July 22, 2020

Impact: High

  • GENFIT has officially terminated its pivotal RESOLVE-IT trial of elafibranor for the treatment of NASH with fibrosis after it failed an interim analysis back in May.
  • The trial did not meet the predefined primary surrogate efficacy endpoint of NASH resolution without worsening of fibrosis in the ITT population of 1,070 patients.
  • Following a detailed review of the full interim efficacy dataset, GENFIT determined that the investment needed to continue the trial was not justified, as it was unlikely to support a regulatory filing.
  • The company plans to share key learnings, including upcoming results from the second reading of liver biopsies that will help better understand inter-reader variability and its impact.
  • GENFIT will continue to develop elafibranor in primary biliary cholangitis (PBC) and is committed to initiate a phase 3 program following positive phase 2 data in this indication. The company will announce its updated corporate strategy in September 2020.

Read more

July 17, 2020

Impact: Moderate

  • ADC Therapeutics has dosed the first patient in the pivotal phase 2 portion of its phase 1/2 LOTIS 3 trial (NCT03684694) of loncastuximab tesirine plus ibrutinib in R/R DLBCL or MCL (Mantle Cell Lymphoma).
  • The phase 2 portion is to enroll three cohorts: non-germinal center B cell (GCB)-like DLBCL, GCB DLBCL, and MCL.
  • Interim data for the phase 1 portion was presented at EHA 2020, as follows:
    • Overall response rate (ORR): 75% (complete response [CR] rate: 58.3%)
    • Grade ≥3 treatment-emergent adverse events (TRAE): thrombocytopenia (20%), anemia (12%).
    • Recommended phase 2 dose: 60 µg/kg.

Read more

July 8, 2020

Impact: High

  • FDA has issued a CRL (Complete Response Letter) in response to the sBLA for the combination of Keytruda/Lenvima (pembrolizumab/lenvatinib) to treat first-line (1L) unresectable HCC (hepatocellular carcinoma). This application was supported by Merck and Eisai.
  • The application was based on data from the phase 1b single-arm KEYNOTE-524 (Study 116; NCT03006926) trial. The combination had previously received Breakthrough Therapy Designation and the companies sought Accelerated Approval. Key efficacy data from -524 were presented at ASCO 2020 and included:
    • mOS: 22 months
    • ORR (Objective Response Rate): 36% (CR rate: 1%)
    • mDoR (median Duration of Response): 12.6 months
  • According to the press release, the main reason for the CRL was that Keytruda/Lenvima did not represent a meaningful advantage over currently available therapies in 1L HCC. Notably, the combination of Tecentriq/Avastin (atezolizumab/bevacizumab) in 1L HCC was approved 4 weeks earlier on the basis of benefits observed for mOS (median Overall Survival) and mPFS (median Progression-Free Survival) in a phase 3 active comparator study.
  • Merck/Eisai still plan to submit for a full approval of Keytruda/Lenvima based on the LEAP-002 trial in 1L HCC. This trial is fully enrolled.

  Read more

July 2, 2020

Impact: High

Regeneron and Sanofi have announced that a Regeneron-led phase 3 U.S. trial of Kevzara (sarilumab) in patients with COVID-19 failed to meet its primary or key secondary endpoints and has been stopped early. 

The adaptive-design trial was enrolling patients with severe or critical COVID-19. The primary endpoint was a ≥1-point improvement on a 7-point ordinal scale in critical patients who were receiving mechanical ventilation at baseline; 194 patients were evaluable for the primary analysis. Patients had received Kevzara 400mg or placebo in addition to standard of care (SOC). 

The interim results showed minor positive trends with Kevzara in the primary analysis group, but statistical significance was not achieved and the positive trends were outweighed by negative trends in a subgroup of critical patients who were not receiving mechanical ventilation at baseline.

Based on these outcomes, the trial has been stopped, including a partially enrolled, higher dose cohort (800mg). Detailed results will be submitted to a peer-reviewed journal for publication later in the year. 

A separate Sanofi-led trial outside of the U.S. evaluating a different Kevzara regimen in patients with severe or critical disease is ongoing. The same Independent Data Monitoring Committee is overseeing both trials and has recommended continuation of the ex-U.S. trial. Results are expected in Q3 2020. Read more