Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 1108 |
| INN | Inclacumab |
| Status | Clinical |
| Drug code(s) | PF-07940370, RO4905417, RG1512 |
| Brand name | None |
| mAb sequence source | mAb human |
| General Molecular Category | Naked monospecific |
| Format, general category | Full length Ab |
| Format details | None |
| Isotype (Fc) | IgG4 |
| Light chain isotype | kappa |
| Linker | None |
| Ave. DAR | None |
| Conjugated/fused moiety | None |
| Discovery method/technology | Transgenic mouse (GenPharm/Medarex/BMS transgenic mouse platform) |
| Target(s) | P-selectin |
| Indications of clinical studies | Sickle Cell Disease, Peripheral Arterial Disease, Myocardial Infarction, Coronary Heart Disease, prevention of saphenous vein graft disease |
| Primary therapeutic area | Cardiovascular / hemostasis disorders |
| Most advanced stage of development (global) | Phase 3 |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | October 02, 2007 |
| Start of Phase 2 | December 15, 2010 |
| Start of Phase 3 | July 15, 2021 |
| Date BLA/NDA submitted to FDA | |
| Year of first approval (global) | None |
| Date of first US approval | |
| INN, US product name | None |
| US or EU approved indications | None |
| Company | Hoffmann-La Roche |
| Licensee/Partner | Pfizer |
| Comments about company or candidate | Phase 3 in Pfizer pipeline dated Oct 2024. NCT05348915 Phase 3 study active not recruiting as of Aug 2024. NCT04935879 Phase 3 study completed in June 2024. Mar 2024: NCT04927247 terminated terminated due to poor accrual and associated recrutiment challenges Phase 3 studies for Vaso-occlusive crisis in sickle cell disease patients (NCT05348915 is enrolling by invitation as of February 2023, NCT04927247 and NCT04935879 are recruiting as of February 2023). Aug 2022: Pfizer announced it was acquiring GBT; 2 Phase 3 studies have primary completion dates in 2023. Orphan Drug and Rare Pediatric Disease designations from the FDA. NCT04935879 Phase 3. In July 2021, the company initiated two global, randomized, placebo-controlled, pivotal Phase 3 trials evaluating the safety and efficacy of inclacumab, GBT’s P-selectin inhibitor, for the reduction of vaso-occlusive crisis (VOC) frequency and VOC-related hospital readmissions, respectively. NCT04927247 Phase 3 study in Sickle Cell Disease to start in July 2021. Pfizer acquired Global Blood Therapeutics Dec 2020: In 2021, GBT plans to initiate two global, randomized, placebo-controlled pivotal Phase 3 trials evaluating safety and efficacy of inclacumab. These trials are designed to enhance understanding of how P-selectin inhibitors could provide clinical benefit for patients with SCD and reduce overall healthcare utilization. One study is designed to reduce the frequency of VOCs over one year in patients with SCD when treated with inclacumab (30 mg/kg) or placebo every 12 weeks. The second study will evaluate inclacumab based on a primary endpoint of 90-day hospital readmission rates following a VOC hospitalization. Participants in that trial will receive either a single dose of inclacumab (30 mg/kg) or placebo, peri-discharge following a VOC hospitalization. Approximately 50 percent of U.S. SCD patients with least two annual VOC events are re-admitted within 90 days following a VOC hospitalization.1 Initiation of both trials is expected in the first half of 2021. Listed as preclinical with note "Manufacturing underway to enable IND for pivotal clinical trial expected in H1 2021" on company website accessed Aug 14, 2020: https://www.gbt.com/research/pipeline/. No further information about inclacumab found on GBT website as of Aug 2019, but it is listed as a GBT asset. August 2018: Global Blood Therapeutics acquired rights to Roche Holding's inclacumab, which Global Blood will develop to treat vaso-occlusive crises in patients with sickle cell disease. Under the terms of the agreement, Roche will get $2 million upfront plus up to $125 million in development and commercialization milestones and royalties on sales. Terminated by Roche for strategic reasons; Roche is seeking partnering options for inclacumab in ACS/CVD as of Jan 2014. Asset will be terminated if partner is not found because it is no longer a strategic fit; no safety or data concerns were found. |
| Full address of company | Basel, Switzerland Europe Switzerland https://www.roche.com/about |
Immune checkpoint target. Two single-point mutations were introduced into the Fc of inclacumab in order to avoid antibody-dependent cytotoxicity (L235E) and to improve structural stability (S228P). The L235E point mutation replaces a hydrophobic contact, reducing undesirable interactions by impairing Fc affinity for Fcγ receptors. Target is P-selectin (CD62)
| Anticipated events | BLA possible in 2024 |
| Factor(s) contributing to discontinuation | None |