NVAX – RSV Vaccine Dose Confirmatory Trial Highly Successful – After the close, Novavax announced positive top-line safety and immunogenicity data from its RSV-F protein nanoparticle vaccine candidate in a Phase 2 clinical trial in 720 women of childbearing age. The randomized, blinded, placebo-controlled Phase 2 study was designed to evaluate the immunogenicity and safety of multiple formulations of Novavax’ RSV-F protein nanoparticle vaccine adjuvanted with aluminum phosphate. The primary outcome of the trial was safety and immune response, measured by levels of serum IgG antibody specific for the F protein. Participants received either one or two intramuscular injections featuring two different dose levels of vaccine antigen with a range of doses of aluminum phosphate adjuvant. These top-line data over the 91-day period following first immunization were highly successful for safety and efficacy and support Novavax’ maternal immunization strategy. With four positive studies in more than 1,100 safety subjects, the current trial represents a major step forward and another de-risking event. Reiterate our BUY under 6 and 13 TARGET PRICE.
Highlights of the interim results include the following:
- The RSV-F vaccine candidate was well tolerated, with no vaccine-related serious adverse events, at all doses and formulations. The safety profile was consistent with data from prior Phase 1 and 2 studies.
- Significant increases in RSV-F antibody levels were observed across all doses and formulations, consistent with prior studies. Peak RSV-F antibody levels were observed in the group that received a single dose of vaccine containing 120 µg of antigen with one-third of the aluminum phosphate dose used in prior studies.
- Clear increases in RSV neutralizing antibodies were also shown across all doses and formulations, and were strongest in women entering the study with the lowest baseline levels, in confirmation of prior studies.
- Vaccine-induced palivizumab-like antibody levels demonstrated strong concordance with anti-RSV-F antibody responses. A single 120 µg antigen dose generated peak palivizumab-like antibody levels of approximately 400 µg/mL, the highest levels seen in any study.
- Kinetic analysis of the antibody responses showed rapid increases in antibody levels in all vaccine formulations and dosing regimens. A single 120µg antigen dose generated peak RSV-F and palivizumab-like antibody levels within 14 days of immunization, and high levels of both were sustained through the 91-day observation period.
In our view, the consistency across doses/formulations and compared with previous studies is impressive. The NVAX F-protein vaccine delivered improved immunogenicity in a one-dose regimen, likely leading to improved patient convenience, vaccine uptake and compliance, thus decreasing the burden of RSV disease. In addition the single dose should lead to flexibility for administration during pregnancy. The study confirms a previous clinical trial in women of childbearing age from 2013. These data support the first maternal immunization trial, currently projected to begin in Q4:14.
The Company has requested a Type C meeting with the FDA this summer to discuss the entire suite of pre-clinical and clinical data in support of the initiation of studies in pregnant women. A Type C meeting will allow the company to decide on multiple aspects of the next clinical trial(s). Now they appear to have the appropriate dose/formulation for registration trials – it will be interesting to note if the FDA allows a randomized trial designed for Phase II, but possibly with a crossover to a Phase III study. The impressive results reported today, in our view, makes us believe the path to market could be accelerated. Novavax expects to present the entire date-set at an appropriate scientific forum in the future.
While the most important trials are still ahead of them (e.g., in pregnant women to observe placental transfer of protection, combination trials with the NVAX quadrivalent flu vaccine), today’s results could not be any better. The path to NVAX developing a truly disruptive “respiratory vaccine” has just taken a major step forward.