Clinical Catch-Up: AbbVie and Genmab, Intra-Cellular, Sanofi and GSK

With literally dozens of clinical trial announcements last week, here’s a look at some of the more interesting ones.

Genmab and AbbVie announced data from the Phase II expansion cohort of their EPCORE NHL-1 trial of epcoritamab for large b-cell lymphoma (LBCL). The drug is an IgG1 bispecific antibody that simultaneously binds to CD3 on T cells and CD20 on B cells and induces T cell-mediated killing of CD20+ cells. The study demonstrated durable responses with an overall response rate (ORR) of 63% and a complete response rate (CR) of 39% in patients previously treated with at least two lines of systemic anti-lymphoma therapy. Also, patients naive to CAR T-cell therapy hit 69% ORR and 42% CR, and patients who had received CAR T before had a 54% ORR and 34% CR.

Intra-Cellular Therapies presented data on its lumateperone (ITI-007) for the treatment of bipolar depression. The Phase III Study 404 met the primary endpoint for improvement in depression compared to placebo. Another analysis of the same study of the drug as a monotherapy for patients with Bipolar I or II disorder experiencing a major depressive episode hit both primary and key secondary endpoints, showing improvements in functional disability and quality of life. And yet another analysis of both the Study 404 and 401 compared the incidence of and shifts in metabolic syndrome with the drug alone in treating bipolar depression in patients with bipolar I and II disorder. The rates of metabolic syndrome were similar between the drug and placebo at baseline and remained stable at the end of treatment in both groups.

Sanofi and GlaxoSmithKline reported data from two clinical trials, VAT02 Cohort 2 and COVIBOOST VAT013, evaluating their next-generation COVID-19 booster vaccine. The vaccine candidate leverages a Beta variant antigen and GSK’s pandemic adjuvant. The Phase III VAT02 Cohort 2 study generated a significant increase in antibody titers above baseline 15 days after receiving the shot against multiple variants of concern in adults who previously received the mRNA COVID-19 vaccine (Pfizer-BioNTech and Moderna). It demonstrated a 40-fold increase against the original Omicron variant, BA.1. It also doubled the neutralizing antibodies against Omicron BA.1 and BA.2 compared to the D614, the original parent virus booster. The COVIBOOST study, given after the Pfizer-BioNTech shots, induced a higher immune response than the Pfizer-BioNTech booster or the Sanofi-GSK first-generation booster.

Freeline Therapeutics initiated dosing of the second cohort of its Phase I/II B-LIEVE trial of FLT180a in hemophilia B. FLT180a is an experimental gene therapy that leverages a potent, rationally designed AAVS3 capsid containing an expression cassette encoding a gain of function Padua variant of human Factor IX. The second cohort testing was launched based on the strength of cohort one data and the advice of an Independent Data Monitoring Committee. The patients will receive the same dose, 7.7e11 vg/kg and an optimized prophylactic immune management regimen used with cohort one. The first cohort was completed in April. The company expects to present initial data from the first cohort at the International Society on Thrombosis and Haemostasis (ISTH) Congress in London, U.K., in July.

Actinogen Medical announced plans for a Phase II trial of Xanamem in patients with Major Depressive Disorder (MDD). It also plans Part B of the Phase II trial of the drug for Alzheimer’s disease, including about 300 patients with early stages of AD, including patients with Mild Cognitive Impairment. Impaired attention and memory are common symptoms of MDD. The decision to continue into Phase II was due to positive results from Part A of its two-part XanaMIA dose-ranging trial, which confirmed the drug’s ability to rapidly enhance attention and working memory. The drug is being developed for Alzheimer’s disease and depression. Xanamem blocks excess production of cortisol inside brain cells by blocking the 11beta-HSD1 enzyme.

Immunic published data from its Phase II EMPhASIS trial of vidofludimus calcium (IMU-838) in patients with relapsing-remitting multiple sclerosis (RRMS). Vidofludimus calcium is a novel and second-generation selective dihydroorotate dehydrogenase (DHODH) inhibitor that doesn’t have the off-target effects on kinases other drugs in the same class have. This allows for a better safety and tolerability profile. Inhibiting DHODDH suppresses MRI brain lesions and MS disease activity. The study hit its primary and key secondary endpoints for suppressing the number of combined unique active MRI lesions. It was safe and well-tolerated compared to placebo, with no increased infections, effects on liver or blood cell laboratory results. There was a very low treatment-related discontinuation rate. The company has initiated enrollment in the Phase III ENSURE trial of the drug for relapsing MS (RMS).

Pfizer shared data from the Phase II/II EPIC-SR trial of Paxlovid (nirmatrelvir tablets and ritonavir tablets) in patients at standard risk for developing severe COVID-19. The earlier interim analysis had indicated that the novel primary endpoint of self-reported, sustained relief from all symptoms for four consecutive days was missed. A non-significant 70% relative risk reduction was seen in the key secondary endpoint of hospitalization or death. The updated data from 1,153 patients enrolled through December 2021 demonstrated a non-significant 51% relative risk reduction. A sub-group analysis of 721 people vaccinated against COVID-19 with at least one risk factor for severe COVID-19 showed a non-significant 57% relative risk reduction in hospitalization or death. Due to the extremely low rate of hospitalization or death seen in the standard-risk patient population, the company decided to halt enrollment into EPIC-SR and include the data in a planned New Drug Application (NDA) to the U.S. Food and Drug Administration to support authorization of the drug in high-risk individuals.

Kymera Therapeutics dosed the first patients in two separate Phase I trials of STAT3 degrader KT-333 and IRAKIMiD degrader KT-413. The KT-333 trial includes patients with relapsed/refractory liquid and solid tumors, including T cell lymphomas and leukemia. The KT-413 trial is focused on patients with r/r B cell lymphomas, including MYD88-mutant diffuse large B cell lymphoma (DLBCL). STAT3 is a transcriptional regulator long thought to be undruggable but linked to numerous other cancers and inflammatory and autoimmune diseases. KT-333 is designed to degrade the STAT3 protein. KT-413 degrades interleukin-1 receptor associated kinase 4 (IRAK4) and the immunomodulatory imide drug (IMiD) substrates Ikaros and Aiolos.

Addex Therapeutics terminated its Phase IIb/III trial of dipraglurant due to the slow recruitment of participants. The drug is being developed as a potential treatment for dyskinesia associated with Parkinson’s disease (PD-LID). Addex believes this is because of patient concerns over COVID-19, staffing shortages, and turnover within study sites. The company is based in Geneva, Switzerland. The company emphasized that the trial cancellation was not due to anything about the drug, which it believes has potential for this indication. But Addex doesn’t believe it is feasible to continue the study at such a slow recruitment rate and will plan to advance its preclinical portfolio toward the clinic and work on strategic collaboration.