Monoclonal Antibody Shows 84% Relative Risk Reduction of Symptomatic COVID-19 Vs Placebo

Image credit: Invivyd

Invivyd recently announced its phase 3 CANOPY trial evaluating monoclonal antibody, pemivibart (Pemgarda) against COVID-19 had been published in the journal Clinical Infectious Diseases.

Pemivibart showed a 84% relative risk reduction of symptomatic COVID-19 vs. placebo during the 6-month on-drug period, and 74% relative risk reduction sustained through a 6-month off-drug follow-up, highlighting durable protection even at low residual drug levels.

And in an evolving regulatory environment, Invivyd’s CANOPY results suggest a potential shift in how monoclonal antibody therapies might be considered for infectious disease prevention.

One of the patient groups being studied in the CANOPY trial is the immunocompromised. This group has had limited efficacy in terms of COVID-19 vaccine protection, so there is a need for additional immunization, especially in a patient base with major medical issues and can be at a higher risk for severe disease including hospitalization and mortality.

Contagion sat down to speak with Cameron Wolfe, MBBS, Duke University School of Medicine, principal Investigator for the trial, and Mark Wingertzahn, PhD, senior vice president of Clinical Development and Medical Affairs, Invivyd, to discuss the results of the trial.

Contagion: I wanted to begin by discussing the relative risk reduction. Can you elaborate on the significance of the 84% risk reduction observed during the 6-month on-drug period in the CANOPY trial?

Wingertzahn: The CANOPY study was unique in several ways. We had a placebo-controlled cohort where an 84% relative risk reduction was observed after two study drug doses—that corresponds to the 6-month time point. There was also an off-drug period, or what we might think of as a washout period, which continued from month six through month twelve.

That 84% relative risk reduction observed in the immunocompetent cohort offered a couple of key insights. First, it demonstrated that there are still highly effective and well-tolerated options beyond vaccines. Second, it showed a significant level of protection, particularly important given that this is the only monoclonal antibody currently available that has retained efficacy even after the emergence of Omicron.

So, we’re looking at a very contemporary drug evaluated in a modern patient population—really the only study done to date with a monoclonal antibody that still retains activity. The results demonstrated robust protection against a composite endpoint of RT-PCR confirmed COVID-19 cases, hospitalization, and death.

Contagion: An important component of this trial is that it included participants who are immunocompromised. Can you talk about the challenges this patient population faces with COVID-19 and any key takeaways for them from this study?

Wingertzahn: As I was preparing for this interview, I reflected on how I personally felt during the height of COVID. I was living in a high-rise in downtown Boston at the time, and I remember how empty and eerie the streets were — barely anyone was out. It felt isolating, unsettling, and frightening.

I think many of us with intact immune systems have since forgotten those feelings. But for immunocompromised individuals, that sense of isolation still persists. They still can’t safely enter crowded spaces like grocery stores, concerts, or malls. They continue to live in a very insular and cautious way.

They have to think carefully about when and how they can see family—whether it has to be outside rather than indoors, for instance. Unlike those of us with fully functioning immune systems, immunocompromised patients still live with that heightened caution and risk, which impacts their quality of life and social connectedness.

Contagion: In looking at the antibody safety profile, can you offer some insights on it during this trial?

Wolfe: I am glad that post marketing, we haven't seen anything on the allergic and anaphylactic side. That's reassuring. And I think, frankly, would be more consistent with what we knew from monoclonals in lots of other spaces. I think that's reassuring. The patients in whom you use these are complex patients with lots of medical issues and lots of risk, and I think the safety profile when balanced against what you're trying to achieve with the drug, I think actually stands out really well.

Contagion: And how does the trial position this form of prevention as a viable option for PrEP?

Wolfe: We've learned a lot in the last 4 or 5 years about who's at risk, who responds well to vaccines, and who gets more severe COVID. And I think what this trial does is builds on experience with other monoclonals really to highlight an effort for people who are still getting severe COVID And who have not been able to mount a sufficient response. The fact that this product maintains efficacy against current variants is its other strength there.