La Merie

Smaller is better for thrombopoiesis-stimulating agents

BARCELONA, Spain | October 10, 2005 | The Business Intelligence firm La Merie S.L. recently analyzed the pipeline of thrombopoietin-stimulating agents. Main outcome of the search was that only two recombinant macromolecular proteins of the many projects initiated in the last decade are left. These protein projects are closely followed by oral small molecule and recombinant small protein developments which offer more convenience in dosing and less risk for immunogenicity. The latter one has been a major reason for discontinuation of first generation protein projects. The two macromolecular proteins are a recombinant human thrombopoietin having completed clinical development in China and Amgen’s “peptibody” protein AMG 531 in mid-stage clinical devleopment for treatment of thrombocytopenia. At least six small molecule and small protein projects are in various stages of R&D but clinical superiority still has to be proven. The results of this analysis were published in the October 10 issue of R&D Pipeline News, edited by La Merie.

While chemotherapy-induced anemia and leukopenia can be treated with the corresponding recombinant human growth factor erythropoietin and granulocye-colony stimulating factor (G-CSF), platelet transfusion still is the only treatment modality for thrombocytopenia. Clinical use of recombinant versions of human thrombopoietin (rhu-TPO) of the first generation (discovered only in 1994) was hampered by 1) induction of antibodies crossreacting with native TPO; 2) its failure in myeloablative chemotherapy regimens; and 3) the need for prolonged administration over 2-3 weeks (because of its action on precursor cells and not mature cells) resulting in a small window of opportunity. Apparently, the pharmaceutical industry lost interest and many companies abandoned projects with macromolecular TPO-stimulating agents (Pharmacia/Pfizer; 3D Pharmaceuticals/J&J; Schering-Plough; Alexion/XOMA), partly also due to technical difficulties with agonistic antibodies.

This prompted the search for small molecules with TPO-like activity. GlaxoSmithKline was successful in bringing two different oral small molecules into clinical evaluation of treatment of thrombocytopenia due to hepatitis C, refractory idiopathic thromboytopenic purpura and chemotherapy. Other new chemical entities or derivatives of marine fungi were discovered by Japanese companies, but still are in preclinical R&D. The japanese company Chugai is leading the field of recombinant small proteins acting via dimerization of the TPO-receptor. This “minibody” is the dimeric covalent antibody fragment VB22B. A similar approach was undertaken by a German company leading to a recombinant “microbody” which showed proof of concept in mice.

About La Merie
La Merie S.L. is a Business Intelligence enterprise fully dedicated to provide high quality R&D information to the biopharmaceutical industry. La Merie offers individual consultancy services and publishes reports and periodicals. For more information visit www.lamerie.com .

About R&D Pipeline News
R&D Pipeline News is a premier information source about research and development projects in the pipeline of the biopharmaceutical industry and is directed to all stakeholders in R&D. The weekly publication comes in a rapid- and easy-to-screen tabular format and provides access to the original information source via hyperlinks. R&D Pipeline News covers all relevant treatment modalities and is directly delivered to the desktop via e-mail. More information about the journal, a free trial and subscriptions are available via the website, www.lamerie.com.

SOURCE: La Merie Business Intelligence

[ top of the page ]