CLINICAL TRIALS PROFILE FOR MOZOBIL

All Clinical Trials for Mozobil

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00075335 ↗	AMD 3100 (Mozobil Plerixafor) to Mobilize Stem Cells for Donation	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 2	2004-01-01	Peripheral blood progenitor cells (PBPC) have become the preferred source of hematopoetic stem cells for allogeneic transplantation because of technical ease of collection and shorter time required for engraftment. Traditionally, granulocyte-colony stimulating factor (G-CSF) has been used to procure the peripheral blood stem cell graft. Although regimens using G-CSF usually succeed in collecting adequate numbers of PBPC from healthy donors, 5%-10% will mobilize stem cells poorly and may require multiple large volume apheresis or bone marrow harvesting. Although G-CSF is generally well tolerated in healthy donors, it may be associated with bone pain, headache, myalgia and rarely life threatening side effects like stroke, myocardial infarction and splenic rupture. AMD3100, is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 (SDF-1) to its cognate receptor CXC- chemokine receptor 4 (CXCR4). CXCR4 is present on cluster of differentiation 34 (CD34)+ hematopoetic progenitor cells and its interaction with stromal cell derived factor 1 (SDF-1) plays a pivotal role in the homing of CD34+ cells in the bone marrow. Inhibition of the CXCR4-SDF1 axis by AMD3100 releases CD34+ cells into the circulation, which can then be collected easily by apheresis. Recently, a published report demonstrated that large numbers of CD34+ cells were rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100. Remarkably, the number of CD34+ cells collected by apheresis following a single injection of AMD3100 was comparable to the number of CD34+ cells collected from historical controls receiving 5 days of G-CSF prior to stem cell mobilization. In this study we will collect PBPCs following a single subcutaneous injection of AMD3100 from healthy donors who have previously had PBPC collected using standard G-CSF mobilization. The AMD3100 mobilized cells, G-CSF mobilized cells, and circulating cells prior to both AMD3100 and G-CSF mobilization will be analyzed in terms of cellular content and function of lymphocytes, natural killer (NK) cells, and antigen presenting cells. AMD3100 mobilized PBPC will be collected for the purpose of research studies and will not be used for therapeutic purposes.
NCT00082329 ↗	G-CSF and AMD3100 to Mobilize Stem Cells in Healthy Volunteers	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 2	2004-06-18	This 12-day study will test whether the combination of G-CSF (granulocyte-colony stimulating factor) and AMD3100 (Mozobil) is more efficient in mobilizing stem cells for collection than the use of G-CSF alone. Traditionally, the growth factor G-CSF has been given to stem cell donors to mobilize, or push, stem cells out of the bone marrow and into the blood circulation for collection for transplantation. Although a sufficient quantity of cells usually can be collected with G-CSF treatment, some donors do not respond well and may require multiple apheresis procedures (see below) to collect enough cells. Studies indicate that G-CSF used together with a drug called AMD3100 may be more effective in mobilizing stem cells for collection than G-CSF alone. The Food and Drug Administration has approved G-CSF for stem cell mobilization. AMD3100 is a new drug that also mobilizes stem cells in large numbers within a few hours. Normal healthy volunteers between 18 and 60 years of age may be eligible for this study.
NCT00082329 ↗	G-CSF and AMD3100 to Mobilize Stem Cells in Healthy Volunteers	Completed	Richard Childs, M.D.	Phase 2	2004-06-18	This 12-day study will test whether the combination of G-CSF (granulocyte-colony stimulating factor) and AMD3100 (Mozobil) is more efficient in mobilizing stem cells for collection than the use of G-CSF alone. Traditionally, the growth factor G-CSF has been given to stem cell donors to mobilize, or push, stem cells out of the bone marrow and into the blood circulation for collection for transplantation. Although a sufficient quantity of cells usually can be collected with G-CSF treatment, some donors do not respond well and may require multiple apheresis procedures (see below) to collect enough cells. Studies indicate that G-CSF used together with a drug called AMD3100 may be more effective in mobilizing stem cells for collection than G-CSF alone. The Food and Drug Administration has approved G-CSF for stem cell mobilization. AMD3100 is a new drug that also mobilizes stem cells in large numbers within a few hours. Normal healthy volunteers between 18 and 60 years of age may be eligible for this study.
NCT00103610 ↗	Mobilization of Stem Cells With AMD3100 (Plerixafor) in Non-Hodgkin's Lymphoma Patients	Completed	Genzyme, a Sanofi Company	Phase 3	2005-01-01	The purpose of this study is to determine whether the combination of AMD3100 (plerixafor) and granulocyte colony-stimulating factor (G-CSF or generic name filgrastim) is better than G-CSF alone to mobilize and collect the optimal number of stem cells in non-Hodgkin's lymphoma patients for autologous transplantation.
NCT00103662 ↗	Mobilization of Stem Cells With AMD3100 (Plerixafor) in Multiple Myeloma Patients	Completed	Genzyme, a Sanofi Company	Phase 3	2005-01-01	The purpose of this study is to determine whether the combination of AMD3100 (plerixafor) and granulocyte colony-stimulating factor (G-CSF, generic name of filgrastim) is better than G-CSF alone to mobilize and collect the optimal number of stem cells in multiple myeloma patients for autologous transplantation.
NCT00322387 ↗	Mobilization of Stem Cells With Plerixafor, Chemotherapy and G-CSF in Multiple Myeloma or Non-Hodgkin's Lymphoma Patients	Completed	Genzyme, a Sanofi Company	Phase 2	2004-04-01	Patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL) will be mobilized with chemotherapy and G-CSF plus plerixafor (AMD3100). The purpose of this protocol is to determine if plerixafor given after chemotherapy and G-CSF mobilization regimen is safe, if it can increase the circulating levels of peripheral blood stem cells (PBSCs) by ≥ 2-fold before apheresis, and if transplantation with the apheresis product was successful, as measured by time to engraftment of polymorphonuclear leukocytes (PMNs) and platelets (PLTs).
NCT00322491 ↗	Mobilization of Stem Cells With AMD3100 (Plerixafor) and G-CSF in Non-Hodgkin's Lymphoma and Multiple Myeloma Patients	Completed	AnorMED	Phase 2	2004-03-01	This study evaluates the safety and efficacy of plerixafor given in addition to granulocyte-colony stimulating factor (G-CSF) for collection of peripheral blood stem cells (PBSCs) for autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Efficacy outcomes include evaluation of fold increase in circulating CD34+ cells from just before the first plerixafor injection to 10-11 hours post plerixafor (just before apheresis) and assessment of successful polymorphonuclear leukocyte (PMN) engraftment after transplantation. Data from this protocol will assist in the determination of the dosing schedule for future studies.

