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.

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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

June 23, 2020

Impact: Moderate

  • Researchers at the University of Oxford reported results from a randomized study of patients with severe cases of COVID-19, with either oral or intravenous administration of the widely available steroid dexamethasone, compared to usual care.
  • 2,104 patients were randomized to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4,321 patients randomized to usual care alone.
  • Dexamethasone reduced deaths by one-third in ventilated patients and by one fifth in other patients receiving oxygen only. There was no benefit among those patients who did not require respiratory support.
  • Full results have not yet been published or peer reviewed.
  • The RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial was established as a randomized clinical trial to test a range of potential treatments for COVID-19, including low-dose dexamethasone. Over 11,500 patients have been enrolled at over 175 NHS hospitals in the UK.

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June 23, 2020

Impact: High

  • Inventiva has released topline results from the phase 2b NATIVE trial of its pan-PPAR agonist, lanifibranor, for the treatment of NASH.
  • The primary endpoint of the trial, the Steatosis Activity Fibrosis (SAF) score at Week 24 was met, along with all other secondary outcomes at the same time point, including NASH resolution with no worsening of fibrosis and improvement of liver fibrosis with no worsening of NASH.
  • The proportion of patients achieving a reduction in SAF score of ≥2 at Week 24 was 41% and 49% in the lanifibranor 800mg and 1200mg treatment groups respectively, compared with 27% in the placebo group (p=0.061 and p=0.004).

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June 2, 2020

Impact: High

Gilead and Galapagos have announced positive topline results from the phase 2b/3 randomized, double-blind, placebo-controlled of the oral selective JAK1 inhibitor given once-daily. The results were particularly favorable for biologic-naive patients.

The study evaluated filgotinib 200mg, filgotinib 100mg and placebo in 1,348 biologic-naïve or biologic-experienced adult patients with moderate to severe active ulcerative colitis.

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June 2, 2020

Impact: High

During the virtual AAN 2020 conference, Biogen presented the baseline characteristics of participants in its phase 2 SPARK study of cinpanemab in PD. On May 20th, a month after the virtual conference, AAN opened its presentations to be viewed by the public without need for AAN registration, allowing us to view the slides on the SPARK study.

The study design for SPARK includes 3 treatment arms with cinpanemab doses of 250mg, 1250mg, and 3500mg. 357 patients are enrolled, split into two cohorts, the first consisting of 29 patients undergoing an intensive PK evaluation:

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May 7, 2020

Impact: Moderate

Cortexyme today announced the publication of research further documenting the ability of the pathogen Porphyromonas gingivalis to invade neurons and trigger Alzheimer’s-like neuropathology. This paper was published in the Journal of Alzheimer’s disease. Although P. Gingivalis is best known as a primary driver of chronic periodontal disease, it is also known that it can infiltrate the brain, where it can cause characteristics similar to AD. P. gingivalis breaks down proteins for its primary source of energy by utilizing toxic virulence factor proteases known as gingipains.

More than 90% of post-mortem brains of patients with AD showed a presence of gingipains. Further, in animal models, P. gingivalis results in brain infection and classic AD pathology. In this paper, Cortexyme proofs for the first time that P. gingivalis can indeed invade the human brain and can persist in mature human neurons expressing active gingipains and that these infected neurons show signs of AD-like neuropathology, such as synapse loss. Read more

May 7, 2020

Impact: Moderate

Supernus Pharmaceuticals announced that it will acquire the CNS portfolio of US WorldMeds, including Apokyn, Myobloc, and Xadago, as well as the phase 3 Apomorphine Infusion Pump, which is expected to be filed in 2H 2020. For Supernus, the acquisition aligns with its corporate strategy to diversify its product portfolio into PD and other movements disorders, building on its marketed products in epilepsy and pipeline in psychiatric disease. The acquisition expands Supernus’ commercial platform to include sales and marketing capabilities, which will work toward achieving potential peak sales of $100M-$175M for Apomorphine Infusion Pump.

An upfront cash payment of $300M will be made plus regulatory and commercial milestones up to $230M. The transaction is anticipated to close in 2Q 2020. Read more

March 24, 2020

Impact: Moderate

FDA has announced that it will postpone or cancel all non-essential meetings through April 30, 2020 due to COVID-19. The following meetings are affected:

  • April 21, 2020: FDA Pulmonary-Allergy Drugs AdCom to discuss Trelegy Ellipta sNDA for IMPACT trial results (GlaxoSmithKline).
  • April 22, 2020: FDA AdCom (undetermined) to discuss sNDA for OCA (Ocaliva) in liver fibrosis due to NASH (Intercept).
  • April 23, 2020: FDA imaging Drugs AdCom to discuss NDA for flortaucipir F18, radioactive diagnostic agent for Alzheimer’s disease (Ely Lilly).

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March 20, 2020

Impact: High

Regeneron and Sanofi have announced the initiation of a U.S. phase 2/3 trial evaluating anti-IL6 mAb Kevzara (sarilumab) in patients hospitalized with severe COVID-19 infection, to begin at medical centers in New York.

The adaptive design trial is expected to enroll up to 400 patients. The first part will evaluate the impact of Kevzara on fever and need for supplemental oxygen and the second part will evaluate the improvement in longer-term outcomes (preventing death, reducing the need for medical ventilation, supplemental oxygen and/or hospitalization).

Patients will be randomized 2:2:1 into Kevzara high dose, Kevzara low dose and placebo. The primary endpoint is reduction of fever and the secondary endpoint is decreased need for supplemental oxygen.

Trials outside the U.S. are expected to rapidly initiate, including in most affected areas such as Italy.

The restructuring of the Kevzara collaboration between the two companies is expected to be finalized in 1Q2020 as they continue to collaborate on COVID-19, with Regeneron leading U.S. work and Sanofi leading ex-U.S. work.

IL6 may play a role in driving the overactive inflammatory response in the lungs of COVID-19 patients and this is the first controlled U.S. trial to evaluate the effect of this cytokine inhibition.

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