Pfizer's CD47 Setback: A Warning Sign for Biotech Investors in a Risky Oncology Landscape

The recent termination of Pfizer's Phase II trial for its CD47-targeting drug maplirpacept—due to enrollment failures—marks a critical turning point in the CD47 therapeutic space. With only six patients enrolled in its diffuse large B-cell lymphoma (DLBCL) trial, Pfizer has acknowledged a stark operational reality: developing single-agent CD47 inhibitors for rare cancers is a high-risk, low-reward proposition. This setback, combined with industry-wide failures in the CD47 class, underscores the need for investors to reassess exposure to single-mechanism oncology assets and prioritize companies with adaptive strategies or diversified pipelines.

The CD47 Pipeline Crisis Deepens

Pfizer's discontinuation of the DLBCL trial (C4971003) in June 2025, just two years after it began, signals a growing reckoning for CD47 inhibitors. The trial's collapse wasn't due to safety or efficacy issues but rather an inability to recruit enough patients—a recurring challenge in rare cancer trials. This failure is particularly notable given Pfizer's $2.26 billion acquisition of Trillium Therapeutics in 2021, which brought maplirpacept into its portfolio.

But Pfizer isn't alone. Across the industry:
- Gilead's magrolimab, a CD47 inhibitor approved for acute myeloid leukemia, was terminated in advanced-stage trials after showing increased mortality in combination therapies.
- ALX Oncology's evorpacept failed mid-stage trials in head and neck cancers, with safety concerns and lackluster efficacy data.
- AbbVie's crovalimab also faced setbacks, including delays in its myeloma trials.

The common thread? CD47 inhibitors' narrow therapeutic windows, unpredictable safety profiles, and the logistical nightmare of recruiting patients for rare indications.

Pfizer's stock has held steady, but peers like Gilead and ALXN have seen declines amid CD47 setbacks.

Why Recruitment and Safety Issues Matter

The operational risks here are systemic:
1. Patient Accessibility: Rare cancers like DLBCL often lack large patient pools, making recruitment a logistical and financial burden.
2. Biomarker Uncertainty: CD47's role in cancer remains poorly understood. Without reliable biomarkers to identify responsive patients, trials risk being underpowered.
3. Toxicity Risks: CD47 inhibitors can cause severe anemia and thrombocytopenia, complicating combination therapies and limiting dosing flexibility.

These factors create a “perfect storm” for single-agent CD47 programs. As Pfizer shifts focus to combination trials—e.g., pairing maplirpacept with Roche's glofitamab—the company is hedging its bets. But such moves highlight the fragility of CD47 as a standalone target.

Implications for Investors: Time to Diversify

The writing is on the wall: investors should avoid late-stage CD47 assets and pivot to companies with:
- Adaptive Trial Designs: Firms like AstraZeneca (AZN) and Merck (MRK) use biomarker-driven strategies and basket trials to mitigate recruitment risks.
- Multi-Mechanism Approaches: Biotechs like ImmunoGen (IMGN) and Turning Point Therapeutics (TPTX) are advancing antibody-drug conjugates and combination therapies that target multiple pathways.
- Diversified Oncology Pipelines: Companies such as J&J (JNJ) and BMS (BMY) spread risk across solid tumors, blood cancers, and immuno-oncology.

Portfolio Adjustments: Where to Allocate Capital

1. Divest from CD47-Centric Firms: Sell stakes in companies with single-mechanism CD47 pipelines (e.g., ALX Oncology) unless they demonstrate clear pathways to combination therapies or biomarker validation.
2. Favor Adaptive Strategies: Back companies using “platform” approaches, such as Incyte (INCY) or Exelixis (EXEL), which leverage genomic data to refine trial designs.
3. Prioritize Safety-First Innovation: Focus on therapies with strong preclinical safety data, like Epizyme's (EPZM) epigenetic drugs or Arvinas' (ARVN) targeted protein degraders.

Conclusion

Pfizer's CD47 stumble is a symptom of a broader industry problem: the high-risk, high-reward nature of oncology drug development. Investors must recognize that single-agent CD47 programs face insurmountable hurdles in recruitment, safety, and biomarker clarity. Instead, capital should flow toward companies with adaptive trial strategies, multi-target oncology platforms, and therapies that reduce reliance on fragile single-mechanism hypotheses.

In short: avoid CD47's dead ends and invest in the innovators who are rewriting the rules of cancer treatment—one adaptive trial at a time.

This article reflects analysis as of June 19, 2025. Always consult with a financial advisor before making investment decisions.