sanofi-aventis and PARP inhibitors
Three years ago I wrote about PARP inhibitors and how they were an 'early but promising approach' yet sadly nothing much seems to have changed since then. It was therefore a big surprise to read in the news today that sanofi-aventis are purchasing BiPar Science for $500M. This little biotech has two PARP inhibitors and an anti-tubulin in development (one in phase II and the others still in preclinical), making the pipeline acquisition a long shot at best. Positive data was presented on the lead candidate BSI-201 at the San Antonio Breast Cancer Symposium last December in triple negative breast cancer, which usually confers poor prognosis for those women who are ER-, PR-, and HER2- negative. Another trial is recruiting patients with newly diagnosed malignant glioblastoma.
What else has happened to PARP inhibitors in the intervening years since the last blog post? Well, the one mentioned then, Inotek's INO-101 (for malignant melanoma) appears not to be developed by Genentech anymore looking at the two companies pipelines, although Inotek are still researching the area with new agents being developed for retinal diseases such as AMD and diabetic retinopathy.
Around the pharma R&D world, there appears to be a few PARP inhibitors in varying stages of development, although not all for the same indications. MGIPharma (now Eisai), for example, are looking at the class for their potential to act as chemo and radiosensitisers. Pfizer's AG014699 has been tested in phase I advanced malignant melanoma in combination with temozolomide and appears to be well tolerated.
AstraZeneca and KuDOS are partnering to develop KU-0059436 (AZD2281) in advanced solid tumors, a trial that is currently recruiting patients to be treated with standard carboplatin-Taxol with and without the PARP inhibitor. Another trial is also recruiting pancreatic cancer patients to be treated with gemcitabine, with and without KU-0059436. Other trials involve breast and ovarian cancer with the agent.
Merck are testing MK4827 in advanced solid tumours and BRCA mutant breast cancer while Abbott are looking at ABT-888 in combination with temozolomide in a variety of different advanced solid tumours.
There are probably a few other agents, so if I've missed any, please do add them in the comments section under this blog. Hopefully, I'll find out more this weekend at the AACR annual meeting in Denver, CO.
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2 Responses to “sanofi-aventis and PARP inhibitors”
I can’t help but think PARP’s are one of those drug classes that never quite delivers. But I am always hoping somebody will work out how to make them work, I suspect the answer lies in clever combintion/patient selection. No doubt an academic/medic will stumble across the answer before the “drug development professionals” if not in a totaly obscure indication. Thanks for another interesteing overview. Bring on the academics with their huge brains.
Damien
I know what you mean, Damien. That was kind of what I was thinking after realising things haven’t changed much in 3 years.
We should remember the VEGF and Avastin story though – many failures and finally that one came through and bingo, you have a blockbuster.
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