Clinical Catch-Up: July 20-24

It was a busy week for clinical trial news, with some very important early-stage trial data for various COVID-19 vaccines. Here’s a look.

COVID-19-Related

Pfizer and BioNTech announced initial data from the German Phase I/II trial of BNT162b1, one of their mRNA vaccines against COVID-19. The companies indicate the preliminary data supported and expands on early results from the recently disclosed early data from the US trial of BNT162b1.

The vaccine produced high, dose level-dependent neutralizing antibodies against SARS-CoV-2 and RBD-binding IgG concentrations after the second date. The titers of neutralizing antibodies were comparable to a group of convalescent antibody titers from patients who recovered from COVID-19. They companies stated, “Furthermore, sera of vaccinated subjects displayed broadly neutralizing activity in pseudovirus neutralization assays across a panel of sixteen SARS-CoV-2 RBD variants represented in publicly available SARS-CoV-2 sequences and against the newly dominant D614G strain.”

Synairgen announced positive results from a clinical trial of its wholly-owned inhaled formulation of interferon beta in COVID-19 patients. The company indicated its nebulizer treatment resulted in a 79% lower risk of patients developing severe disease compared to those receiving a placebo. And the patients receiving the treatment “were more than twice as likely to recover (defined as ‘no limitation of activities’ or ‘no clinical or virological evidence of infection’) over the course of the treatment period compared to those receiving placebo.”

AstraZeneca and the University of Oxford published data from their COVID-19 vaccine candidate showing a seroconversion rate as high as 97% at day 28. All participants were from Wuhan, China. It also showed positive T cell responses of 96% and 97% in two different dose groups, 1x10¹¹ and 5x10¹⁰, respectively. Severe adverse reactions were reported in 9% in the 1x10¹¹ cohort and in one patient in the 5x10¹⁰ group. The reactions were fever, and all resolved within 72-96 hours.

CanSino Biologics, along with China’s military research unit, reported early data on its Phase II trial for its COVID-19 vaccine, Ad5-nCOV. The results in 508 patients showed antibody and T-cell immune responses. There were no reported serious side effects. The data was published in the journal The Lancet.

Cerecor enrolled the first patient in a proof-of-concept trial of anti-LIGHT monoclonal antibody, CERC-002, in patients with COVID-19 cytokine storm-induced ARDS. It will enroll about 82 patients hospitalized with COVID-19 ARDS. CERC-002 was licensed from Kyowa Kirin Co.

Arcturus Therapeutics, and Duke-NUS Medical School in Singapore, received approval by the Singapore Health Sciences Authority to proceed with a Phase I/II trial of its COVID-19 vaccine candidate, LUNAR-COV19. It will test the vaccine in up to 108 healthy adults.

Glenmark Pharmaceuticals announced topline results from its Phase III trial of favipiravir in mild to moderate COVID-19 at seven sites in India. Favipiravir is a broad spectrum oral antiviral drug that selectively inhibits RNA-dependent RNA polymerase and the viral replication phase of SARS-CoV-2.

Researcher in Brazil published a study in The New England Journal of Medicine finding that hydroxychloroquine, alone or with antibiotic azithromycin, did not help hospitalized patients with mild-to-moderate COVID-19. The study out of Brazil evaluated 667 patients, 504 who had confirmed COVID-19 and were included in a modified intention-to-treat analysis. It was conducted at 55 hospitals in Brazil. The hospitalized patients had either suspected or confirmed COVID-19 and were receiving either no supplemental oxygen or a maximum of four liters per minute of supplemental oxygen. The patients were randomized 1:1:1 to receive standard care, standard care plus hydroxychloroquine at 400 mg twice a day, or standard care plus hydroxychloroquine 400 mg twice a day plus azithromycin 500 mg once a day for seven days.

The primary endpoint was clinical status at 15 days assessed using a seven-point ordinal scale, with levels ranging from one to seven and higher scores indicating a worse condition. They also evaluated safety.

Non-Covid-19-Related

Amplyx Pharmaceuticals announced positive topline data from its Phase II trial of foxmanogepix as first-line treatment for Candida invasive fungal infections. The trial hit its primary efficacy endpoint, showing a treatment success rate of 80%. Fosmanogepix is a novel, broad-spectrum antifungal agent.

