AnaptysBio has unveiled positive findings from its Phase 2b RENOIR clinical trial evaluating rosnilimab. Nearly 70% of participants achieved low disease activity (CDAI ≤10) by Week 14, with improvements persisting through Week 28. The investigational therapy met its primary endpoint by delivering statistically significant gains in DAS28‑CRP scores at Week 12 compared to placebo, alongside robust secondary outcomes, including high ACR50/70 response rates. Notably, rosnilimab’s safety profile was on par with placebo, with no increase in serious adverse events. Full data are slated for release in Q2 2025, and AnaptysBio aims to extend this novel immunological approach to other inflammatory conditions such as ulcerative colitis (UC). In an exclusive Q&A, Dr. Paul F. Lizzul, the company’s Chief Medical Officer, offered deeper insights into these results and their clinical implications.
What do you consider the most compelling aspect of rosnilimab’s Phase 2b data in RA, given that nearly 70% of treated patients reached low disease activity (CDAI ≤10) by Week 14?
Lizzul: Rheumatoid arthritis (RA) is an autoimmune disease that causes joint inflammation and pain that significantly impacts people’s daily lives. As a clinician, it’s encouraging that more than 70% of trial participants report feeling substantially better, with a 20% reduction in disease activity (ACR20) already by Week 12. This is important because around 12 weeks into treatment, treating physicians typically make decisions about continuing or changing therapy for their patients.
In addition, it is even more encouraging and compelling to see the continued momentum and improvement week by week and to achieve an important indicator of substantial efficacy, noted as low disease activity (LDA) by Week 14. The achievement of CDAI LDA is a validated threshold that correlates with slowing the progression of joint erosion and physicians often seek to achieve this meaningful outcome by six months.
And since we are talking about a novel approach to treating RA, it’s also great to see robust translational and pharmacological activity – there is a rapid and sustained ~90% reduction in PD-1high T cells (the disease-driving immune cells), leading to favorable T cell composition and restored immune homeostasis. We also observed a ~50% reduction in C-reactive protein, or CRP, a well-established objective marker of inflammation.
These combined clinical and translational data to date further validate our scientific approach to target the PD-1 co-inhibitory receptor on activated immune cells in RA, and boost our confidence in targeting other heterogeneous, systemic autoimmune and inflammatory diseases, including ulcerative colitis (UC), that might benefit from this novel approach targeting a central node of inflammation.
How do the robust secondary endpoints (ACR20/50/70 responses) observed in the trial compare with those seen in existing RA treatments, and what clinical benefits might this offer patients?
Lizzul: ACR50/70 response endpoints measure the changes in RA disease activity. For example, an ACR50 response score requires a 50% reduction in the number of swollen and tender joints and a 50% reduction in three of the following measures: physician or patient global assessment, pain assessment, CRP or erythrocyte sedimentation rate and health assessment questionnaire score. Higher responses indicate better clinical benefits.
Rosnilimab’s ACR50 and ACR70 responses at Week 14 are very promising compared to existing RA treatments, showing response rates at Week 14 that are similar to those seen in other medications at Week 24. Additionally, data suggest that maximal efficacy may not yet be reached and could improve over time, potentially delivering broader benefit for a broader range of patients. For example, the 69% of patients achieved CDAI LDA at Week 14 appear to show sustained ACR50 responses and potentially deepening ACR70 responses.
What matters in clinical practice and for patients is driving to these deep, durable and safe responses.
The safety profile of rosnilimab appears to be very similar to placebo, with very low rates of serious adverse events. How might this impact its positioning relative to established therapies that carry significant safety warnings?
Lizzul: Yes, that is certainly another very important and compelling outcome that we are quite pleased to observe at this time. At Week 12, we observed no serious adverse events associated with rosnilimab compared to participants on placebo, no elevation in serious infections, no malignancies and no major adverse cardiac events (MACE) in participants on rosnilimab. Headaches and upper respiratory infections were the most common adverse events reported in the study overall across all patients. And as of the Dec. 10 data cut off, this encouraging profile remains consistent for the trial participants who have progressed further out in time on treatment up to Week 28.
