FDA denies Rigel's COVID-19 hopeful Tavalisse for hospitalized patients, asks for late-stage data

The FDA has authorized a few of drugs for emergency use in hospitalized COVID-19 patients, but Rigel Pharmaceuticals’ autoimmune disease drug Tavalisse won’t be joining the group right now.

The FDA has told Rigel that Tavalisse, an oral spleen tyrosine kinase (SKY) inhibitor, won’t get an emergency use authorization (EUA) just yet. The reason? The drug’s existing COVID-19 data, from a phase 2 trial in just 59 patients, are not enough, Rigel said Friday.

Rigel is running a larger phase 3 trial that’s actively enrolling patients. If that trial hits its goals, the company plans to resubmit the EUA application with more data, Rigel president and CEO Paul Rodriguez said in a statement.

The phase 3 trial plans to enroll 308 hospitalized COVID-19 patients who will receive either Tavalisse (fostamatinib) plus standard or care or placebo plus standard treatment. The study excludes the most severe patients who need extracorporeal membrane oxygenation. As of Thursday, the trial had recruited 176 patients, and Rigel expects enrollment to finish by the end of the year.

The study aims to find out if the Rigel drug can reduce the risk of progression to severe or critical disease within 29 days among a group of patients without respiratory failure but who are at a high risk of advancing to severe stages of COVID-19.

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Severe COVID-19 patients can experience acute respiratory distress syndrome as a result of an overreactive immune response against the infection. Because SYK is involved in the signaling pathways of many immune cells, its inhibition by fostamatinib could reduce the release of pro-inflammatory cytokines, Rigel figures. The drug is already FDA-approved and sold under the brand Tavalisse to treat chronic immune thrombocytopenia, a rare autoimmune disease where the body’s own immune system mistakenly attacks platelets in the blood.

In a small phase 2 trial run by the National Heart, Lung, and Blood Institute (NHLBI), investigators found fostamatinib to be well tolerated in hospitalized patients who required some form of oxygen support. What’s more, the trial also found some encouraging efficacy signs for fostamatinib. Among the 30 patients on fostamatinib, zero died at day 29 compared with three in the 29-patient placebo group. The Rigel drug also helped patients come off ventilation and improve faster in clinical status, the company said in April.

Besides the Rigel-sponsored phase 3 trial, the NHLBI is also including fostamatinib as one treatment arm in the ACTIV-4 phase 3 trial. The study adopts an adaptive trial design that allows for the stopping and adding of new therapies based on their performance. The trial covers patients already on oxygen therapy and evaluates the oxygen-free days through day 28 for each treatment arm, as well as death rate, clinical status and use of invasive ventilation.

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Very few drugs have the FDA’s stamp of consent to treat hospitalized COVID-19 patients. Available options include Gilead Sciences’ antiviral drug Veklury. From the anti-inflammatory side, Roche’s IL-6 inhibitor Actemra and Eli Lilly’s JAK inhibitor Olumiant are authorized for emergency use to treat hospitalized patients requiring oxygen support. In addition, low-cost corticosteroids are also widely used to reduce inflammation in hospitalized patients.

Humanigen also awaits an FDA decision for an EUA application of lenzilumab to treat hospitalized COVID-19 patients. The GM-CSF inhibitor showed in a phase 3 trial that it could improve the likelihood of survival without ventilation by 54% over placebo in hospitalized patients.

Several anti-SARS-CoV-2 antibody drugs also boast EUAs for COVID but for outpatients who are at risk of progressing to hospitalization or more serious disease.