute $250 million to the new, yet unnamed company.

Intellia and Cellex, the German manufacturer, will own equal shares in the new company, which aims to pair CRISPR gene editing technology developed by Intellia with a CAR-T cell therapy platform built by Cellex subsidiary GEMoaB. As a result of the deal, the new company will acquire GEMoaB. GEMoaB is developing a switchable universal platform to improve the therapeutic window of CAR T-cell therapies. This approach enables increased efficacy and safety across a range of cancers, including solid tumors, that are currently a challenge for existing cell therapies. In addition, the new company and Intellia will gain access to Cellex’s established cell therapy manufacturing capabilities to accelerate their respective ex vivo programs.

EMA

In June, the Committee for Medical Products for Human Use (CHMP) adopted a positive opinion for:

New Medicines:

  • Abecma (idecabtagene vicleucel; Celgene Europe BV) intended for the treatment of relapsed and refractory multiple myeloma. As Abecma is an advanced therapy medicinal product, the CHMP’s positive opinion is based on an assessment by the Committee for Advanced Therapies. Abecma will be available as a 260-500 x 10⁶ CAR-positive viable T cells dispersion for infusion. The active substance of Abecma is idecabtagene vicleucel, a chimeric antigen receptor (CAR)-positive T cell therapy targeting B-cell maturation antigen (BCMA), which is expressed on the surface of normal and malignant plasma cells. Antigen-specific activation of Abecma results in CAR-positive T cell proliferation, cytokine secretion and subsequent cytolytic killing of BCMA-expressing cells.
  • Minjuvi (tafasitamab; Incyte Biosciences Distribution BV) intended for the treatment of adult patients with relapsed or refractory diffuse large B‑cell lymphoma (DLBCL) who are not eligible for autologous stem-cell transplant (ASCT). The active substance of Minjuvi is a monoclonal antibody that targets the CD19 antigen expressed on the surface of pre-B and mature B lymphocytes. Upon binding to CD19, tafasitamab mediates B-cell lysis through effector cells of the immune system, such as natural killer cells, gammadelta T cells and phagocytes, and direct induction of cell death (apoptosis).

New Generic Medicine:

  • Abiraterone Mylan (Mylan Ireland Limited) intended for the treatment of metastatic prostate cancer. The active substance of Abiraterone Mylan is abiraterone acetate, a hormone antagonist (ATC code: L02BX03) that inhibits the production of androgens in the testes, adrenal glands and prostatic tumor tissues.

Extensions of indications:

  • Opdivo (nivolumab; Bristol-Myers Squibb Pharma EEIG) as monotherapy indicated for the adjuvant treatment of adult patients with esophageal or gastro-esophageal junction cancer who have residual pathologic disease following prior neoadjuvant chemoradiotherapy.

Updated recommendations on eligibility for PRIME (up to June2021) for oncology products show 27 applications accepted and 80 applications denied.

FDA

In June, the FDA granted approval for:

  • Avapritinib (Ayvakit™, Blueprint Medicines Corp.) for adult patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL). 

FDA guidance documents of interest:

Sponsor Responsibilities – Safety Reporting Requirements and Safety Assessment for IND and Bioavailability/Bioequivalence Studies

This draft guidance provides recommendations to help sponsors comply with the expedited safety reporting requirements for human drug and biological products that are being investigated (1) under an investigational new drug application (IND) (21 CFR 312.32) or (2) as part of a bioavailability (BA) or bioequivalence (BE) study that is exempt from the IND requirements (21 CFR 312.64(b) and 320.31(d)(3)). This draft guidance defines terms used for safety reporting, makes recommendations on when and how to submit a safety report, and provides information on other safety reporting issues raised by sponsors.

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