February 7, 2020

Impact: Moderate

  • Innovent Biologics and Eli Lilly have announced that the phase 3 ORIENT-11 trial (NCT03607539) in China has met its primary endpoint of progression-free survival (PFS) for the use of Tyvyt (sintilimab) in combination with ALTIMA (pemetrexed) and platinum-based chemotherapy for patients with 1L advanced or recurrent nonsquamous NSCLC without EGFR mutations or ALK rearrangements tumors, when compared to placebo.
  • The safety profile of Tyvyt was consistent with previous studies, and no new safety signals emerged.
  • Based on this data, Innovent and Eli Lilly plan to initiate regulatory discussions with China’s National Medical Products Administration (NMPA) in the near future.
  • Data will be presented at an upcoming medical conference.

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December 18, 2019

Impact: Moderate

  • Gilead’s Kite subsidiary has announced that it has submitted a BLA for the investigational CAR-T KTE-X19 for the treatment of patients with relapsed or refractory mantle cell lymphoma (R/R MCL).
  • The BLA is based on data from the Phase 2 ZUMA-2 trial which demonstrated an ORR of 93% (CR rate = 67%) in 60 evaluable patients. Enrolled patients had MCL that was refractory to or had relapsed following up to 5 prior lines of therapy.
  • Grade 3 or higher cytokine release syndrome (CRS) and neurotoxicity were seen in 15% and 31% of patients, respectively. No Grade 5 CRS or neurological events were observed.
  • Detailed findings from ZUMA-2 were presented Monday at ASH 2019.
  • KTE-X19 has been granted FDA Breakthrough Therapy and EMA PRIME status for the MCL indication.
  • Kite anticipates submitting a European Marketing Authorization Application in early 2020.

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December 5, 2019

Impact: High

  • CymaBay Therapeutics has terminated its phase 2b study of PPARδ agonist, seladelpar, in patients with NASH due to atypical histological findings.
  • Planned, blinded histological assessments of liver biopsies from trial participants revealed histology characterized as an interface hepatitis presentation, with or without biliary injury.
  • Notably, the atypical histological findings were observed in patients who demonstrated on-study improvement or stabilization of their biochemical measures of inflammation and liver injury and none of these patients experienced liver-related adverse events after 52 weeks of treatment. Evaluation is ongoing to better understand these findings.
  • The company also terminated its recently initiated phase 2 study of seladelpar in primary sclerosing cholangitis (PSC), and all studies in primary biliary cholangitis (PBC) have been placed on clinical hold.

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October 31, 2019

Impact: High

  • China regulators have cleared the IND for the fully human BCMA CAR-T, CT-103A, in development by Nanjing Iaso and Innovent Biologics.
  • In the recent issue of BioWorld (pages 1 & 6), Brian Hall, VP of Business Development at Iaso, stated that a phase 1b/2 trial to confirm the recommended phase 2 dose is planned to start 1Q20 and will enroll 60-70 patients. Hall also notes a CT-103A approval is planned in 2H21.
  • In the investigator-initiated trial at Tongji Hospital, CT-103A treatment led to an ORR of 100% (sCR: 71%, CR: 88%) and four patients who relapsed on a previous murine BCMA CAR-T therapy have all achieved > VGPR. Onset of CRS occurred within 2-5 days and resolved within two weeks.

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October 31, 2019

Impact: High

In March this year, the aducanumab phase 3 Alzheimer’s disease trials were stopped based on futility, meaning that it was statistically almost impossible for the study to meet its endpoint. The operative word was apparently “almost.”

Full analysis of the phase 3 results now shows that the high dose arm of aducanumab, an anti-amyloid antibody, did indeed meet its primary and secondary endpoints, demonstrating significantly slower cognitive decline than the placebo group by CDR-sum of boxes (23% difference at 1.5 years, p=0.01 vs. placebo in the EMERGE trial). Aducanumab was also associated with reduction in brain amyloid. Safety was “consistent with earlier studies.”

Based on these results, Biogen and Eisai will file for aducanumab approval in early 2020, and are also restarting the extension studies of aducanumab. Aducanumab could be marketed as the first approved disease modifying Alzheimer’s disease drug by the end of 2020.

Biogen stock added approximately $20 billion in value as a result of this news.

Full data are expected at the CTAD meeting in December.

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October 11, 2019

Impact: High

  • Merck has announced that the China NMPA (National Medical Products Administration) has approved the use of Keytruda (pembrolizumab) as a frontline monotherapy agent in patients with locally advanced or metastatic NSCLC tumors with PD-L1 expression of at least 1% (TPS ≥1%, determined by an NMPA-approved test), without EGFR or ALK genomic mutations.
  • The approval is based on data from Chinese patients in the global Phase 3 KEYNOTE-042 trial (NCT02220894) and a separate China extension study (NCT03850444).
  • Patients with PD-L1 expression ≥1% treated with Keytruda (n=128) vs. platinum-based chemotherapy (n=134) showed mOS = 20.0 months vs. 13.7 months.
  • Results from the China extension study were presented at the IASLC World Conference on Lung Cancer in September 2019 (abstract MA11.02).

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October 1, 2019

Impact: High

  • Merck and Eisai have announced that FDA has granted an accelerated approval to the combination treatment of Keytruda/Lenvima (pembrolizumab/lenvatinib) for patients with advanced endometrial carcinoma that is not MSI-H (microsatellite instability-high) or dMMR (mismatch repair deficient), who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation.
  • This accelerated approval is based on ORR and duration of response data from the Phase 2 KEYNOTE-146 trial (NCT02501096).
    • ORR = 38.3% (CR rate = 10.6%)
    • mDoR (median duration of response) = not reached (1.2+ to 33.1+ months)
    • % with duration of response ≥ 6 months = 69%
  • This accelerated approval was reviewed under FDA’s Real-Time Oncology Review (RTOR) pilot program (submission on June 17, 2019; accelerated approval on September 17, 2019).
  • Additionally, this review was conducted under Project Orbis. Project Orbis allows for a concurrent review process from multiple international regulatory agencies. For this approval, FDA, Australian Therapeutic Goods Administration (TGA) and Health Canada collaboratively reviewed the submission and made a simultaneous decision in all 3 countries.

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October 1, 2019

Impact: High

  • The CHMP adopted a positive opinion recommending a change in the MAA for Remsima to include a new route of administration, new strength, and new pharmaceutical form:
  • Remsima 120 mg solution for subQ injection using prefilled pens or syringes.
  • It is only authorized in the RA indication.

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September 25, 2019

Impact: High

Ardelyx received FDA approval for tenapanor for the treatment of IBS-C in adults. The approval was based on two phase 3 clinical trials, T3MPO 1 and T3MPO2. The brand name for the drug will be Ibsrela. The label contains a black box warning on the risk of serious dehydration in pediatric patients, which is due to a class effect of NHE3 sodium transport inhibitors.

Ardelyx has decided not to commercialize the drug for IBS-C indication themselves and is awaiting a commercial partner who would also be interested in developing the drug for CIC. The company did not disclose details of ongoing partnership conversations during the call following tenapanor’s approval. Read more

September 4, 2019

Impact: High

  • GSK has announced that the pivotal phase 2 DREAMM-2 trial (NCT03525678) of belantamab mafodotin has met the primary endpoint of ORR.
  • 196 relapsed multiple myeloma patients who were refractory to an immunomodulatory drug, a PI and an anti-CD38 antibody were enrolled.
  • Safety and tolerability are reportedly consistent with what was observed in the DREAMM-1 trial.
  • Data will be submitted for presentation at an upcoming scientific meeting and be used to support regulatory filings later this year.

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