A drug for ovarian cancer that was written off by AstraZeneca (AZ) at the end of 2011 has now progressed to pivotal studies after a change of heart at the pharma giant.
Enrolment is underway in a phase III programme looking at olaparib as a treatment for ovarian cancer patients with BRCA gene mutations. Called SOLO, the trials will assess the drug as maintenance monotherapy in women who have responded to platinum-based chemotherapy.
The programme consists of two studies; SOLO 1 will examine first-line treatment with olaparib while SOLO 2 will involve patients who have relapsed after chemotherapy.
A spokesperson for AZ told PMLiVE that the initial decision to halt development of olaparib was taken on the back of a re-analysis of a phase II trial reported in 2011 which showed that the drug improved progression-free survival (PFS) in ovarian cancer patients by around three months.
That level of efficacy - along with the fact that the capsule formulation of olaparib used in the trial meant that patients had to take eight capsules a day - prompted the company to place the drug's development "on hold", she said.
The company continued to sift through the data, however, and decided to look at the effect of olaparib specifically on patients in the trial with the BRCA mutation, who accounted for around half of the total study population.
That analysis revealed a PFS of more than eight months, well above the threshold to take the project forward, and was presented earlier this year at the American Society of Clinical Oncology (ASCO) conference. Meanwhile, AZ has also successfully developed a new formulation of olaparib that can be given as four tablets per day, said the spokesperson.
Patients will be selected for treatment in the SOLO studies using a BRCA companion diagnostic developed by Myriad Genetics.
In addition to resurrecting the phase III programme in ovarian cancer for olaparib, AZ is also preparing for additional studies in cancers linked to BRCA mutations, including breast cancer, and will look at the drug in combination with other therapies in prostate and gastric cancers.
AZ booked a $285m charge as a result of its decision to drop olaparib, and now says this will be reversed in its third-quarter results statement.
Olaparib is a poly ADP ribose polymerase (PARP) inhibitor, a drug class which is starting to live up to its early promise as a means of treating cancer by blocking the repair of DNA in tumour cells despite some early clinical setbacks.
The recent demise of Sanofi's rival candidate iniparib after a phase III trial failure means that AZ is among the leaders in the PARP inhibitor field, although several other drugs are coming through the clinical pipeline.
Tesaro recently started a phase III programme for its niraparib (formerly developed by Merck & Co) in ovarian cancer, while other PARP inhibitors in trials include BioMarin's BMN-673 and Clovis Oncology's rucaparib (which was originated by Pfizer).