A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Oral Doses of V-7404 in Healthy Adult Volunteers.

V-7404, a direct-acting enterovirus (EV) 3C protease inhibitor, is being developed as a treatment option for serious EV infections, including infections in immunodeficient people excreting vaccine-derived polioviruses. V-7404 may be combined with pocapavir (V-073), a capsid inhibitor, to treat these infections. A phase 1 single ascending dose (SAD;  = 36) and multiple ascending dose (MAD;  = 40) study was conducted to assess the safety, tolerability, and pharmacokinetics (PK) of V-7404 in healthy adult volunteers following oral doses starting at 200 mg and escalating to 2,000 mg once daily (QD) and 2,000 mg twice daily (BID).

Clearance of Immunodeficiency-associated Vaccine-derived Poliovirus Infection With Pocapavir.

Pocapavir exhibits antiviral activity against both polio and nonpolio enteroviruses. There is limited experience of the use of this investigational drug in young children with enteroviral infection. We describe the successful clearance of prolonged immunodeficiency-associated vaccine-derived type 3 poliovirus infection by pocapavir in an infant with underlying X-linked agammaglobulinemia.

Antiviral Activity of Pocapavir in a Randomized, Blinded, Placebo-Controlled Human Oral Poliovirus Vaccine Challenge Model.

Background: Immunodeficient individuals who excrete vaccine-derived polioviruses threaten polio eradication. Antivirals address this threat.

Methods: In a randomized, blinded, placebo-controlled study, adults were challenged with monovalent oral poliovirus type 1 vaccine (mOPV1) and subsequently treated with capsid inhibitor pocapavir or placebo.

Progress in the development of poliovirus antiviral agents and their essential role in reducing risks that threaten eradication.

Chronic prolonged excretion of vaccine-derived polioviruses by immunodeficient persons (iVDPV) presents a personal risk of poliomyelitis to the patient as well as a programmatic risk of delayed global eradication. Poliovirus antiviral drugs offer the only mitigation of these risks. Antiviral agents may also have a potential role in the management of accidental exposures and in certain outbreak scenarios.