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

Research & Development

From lab to launch: transforming pharmaceutical formulation development with GEA’s CFC Lab Coater

Read more
A new generation of continuous film coating technology is giving R&D teams the speed, precision and scalability they need to take products from the laboratory to commercial production without the traditional bottlenecks

Trending Articles

  1. FDA issues first cGMP warning letter citing AI misuse in pharmaceutical manufacturing A Michigan-based lab has become the subject of the FDA's first dedicated enforcement action on artificial intelligence misuse in drug manufacturing — a landmark event with far-reaching implications for cGMP compliance across the pharmaceutical supply chain
  2. Amarox recalls sertraline batch after citalopram blister strips found inside sealed cartons The MHRA has issued a class two recall of one batch of Amarox's sertraline 100 mg film-coated tablets following a secondary packaging error that resulted in citalopram 40 mg blister strips being included in sealed cartons
  3. Hongene to support SiranBio siRNA candidate programme with CDMO services The RNA specialist will support SiranBio's SA1211 programme, helping advance the siRNA candidate through its vertically integrated CDMO services to address the complex nature of the next-gen therapeutic
  4. MHRA report shows agency met targets and closed year in financial surplus The UK government agency has reported meeting or exceeding every statutory performance target in the 2025/26 financial year, closing in financial surplus while advancing clinical trials reform and AI regulation
  5. Scientists develop new technique to fight antimicrobial resistance The team of researchers from the University of Leicester have developed a new technique to sequence phage genomes from individual plaques and hopes to use it to build fully characterised libraries of bacteriophages, expanding the number of candidates available to tackle drug-resistant infections

Upcoming event

CHEMUK 2026

20–21 May 2026 | Conference and Exhibition | Birmingham, UK See all

You may also like

Research & Development

From lab to launch: transforming pharmaceutical formulation development with GEA’s CFC Lab Coater

A new generation of continuous film coating technology is giving R&D teams the speed, precision and scalability they need to take products from the laboratory to commercial production without the traditional bottlenecks
Manufacturing

Bristol Myers Squibb licenses Lonza ADC linker-payload technology for undisclosed target

BMS has secured exclusive access to Lonza’s SYNtecan linker-payload platform, alongside GlycoConnect and HydraSpace technologies, to advance development of an antibody-drug conjugate against an undisclosed target
Drug Delivery

Neuland Laboratories to partner with LIR Life Sciences for transdermal GLP-1 development

The pair will work to advance LIR Life's novel cell-penetrating peptides for next-generation obesity therapies, looking to improve patient adherence and broaden access
Hi Tech Manufacturing

Hongene to support SiranBio siRNA candidate programme with CDMO services

The RNA specialist will support SiranBio's SA1211 programme, helping advance the siRNA candidate through its vertically integrated CDMO services to address the complex nature of the next-gen therapeutic
Packaging

Amarox recalls sertraline batch after citalopram blister strips found inside sealed cartons

The MHRA has issued a class two recall of one batch of Amarox's sertraline 100 mg film-coated tablets following a secondary packaging error that resulted in citalopram 40 mg blister strips being included in sealed cartons
Research & Development

Reacta Healthcare announces expansion into Asia-Pacific and appoints Professor Gary Wing-Kin Wong to advisory board

Reacta Healthcare, a leading developer and manufacturer of pharmaceutical-grade oral food challenge (OFC) products for food allergy diagnostics, today announces the appointment of Professor Gary Wing-Kin Wong, internationally recognised paediatric allergy and respiratory disease expert and President-Elect of the World Allergy Organisation (WAO), to its Advisory Board, as the company accelerates new product development and expands its Asia-Pacific (APAC) footprint
Regulatory

MHRA report shows agency met targets and closed year in financial surplus

The UK government agency has reported meeting or exceeding every statutory performance target in the 2025/26 financial year, closing in financial surplus while advancing clinical trials reform and AI regulation
Subscribe now