Clinical Trial Conditions for Mozobil

Condition Name

Condition Name for Mozobil
Intervention	Trials
Multiple Myeloma	17
Acute Myeloid Leukemia	5
Lymphoma	5
Lymphoma, Non-Hodgkin	5

Condition MeSH

Condition MeSH for Mozobil
Intervention	Trials
Multiple Myeloma	21
Neoplasms, Plasma Cell	20
Lymphoma, Non-Hodgkin	19
Lymphoma	19

Clinical Trial Locations for Mozobil

Trials by Country

Trials by Country for Mozobil
Location	Trials
United States	150
Canada	10
Italy	5
Germany	3
France	2

Trials by US State

Trials by US State for Mozobil
Location	Trials
California	17
Missouri	12
New York	11
Washington	11
Massachusetts	8

Clinical Trial Progress for Mozobil

Clinical Trial Phase

Clinical Trial Phase for Mozobil
Clinical Trial Phase	Trials
Phase 4	2
Phase 3	4
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for Mozobil
Clinical Trial Phase	Trials
Completed	53
Terminated	13
Recruiting	9

Clinical Trial Sponsors for Mozobil

Sponsor Name

Sponsor Name for Mozobil
Sponsor	Trials
Genzyme, a Sanofi Company	30
National Cancer Institute (NCI)	13
Washington University School of Medicine	6

Sponsor Type

Sponsor Type for Mozobil
Sponsor	Trials
Other	94
Industry	45
NIH	25

Mozobil: Clinical Trials, Market Analysis, and Projections

Introduction to Mozobil

Mozobil, also known by its active substance plerixafor, is a medication used to mobilize hematopoietic stem cells from the bone marrow into the peripheral blood for collection and subsequent autologous transplantation. It is primarily indicated for patients with non-Hodgkin’s lymphoma and multiple myeloma who have poor mobilization of stem cells[1][4].

