Candidate: Itolizumab

Category: ANTIBODY

Type: First-in-class immune-modulating antibody therapeutic designed to inhibit CD6, in order to reduce the activation and trafficking of pathogenic T cells that release pro-inflammatory cytokines in a range of autoimmune and inflammatory diseases.

Status: Equillium said November 25 that it would not launch as planned the Phase III EQUINOX trial (NCT04605926), designed to evaluate itolizumab in hospitalized COVID-19 patients suffering from acute respiratory distress syndrome (ARDS), “due to the rapidly evolving COVID-19 treatment landscape.” Instead, citing positive interim clinical data in the indication, Equillium CEO Bruce Steel said the company would instead prioritize its R&D of itolizumab in acute graft-versus-host disease, as well as advancing studies of itolizumab in lupus / lupus nephritis (Phase Ib EQUALISE trial, actively enrolling) and uncontrolled asthma (Phase Ib EQUIP trial, actively enrolling).

Equillium said October 29 that it planned to start enrolling patients during the fourth quarter of 2020, with initial clinical data expected by mid-year 2021, soon after receiving a Study May Proceed letter from the FDA allowing the trial to proceed.

The EQUINOX trial was designed to enroll a total of 800 patients at sites in and outside the U.S., with interim assessments at 20% and 50% of enrollment. Patients enrolled in the trial were to be randomized 1:1 to receive either itolizumab or placebo in addition to best supportive care for the treatment of COVID-19. Patients were to receive up to two doses of study drug (itolizumab or placebo) at Day 1 and Day 8 (if needed) and be monitored through Day 28 while hospitalized or through post-discharge follow-up.

The primary endpoint of EQUINOX was to evaluate the benefit of itolizumab on recovery in patients hospitalized with COVID-19. Key secondary endpoints include mortality benefit and other measures of clinical improvement. The trial will also evaluate the safety, tolerability and pharmacokinetics (PK) of itolizumab.

Equillium said the FDA had indicated to the company that if EQUINOX met its primary and key secondary endpoints, the trial may have been sufficient to support regulatory filing of a BLA.

Also in October, Equillium’s development partner for itolizumab Biocon launched a 300-patient Phase IV trial with the drug—marketed there as ALZUMAb™—to treat COVID-19 patients in India to generate a larger body of scientific evidence to support the safety, efficacy and usefulness of itolizumab to treat COVID-19 patients.

Equillium said July 13 it plans to submit an IND to the FDA for a global randomized controlled clinical trial of itolizumab in COVID-19 patients. Those plans follow positive clinical results for itolizumab in an Indian trial, and the Drugs Controller General of India (DCGI) granting restricted emergency use of itolizumab for the treatment of cytokine release syndrome (CRS) in COVID-19 patients with moderate to severe acute respiratory distress syndrome (ARDS) in India.

Biocon reported results from a randomized, controlled, open-label study at four hospitals in India, enrolling a total of 30 hospitalized COVID-19 patients with moderate to severe ARDS. According to Biocon, the study’s 20-patient itolizumab arm showed no deaths and the recovery of all patients, compared to three deaths in the 10-patient control arm of best supportive care; the other seven patients recovered. Without disclosing numbers, Biocon said the mortality benefit seen in the itolizumab arm was statistically significant and that itolizumab patients also experienced significant reductions in inflammatory cytokines such as IL-6 and TNFα.

“These reported early clinical data suggest that itolizumab holds promise,” said Siddhartha Mukherjee, MD, PhD, a clinical advisor to Equillium and Biocon, a Pulitzer Prize Award-winning author, and an associate professor of medicine at Columbia University’s Herbert Irving Comprehensive Cancer Center.

Added Equillium co-founder and CEO Bruce Steel: “We are working with Biocon to review its full dataset with the goal to move swiftly in determining appropriate next steps to accelerate further development of itolizumab to treat moderate to severely ill COVID-19 patients in the U.S. and abroad in the face of this global crisis.”

Equillium has acquired rights to develop and commercialize itolizumab in the U.S., Canada, Australia, and New Zealand through an exclusive collaboration and license agreement with Biocon. In addition to COVID-19, Equillium is also evaluating itolizumab for the treatment of acute graft-versus-host disease and lupus nephritis under two open U.S. INDs, as well as conducting a clinical study in uncontrolled asthma in Australia and New Zealand.

Biocon has developed and won approval of itolizumab for the treatment of plaque psoriasis in India. Biocon manufactures itolizumab at commercial scale at its cGMP bio-manufacturing facility, which is regulated by the FDA.


COVID-19: 300 Candidates and Counting

To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:

FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.

DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data

KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.

TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.

GEN has also tagged the most common treatment types:

● ANTIVIRAL
● VAX
● ANTIBODY
● RNA