MedPath

Crizanlizumab

Generic Name
Crizanlizumab
Brand Names
Adakveo
Drug Type
Biotech
CAS Number
1690318-25-2
Unique Ingredient Identifier
L7451S9126
Background

Crizanlizumab is a humanized IgG2 monoclonal antibody used to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease. Sickle cell disease is a genetically inherited condition prevalent in the Middle East, Africa, and certain parts of India. The genetic mutation associated with this disease leads to the formation of abnormal, sickle shaped red blood cells that aggregate and block blood vessels throughout the body, causing vaso-occlusive crises. Sickle cell disease can lead to excruciating pain, stroke, infection, and various other complications arising from the blockage of blood vessels.

Currently, patients are prescribed hydroxyurea to raise levels of fetal hemoglobin as a method of reducing morbidity and mortality. Though hydroxyurea has been shown to reduce the frequency of vaso-occlusive crises, adherence to this therapy is difficult due to adverse effects and the high variability of response to the drug between patients. Crizanlizumab, or SEG101, is given once every 4 weeks and may improve patient adherence. It was developed by Novartis and was granted FDA approval on November 15, 2019. While crizanlizumab received conditional marketing authorization from the EMA in October 2020, this approval was revoked in August 2023 due to concerns over the efficacy and safety of the drug.

Indication

Crizanlizumab is indicated to reduce the frequency of vaso-occlusive crisis in patients with sickle cell diseases who are ≥16 years old.

Associated Conditions
Vaso-occlusive Crisis

Pfizer Withdraws Sickle Cell Drug Oxbryta Globally Following Safety Concerns

• Pfizer has voluntarily withdrawn its sickle cell disease therapy Oxbryta (voxelotor) from all global markets after discovering an imbalance in deaths during clinical trials. • The withdrawal marks a significant setback for the sickle cell community as Oxbryta was the first approved medication that directly prevented sickle hemoglobin polymerization, the molecular basis of the disease. • The decision follows Pfizer's $5.4 billion acquisition of Global Blood Therapeutics in 2022, with Oxbryta having generated $328 million in sales last year and previously projected to reach $2 billion in peak annual revenue.

CRISPR Therapeutics Faces Slow Casgevy Launch Despite Regulatory Approvals

• CRISPR Therapeutics' stock has declined despite the FDA and EU approvals of Casgevy for sickle cell disease and transfusion-dependent beta thalassemia. • The initial launch of Casgevy, developed with Vertex Pharmaceuticals, has been slower than anticipated due to the complexity of the treatment and conditioning regimen. • CRISPR Therapeutics is advancing five other clinical-stage therapy candidates, including CTX112 for blood cancers, with promising early trial results. • Despite current losses, CRISPR Therapeutics maintains a strong cash position, providing a runway for Casgevy sales growth and pipeline development.

CRISPR Therapeutics Faces Slow Casgevy Launch Despite Regulatory Approvals

• CRISPR Therapeutics' stock has declined despite FDA and EU approvals of Casgevy for sickle cell disease and transfusion-dependent beta thalassemia. • Casgevy's initial sales have been slow due to the complexity of the therapy and a conditioning regimen that carries risks. • Promising Phase 1 trial results for CTX112, a blood-cancer treatment, and a strong cash position offer potential for future growth. • Analysts suggest caution due to the high-risk nature of the stock, advising investors to consider their risk tolerance.

CRISPR Therapeutics Faces Market Challenges Despite Casgevy Approval

• CRISPR Therapeutics' stock has declined 47% since March, despite FDA and EU approval of Casgevy for sickle cell disease and transfusion-dependent beta thalassemia. • Casgevy's initial launch has been slower than expected due to complex administration and the need for a conditioning regimen, impacting revenue. • ARK Investment Management shows bullish sentiment by increasing its stake in CRISPR Therapeutics, viewing gene editing as a valuable long-term investment. • CRISPR Therapeutics is advancing CTX112, an experimental blood-cancer treatment, with promising Phase 1 results showing tumor shrinkage in lymphoma patients.

Patient Death in Beam Therapeutics' Sickle Cell Trial Linked to Conditioning Regimen

• A patient in Beam Therapeutics' BEACON trial of BEAM-101, a base editing therapy for sickle cell disease (SCD), died four months post-infusion due to respiratory failure. • Investigators determined the death was likely related to the busulfan conditioning regimen and not directly caused by BEAM-101, according to Beam Therapeutics. • The FDA and the BEACON trial's Data Safety Monitoring Committee reviewed the death, allowing the trial to proceed without protocol changes. • The event underscores the need for less toxic preconditioning options in cell and gene therapy, as current regimens are associated with significant toxic effects.

Pfizer Withdraws Sickle Cell Disease Drug Oxbryta Globally Due to Safety Concerns

• Pfizer has voluntarily withdrawn Oxbryta (voxelotor) from all global markets due to safety concerns, citing an imbalance in vaso-occlusive crises and fatal events. • The decision follows a review of clinical data that indicated the overall benefit of Oxbryta no longer outweighs the risks for sickle cell disease patients. • Regulatory agencies, including the EMA and FDA, have alerted healthcare professionals and patients about the withdrawal, advising discussions on alternative treatments. • The withdrawal impacts ongoing clinical trials and expanded access programs, leaving the sickle cell community seeking alternative treatment options and raising concerns about trust.

Novartis Highlights New Data on Kisqali, Iptacopan, and Scemblix at SABCS and ASH

• Final analysis of the NATALEE trial showed Kisqali (ribociclib) significantly improved invasive disease-free survival in HR+/HER2- early breast cancer patients. • APPLY-PNH trial data demonstrated iptacopan monotherapy's sustained efficacy and safety in anti-C5-treated PNH patients with persistent anemia over 48 weeks. • Scemblix (asciminib) showed sustained efficacy and safety after nearly 4 years in CML-CP patients who failed ≥2 prior tyrosine kinase inhibitors.
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