ACADIA Pharmaceuticals reported topline data from its Phase III CLARITY study of Nuplazid (pimavanserin) as adjunctive treatment for major depressive disorder (MDD). The study actually combined data from two identical studies. However, the study failed to hit statistical significance on the primary endpoint, which was the 17-item Hamilton Depression Rating Scale (HAMD-17) total score change from baseline to week 5.

Biogen plans to initiate a Phase IV trial, RESPOND, to study the clinical benefit and assess the safety of Spinraza (nusinersen) in infants and children with spinal muscular atrophy (SMA) who still have unmet clinical needs after treatment with gene therapy Novartis/AveXis’ Zolgensma (onasemnogene abeparvovec). Spinraza is the first therapy approved to treat infants, children and adults with SMA.

Aimmune Therapeutics published complete results from its pivotal Phase III European ARTEMIS trial of Palforzia (peanut (Arachis hypogaea) Allergan Powder-dnfp). The trial met all primary, secondary and safety endpoints, and showed that patients receiving it experienced a high degree of desensitization to peanut over nine months.

Biohaven Pharmaceutical completed enrollment in the M-STAR Phase III trial of verdiperstat in multiple system atrophy (MSA). Verdiperstat is a potential first-in-class myeloperoxidase (MPO) inhibitor that targets sources of neuroinflammation that contribute to brain cell death in neurodegenerative diseases including MSA and ALS.

CVRx completed enrollment in the BeAT-HF Phase III post-market phase of the trial. CVRx also enrolled the first patient in a heart failure registry designed to be a national repository of individual patient data from commercial Barostim Neo cases. Barostim Neo uses CVRx-patented technology to send electrical pulses to baroreceptors located in the wall of the carotid artery in order to deliver Barostim Therapy.

AbbVie announced that its Rinvoq (upadacitinib) as a monotherapy hit both primary and all secondary endpoints in the second Phase III trial, Measure Up 2, in patients with moderate to severe atopic dermatitis.

The co-primary endpoints were at least a 75% improvement in the Eczema Area Severity Index (EASI 75) from baseline and a validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1, clear or almost clear, at week 16. The study evaluated the efficacy and safety of two doses, 15 mg and 30 mg, once a day, compared to placebo in adolescents and adults with moderate to severe atopic dermatitis who are eligible for systemic therapy.

Akero Therapeutics published data from the Phase I trial of efruxifermin in non-alcoholic steatohepatitis (NASH). Efruxifermin is a fibroblast growth factor 21 analog. The data demonstrated the drugs potential to modulate biomarkers associated with metabolic diseases, including NASH.

XyloCor Therapeutics dosed the first two patients in the EXACT Trial, a Phase I/II dose escalation study of XC001 in refractory angina. The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) is testing the therapy at six months in patients who suffer from chronic angina caused by coronary artery disease with no other treatment options. It will enroll 12 patients.

Incyte announced data from the Phase III REACH3 trial of Jakafi (ruxolitinib) in patients with moderate or severe steroid-refractory or steroid dependent chronic graft-versus-host disease (GVHD). The drug hit the mark, meeting the trial’s primary endpoint of superior overall response rate (ORR) at Week 24 compared to best available therapy (BAT). It also met both key secondary endpoints, significantly improving failure-free survival (FFS) and patient-reported symptoms based on the modified Lee chronic GVHD symptom scale (mLSS).

CymaBay Therapeutics announced the FDA had lifted all clinical holds on seladelpar for all three IND applications for NASH, primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). All trials were halted on November 25, 2019 after atypical histologic findings with no clinical or laboratory correlates. Seladelpar is a potent, selective, orally active PPARδ agonist.

GENFIT is discontinuing its Phase III RESOLVE-IT trial of elafibranor for NASH and fibrosis after May’s interim data analysis failed to hit a predefined primary endpoint. After a detailed review, the company decided to stop work on NASH and refocus the drug for primary biliary cholangitis (PBC).

VistaGen Therapeutics announced results of a positive meeting with the FDA over Phase III development of PH94B for acute treatment of anxiety in adults with social anxiety disorder (SAD). They hit a consensus on key aspects of the pivotal trial. The drug is a rapid onset neurosteroid nasal spray.

Genentech provided detailed results from the Phase III Archway study of its Port Delivery System with ranibizumab (PDS) for neovascular or “wet” age-related macular degeneration (nAMD). The PDS is a permanent refillable eye implant about the size of a grain of rice that continuously released a customized formulation of ranbizumab into the eye over time. Ranibizumab is a VEGF inhibitor.