We look forward to reporting the full data in the second quarter of 2025 to further understand this promising safety and tolerability profile.
Given the observed rapid and sustained reduction in PD‑1high T cells, how does rosnilimab’s mechanism of action translate into potential clinical benefits for RA patients?
Lizzul: Rosnilimab directly targets PD-1, a co-inhibitory receptor preferentially expressed on the surface of activated T cells, which broadly impacts the pathogenic drivers of inflammatory diseases such as RA. Rosnilimab is designed to deplete (remove) PD-1high T cells and agonize the remaining PD-1+ T cells to restore immune homeostasis. In healthy patients, less than 15% of T cells are PD-1+ overall and an estimated 3-4% of T cells in the periphery are PD-1high expressing cells. In RA patients, there are twice the number of PD-1high T cells in the periphery and 80% of T cells in synovium are PD-1+ (with half PD-1high expressing cells).
The Phase 2b data show that rosnilimab depletes 90% of the PD-1high T cells in the periphery and reduces the overall number of T cells that are PD-1+ by 60%, bringing the immune system back into homeostasis. We also observed a ~50% reduction in CRP. These two immunological outcomes support that overall inflammation is decreasing in patients and that rosnilimab is performing as expected based on its targeted mechanism of action. Upcoming additional translational data will provide further insights into the potential clinical benefits of rosnilimab.
How might the nearly equivalent efficacy in both bio‑naïve and bio‑experienced populations influence the design of future Phase 3 trials for rosnilimab?
As expected, we observed generally higher overall efficacy in bio-naïve patients on rosnilimab than in bio-experienced patients at Week 14, but results were statistically significant for both arms and safety and tolerability trends were similar, with a very low trial discontinuation rate across both populations. This is promising as it suggests that rosnilimab has the practical potential to not only treat patients earlier in their disease course but also treat those who have cycled through many other RA therapies. Put another way, if the promising combined safety and efficacy profile continues to hold up in further development, rosnilimab could be used by physicians as a first line treatment and for more advanced, severe later stage rheumatoid patients.
We have been conducting internal discussions regarding Phase 3 trial designs, and the comprehensive clinical and translational data will help to further inform and support these designs. We look forward to presenting these additional efficacy and safety data and meeting with regulatory officials to discuss potential Phase 3 trial design.
With up to 25% of RA patients not reaching therapeutic goals with current medications, how might rosnilimab’s early efficacy and safety profile address these unmet needs?
Yes, one in four people living with RA do not experience the relief they desire with current treatments. The positive and statistically significant Phase 2b results for rosnilimab in RA potentially pave the way for a differentiated, novel treatment option for people with RA who have not had the benefit of a new therapeutic class in more than a decade.
Notably, trial participants responding to rosnilimab also demonstrated sustained LDA responses, specifically CDAI LDA and ACR50, with indications of further improvement in ACR70 out to six months and potentially beyond.
We are highly encouraged by these trial results for rosnilimab and the potential impact it may have on the lives of patients managing RA.
The presentation hints at rosnilimab’s potential in ulcerative colitis (UC). How might the translational and clinical findings in RA inform its development strategy for other inflammatory conditions like UC?
These rosnilimab Phase 2b data from RA patients further boost our excitement and confidence in succeeding in our ongoing Phase 2 ulcerative colitis trial for three reasons:
First, rosnilimab’s safety and tolerability profile to date satisfies the expectations needed for a therapy to be prescribed in moderate and severe UC patients.
Second, multiple drug classes are approved in both RA and UC, such as the JAKs and TNFs, with consistent efficacy results. As a reminder, there is strong overlapping biology in these two diseases that is relevant for rosnilimab’s targeted mechanism of action.
And third, the translational data suggest that depletion matters. We’ve shown that rosnilimab significantly reduces pathogenic T cells in the periphery. A return to low numbers of T (PD-1high) cells is correlated with clinical remission of UC. Also, rosnilimab reduced CRP levels by approximately 50%, which is associated with a reduction of inflammation beyond only T cells.
These initial findings bode well for the anticipated top-line UC results, now anticipated in Q4 2025.
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