Stem cell mobilising agent - plerixafor

Published: 12-Mar-2010
Regulatory Research & Development

Patients receiving a haematopoeietic stem cell transplant are also treated with an agent to...

Patients receiving a haematopoeietic stem cell - or bone marrow - transplant are also treated with an agent to mobilise the stem cells. This is typically granulocyte colony-stimulating factor (G-CSF) but there are large differences in response so new agents that have a more predictable effect would be extremely useful.

One such agent is Genzyme's plerixafor, acquired along with the company AnorMed.1 It acts at the CXCR-4 chemokine receptor, which has numerous signalling functions in the body, and also appears to be involved in stem cell mobilisation. The drug was originally designed as an anti-HIV agent, but was discontinued. However, it was also shown to increase peripheral leukocytes as it mobilised HSCs in the bone marrow by inhibiting the interaction between CXCR-4 and stromal cell-derived factor 1, and it is now being developed for this function.

In a Phase II study in autologous HSC transplantation in patients with relapsed or refractory Hodgkin lymphoma, 22 patients were given a combination of 10µg/kg G-CSF daily, plus 240µg/kg subcutaneous plerixafor 10-11 hours before apheresis.2 Results were compared with a historical control group who were given G-CSF alone. Two-thirds of the subjects met the primary endpoint of collecting at least 5x106 CD34+ cells/kg, and all bar one the minimum collection of 2 x106. This was a significant improvement over the historical control, and pharmacokinetics were similar to those seen in healthy volunteers.

Phase III trials have also been carried out. In one, 288 patients with non-Hodgkin's lymphoma undergoing autologous HSC transplantation were given 10µg/kg G-CSF for up to eight days, and then for four days from day four were also given 240µg/kg or placebo, with apheresis taking place daily from day five.3 The primary endpoint of 5x106 CD34+ cells/kg was met by 59% of those in the plerixafor group, and 20% of those given placebo.

As an add-on to this trial, patients on either arm who failed mobilisation were eligible for an open-label rescue protocol.4 These patients - 10 from the plerixafor arm and a further 52 from the placebo group - were given the same schedule again after a minimum seven-day rest period. Four of the pre-treated patients and 33 from the placebo group mobilised sufficient HSCs for transplantation. Common side-effects in the plerixafor group included mild gastro-intestinal effects and injection site reactions.

References

1. G. J. Bridger et al. J. Med. Chem. 1995, 38, 366

2. A. Cashen et al. Biol. Blood Marrow Transplant, 2008, 14, 1253

3. J. F. DiPersio et al. J. Clin. Oncol. 2009, 27, 4767

4. I. N. Micallef et al. Biol. Blood Marrow Transplant, 2009, 15, 1578

See more

You may also like

Manufacturing

UK pharmaceutical manufacturers struggling to meet F-Gas compliance amid ageing cooling infrastructure

Read more
A new Aggreko report reveals that nearly all UK pharmaceutical manufacturers are facing barriers to upgrading cooling systems ahead of the accelerating F-Gas phase-down timeline

Trending Articles

  1. FDA approves Lilly's oral GLP-1 pill Foundayo for obesity with no food or water restrictions Eli Lilly has received FDA approval for Foundayo (orforglipron), a once-daily oral GLP-1 receptor agonist for adults with obesity or overweight that requires no fasting or water restrictions, with clinical trial participants on the highest dose losing an average of 27 pounds
  2. FDA warns of drug-induced liver injury risk with Amgen's Tavneos after deaths The US Food and Drug Administration has issued a safety warning linking Amgen's vasculitis drug Tavneos to 76 cases of drug-induced liver injury globally, including eight deaths and seven cases of vanishing bile duct syndrome, recommending comprehensive liver monitoring during the first five months of treatment
  3. Pfizer's HYMPAVZI receives positive CHMP opinion for haemophilia A and B patients with inhibitors The EMA's Committee for Medicinal Products for Human Use has recommended expanding the approved indication for Pfizer's HYMPAVZI to include adolescents and adults with haemophilia A or B who have developed inhibitors to factor replacement therapies
  4. Evaporation and lyophilization for converting RP-HPLC peptide fractions into stable powders A method to obtain research peptides in a stable, dry, and contamination-free form for long-term storage
  5. From powder to granules: a deep dive into wet granulation methods - WEBINAR NOW ON DEMAND Join ACG in partnership with Manufacturing Chemist for an expert-led session to explore how different wet granulation methods impact consistency, yield, and quality — and what really matters when it comes to selecting and optimising your process

Upcoming event

Making Pharmaceuticals

21–22 April 2026 | Exhibition | Coventry, UK See all

You may also like

Manufacturing

UK pharmaceutical manufacturers struggling to meet F-Gas compliance amid ageing cooling infrastructure

A new Aggreko report reveals that nearly all UK pharmaceutical manufacturers are facing barriers to upgrading cooling systems ahead of the accelerating F-Gas phase-down timeline
Regulatory

UK REACH ATRm: CBA welcomes progress but warns of significant hurdles ahead

The Chemical Business Association has acknowledged long-awaited movement on the UK REACH Alternative Transitional Registration model following DEFRA's consultation response, but cautioned that cost burdens likely running into hundreds of millions of pounds
Regulatory

Lonza Nominates Stephen Fry as Independent Board Member

Basel, Switzerland, 31 March 2026 – The Lonza Board of Directors today announced the nomination of Stephen Fry as an Independent Member of the Board. Subject to his election at the Lonza Group Annual General Meeting (AGM) in May 2026, Stephen will also be appointed a member of the People and Governance Committee and the Audit and Compliance Committeex
Research & Development

Applied Biopharm Consulting awarded Innovation funding to validate AI-powered AAV vector engineering platform

Irish biotech consultancy Applied Biopharm Consulting has secured an Innovation Voucher from the Local Enterprise Office Cork North & West to collaborate with an academic partner in validating its computational platform for adeno-associated virus vector optimisation through laboratory testing
Manufacturing

L.B. Bohle hosts successful continuous manufacturing workshop in Brazil

Focus on continuous wet granulation and drying for research, development and small-scale production
Manufacturing

Swiss Rockets collaborates with Lonza to advance Torqur’s oncology drug candidate bimiralisib into late-stage clinical development

Lonza to provide cGMP manufacturing and technical support to advance bimiralisib into late-stage clinical development
Research & Development

Phesi analysis finds 6.7% of global clinical trials affected by Middle East disruption

A Phesi analysis of more than 65,000 active clinical trials has found that 4361 studies are impacted by Middle East disruption, with Phase III oncology trials most exposed and all top ten global pharma companies holding significant investigator site presence in affected countries
Subscribe now