Pfizer withdrawal of Oxbryta raises questions, sends Fulcrum stock higher

Pfizer (blue‘>PFE) announced that it is voluntarily withdrawing all lots of Oxbryta for the treatment of sickle cell disease as data shows risks outweigh its overall benefits in the approved population. Barclays believes the move will raise business development questions, while Leerink notes that although the financial impact of Oxbryta termination is modest, investors may also question GBT-601 prospects. Further, the latter firm says it expects minimal impact to Beam Therapeutics (BEAM), Bluebird Bio (BLUE), Editas Medicine (EDIT), and Crispr Therapeutics (CRSP), but believes the withdrawal could have a positive influence on the enrollment of Fulcrum Therapeutics’ (FULC) Phase 1b PIONEER trial.

WITHDRAWAL OF OXBRYTA: Pfizer announced that it is voluntarily withdrawing all lots of Oxbryta for the treatment of sickle cell disease at this time, in all markets where it is approved. Pfizer is also discontinuing all active voxelotor clinical trials and expanded access programs worldwide. Pfizer’s decision is based on the totality of clinical data that now indicates the overall benefit of Oxbryta no longer outweighs the risk in the approved sickle cell patient population.

The data suggest an imbalance in vaso-occlusive crises and fatal events which require further assessment. Pfizer has notified regulatory authorities about these findings and its decision to voluntarily withdraw OXBRYTA from the market and discontinue distribution and clinical studies while further reviewing the available data and investigating the findings. The company does not anticipate that this event will impact its full-year 2024 financial guidance.

QUESTIONS: Keeping an Equal Weight rating on Pfizer, Barclays says the voluntary withdrawal of sickle-cell therapy Oxbryta globally likely implies an imbalance in vaso-occlusive crises and/or fatal events to warrant the quick action. The firm notes the decision comes just shy of the two-year mark from Pfizer’s $5.4B acquisition of Global Blood Therapeutics to obtain Oxbryta and a follow-on sickle cell pipeline. The withdrawal will again raise questions on Pfizer’s business development effort, contends Barclays, arguing that it “adds a new example to old critiques.”

READTHROUGH: Also commenting on the news, Leerink notes that although the financial impact of Oxbryta termination is modest, investors may also question GBT-601 prospects. The firm awaits further clarity from Pfizer on whether GBT-601 will be impacted, and says it expects minimal impact to Market Perform-rated Beam Therapeutics, Market Perform-rated Bluebird Bio, Market Perform-rated Editas Medicine, and Outperform-rated Crispr Therapeutics, as target populations for Oxbryta and genetic medicines/transplantation have limited overlap. With two other novel agents approved – Emmaus Life Sciences’ (EMMA) Endari and Novartis’ (NVS) Adakveo, Leerink does not expect Oxbryta withdrawal to materially impact near-term patient demand for Crispr/Vertex Pharmaceuticals’ (VRTX) Casgevy or Bluebird Bio’s Lyfgenia.

Additionally, the firm thinks that the withdrawal of Oxbryta could have a positive influence on the enrollment of Fulcrum Therapeutics ‘ Phase 1b PIONEER trial, a hurdle that the company has been trying to overcome, getting them one step closer to reporting data in 2025. Recall, after providing several encouraging data cuts over the past two, the FDA placed a full clinical hold on pociredir due to non-clinical and clinical evidence of hematological malignancies observed with other inhibitors of polycomb repressive complex 2. The clinical hold has been lifted, and Fulcrum estimates that about 7.5K to 10K patients in the U.S. meet the inclusion and exclusion criteria of the amended protocol. Although pociredir cannot be studied on top of hydroxyurea unlike Oxbryta, Leerink believes that Oxbryta’s withdrawal could help foster the enrollment of PIONEER especially among patients who are on or have been on Oxbryta alone. The firm remains constructive on pociredir’s efficacy, but the safety profile needs to be demonstrated in order to potentially improve the risk/benefit in the eyes of the FDA who has been constraining enrollment criteria significantly. Leerink believes Thursday’s update could potentially help with value-creating pociredir news flow although timelines remain uncertain.

PRICE ACTION: In morning trading, shares of Pfizer is fractionally down at $28.85. Meanwhile, Fulcrum has jumped about 28% to $4.42. Also higher are Beam Therapeutics, Bluebird Bio, Editas Medicine, Crispr Therapeutics, and Emmaus Life Science.