BARDA no longer funding immunomodulators as support for the therapeutic class to treat COVID-19 grows
A slew of therapies entered the clinic this week aimed at tamping down the immune system to treat excessive lung inflammation in COVID-19 patients, even as BARDA announced it would no longer fund the class of therapeutic.
According to BioCentury’s COVID-19 Resource Center, there are more than 100 immunomodulators and immunosuppressants in the clinic to treat COVID-19. New entries this week include therapies from Evelo Biosciences Inc. (NASDAQ:EVLO), Theravance Biopharma Inc. (NASDAQ:TBPH) and Fulcrum Therapeutics Inc. (NASDAQ:FULC).
HHS’s Biomedical Advanced Research and Development Authority updated its website early this month to reflect that it is no longer accepting funding proposals for immunomodulators to treat COVID-19, or therapeutics targeting lung repair for the disease. It did not give a reason for the change.
The about-face follows the U.K. approval of anti-inflammatory steroid dexamethasone, which reduced mortality by 35% in ventilated COVID-19 patients (see “Master Protocol Shows Survival Benefit”).
The change also comes as ACTIV -- a COVID-19 consortium that counts BARDA’s parent agency as one of its members -- readies to launch a master protocol of immunomodulators this month.
The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) consortium is led by NIH and managed by the Foundation for NIH. Its members include 18 biopharma companies, FDA, CDC and the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR). BARDA is part of ASPR (see “ACTIV Coming into Focus”).
ACTIV is planning five master protocol trials, the first of which will test three host-targeted immune modulators against TNFα, CTLA-4 and CCR2/CCR5.
The Phase III ACTIV 1 trial will enroll about 2,000 patients over age 18 who have been hospitalized with a diagnosis of COVID-19. It’s slated to start in late June, and will be conducted by a CRO in the U.S., though it may be extended to other countries.
Cambridge starts platform trial
Another multitherapeutic COVID-19 trial with an immune focus was launched this week by Cambridge University.
The Phase II/III TACTIC-E trial will test unapproved therapies, as well as combinations of approved drugs, in patients hospitalized with COVID-19 that have risk factors.
The U.K. trial has announced two treatment arms: Evelo’s EDP1815, and a combo of Volibris ambrisentan and Forxiga dapagliflozin from AstraZeneca plc (LSE:AZN; NYSE:AZN)
Volibris, approved for pulmonary hypertension, is a selective endothelin A receptor antagonist; Type II diabetes treatment Forxiga inhibits SGLT2.
Evelo thinks EDP1815 can limit the production of inflammatory cytokines without the risks associated with immunosuppression. The microbe-based therapeutic is in a Phase Ib trial to treat psoriasis.
The biotech has also submitted an IND to FDA to start a Phase II trial of EDP1815 in New Jersey. It expects to start the study in July, with data due in 4Q20.
Additional therapies can be added to TACTIC-E, which plans to enroll up to 469 patients in the U.K. per arm. The trial may open in countries where infections remain high as numbers decline in the U.K.
The primary endpoint is reduction in the number of patients who develop severe complications of organ failure, ventilation or death.
More trial starts for immunomodulators
Fulcrum and Theravance also announced trial starts this week, with a third therapeutic from Palatin Technologies Inc. (NYSE-A:PTN) expected to enter the clinic in 4Q20.
Fulcrum said it’s been cleared by FDA to start a Phase III of losmapimod to treat higher risk adults hospitalized with COVID-19.
The biotech thinks its oral p38 MAPK inhibitor could act dually by both reducing the acute pro-inflammatory responses to SARS-CoV-2 infection, and restoring the antigen-specific T cell responses needed for viral clearance.
The placebo-controlled trial’s primary endpoint is proportion of patients who progress to death or respiratory failure by day 28.
Theravance dosed the first patient in a U.K. Phase II study of TD-0903 to treat hospitalized patients with acute lung injury from COVID-19.
The company previously tested the lung-selective, nebulized pan-JAK inhibitor in a Phase I study in healthy volunteers.
TD-0903 aims to block the release of cytokines and chemokines associated with acute lung injury and cytokine storm initiation, preventing progression to acute respiratory distress syndrome (ARDS).
Palatin said it plans to submit an IND next quarter for PL8177 to treat COVID-19, and start a Phase II trial 4Q20.
In preclinical models of inflammatory disease and lung injury, the MC1R agonist reduced inflammation, protected lung tissue and reduced lung fibrosis.
PL8177 has completed Phase I safety studies.
CCR2 (CD192) - CC chemokine receptor 2
CCR5 (CD195) - CC chemokine receptor 5
CTLA-4 (CTLA4; CD152) - Cytotoxic T-lymphocyte associated protein 4
MCD1R - Melanocortin 1 receptor
p38 MAPK (MAPK14) - p38 mitogen-activated protein kinase
SGLT2 - Sodium-glucose cotransporter 2
TNFα - Tumor necrosis factor alpha