Clinical Trials and Efficacy

Adult Studies

In two major studies involving 298 adults with non-Hodgkin’s lymphoma and 302 adults with multiple myeloma, Mozobil demonstrated significant efficacy. When used in combination with granulocyte-colony-stimulating factor (G-CSF), Mozobil showed that more patients achieved the target number of stem cells and had successful engraftment compared to those receiving placebo. For non-Hodgkin’s lymphoma patients, 59% of those receiving Mozobil achieved the target number of stem cells within 4 collection days, compared to 20% of those receiving placebo. For multiple myeloma patients, 72% achieved the target number of stem cells, compared to 34% of the placebo group[1].

Pediatric Studies

In a study involving 45 children with lymphoma or solid tumors, Mozobil was found to significantly increase the number of stem cells in the blood. 80% of patients who received Mozobil had at least a doubling of the number of stem cells, compared to 29% of patients who received standard mobilization treatment alone[1].

Mechanism of Action

Mozobil works by blocking the activity of the CXCR4 chemokine receptor, a protein that normally keeps stem cells within the bone marrow. By inhibiting this receptor, Mozobil allows the stem cells to be released into the peripheral blood, where they can be collected for transplantation[1].

Side Effects and Safety

Common side effects of Mozobil include diarrhea, nausea, and reactions at the site of injection. These side effects are generally manageable and do not often lead to discontinuation of the treatment[1].

Market Analysis

Current Market Performance

Mozobil has faced significant challenges in recent times due to the entry of generic competition. In the fourth quarter of 2023, Mozobil sales were down 50.7% to €33 million, reflecting the impact of generic competition in the U.S. which began in July 2023[2].

Market Size and Growth

The U.S. market for mobilization agents used in stem cell transplants is estimated to be approximately $360 million annually and is growing. However, the entry of generics and other competitors, such as Motixafortide (APHEXDA), which is under review by the FDA, may further impact Mozobil's market share[3].

Competitive Landscape

Generic Competition

The introduction of generic versions of Mozobil has significantly impacted its sales. Generic competition, which started in the U.S. in July 2023, has led to a substantial decline in Mozobil's revenue[2].

Emerging Competitors

BioLineRx's Motixafortide (APHEXDA) is a new therapeutic candidate that has shown promising results in clinical trials for stem cell mobilization. The GENESIS Phase 3 trial demonstrated that Motixafortide, when used in combination with G-CSF, was superior to G-CSF alone in mobilizing hematopoietic stem cells. This could pose a significant challenge to Mozobil's market position if approved by the FDA[3].

Projections and Future Outlook

Sales Projections

Given the current market dynamics, Mozobil's sales are expected to continue declining due to generic competition and the potential approval of new competitors like Motixafortide. Sanofi's financial reports indicate that the impact of generic competition on Mozobil will be a significant factor in the coming quarters[2].

Market Share

Mozobil's market share is likely to decrease as generic versions and new competitors gain traction. The U.S. market, in particular, will see increased competition, which could lead to a further erosion of Mozobil's market position[2][3].

Key Takeaways

• Efficacy: Mozobil has been shown to be effective in mobilizing hematopoietic stem cells for autologous transplantation in patients with non-Hodgkin’s lymphoma and multiple myeloma.
• Market Challenges: The drug faces significant challenges due to generic competition and emerging competitors.
• Future Outlook: Sales are projected to decline as generic and new competitor presence increases in the market.
• Mechanism of Action: Mozobil works by blocking the CXCR4 chemokine receptor, allowing stem cells to be released from the bone marrow into the peripheral blood.

Frequently Asked Questions

What is Mozobil used for?

Mozobil is used to mobilize hematopoietic stem cells from the bone marrow into the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma and multiple myeloma[1][4].

How does Mozobil work?

Mozobil works by blocking the activity of the CXCR4 chemokine receptor, which normally keeps stem cells within the bone marrow, allowing them to be released into the peripheral blood[1].

What are the common side effects of Mozobil?

Common side effects include diarrhea, nausea, and reactions at the site of injection[1].

Why have Mozobil sales declined recently?

Mozobil sales have declined due to the entry of generic competition in the U.S. market, which started in July 2023[2].

What are the potential competitors to Mozobil?

Emerging competitors include Motixafortide (APHEXDA), which has shown promising results in clinical trials and is under review by the FDA[3].

Cited Sources

1. European Medicines Agency (EMA). Mozobil | European Medicines Agency (EMA).
2. Sanofi. Press Release Q4 2023 English - Sanofi.
3. BioLineRx. BioLineRx Announces U.S. Commercialization Plan for APHEXDA (Motixafortide) in Stem Cell Mobilization.
4. Aetna. Plerixafor - Medical Clinical Policy Bulletins - Aetna.