The DNA damage repair drug olaparib (Lynparza), developed by AstraZeneca and Merck, has been approved by the EU as a first-line treatment preventing the return of ovarian cancer after initial chemotherapy.
The drug has already been approved by the EU and the FDA as a maintenance treatment for relapsed ovarian cancer, and as a therapy for breast cancer previously treated with chemotherapy. This latest approval expands the use of the drug to a first-line maintenance therapy to prevent ovarian cancer from relapsing after chemotherapy.
Lynparza inhibits a protein called PARP, which is required for the repair of DNA molecules. The drug is able to attack tumors by stopping cancer cells from replicating properly. PARP inhibitor drugs such as Lynparza are especially effective in tumors with mutations to other proteins involved in DNA repair, such as BRCA1 and BRCA2.
The approval was based on positive results from a phase III trial in ovarian cancer patients. The patients’ tumors had been shrunk by chemotherapy prior to the trial and contained mutated forms of the BRCA1 and BRCA2 proteins. Used as a maintenance therapy over three years, Lynparza reduced the risk of disease progression or death by 70% compared with placebo.
“The goals of front-line therapy have always been long-term remission and even cure, yet currently 70% of patients relapse within three years of initial treatment,” stated Dave Fredrickson, Executive Vice President of the Oncology Business Unit at AstraZeneca.
Lynaparza is well on its way to becoming a blockbuster treatment. Keen to maximize the potential of the drug, AstraZeneca and Merck are busy testing Lynparza in other indications. One phase III trial is testing the drug as a first-line therapy for ovarian cancer in combination with the antibody drug bevacizumab.
The CEO of UK biotech Artios Pharma, Niall Martin, was involved in the initial development of Lynparza in his days at the UK biotech KuDOS Pharma, which was acquired by AstraZeneca in 2005. “It has taken a long time for this [program] to come to fruition but it is great to see that many of the cancers we predicted it would work in are now showing results,” he told me.
According to Martin, the latest approval shows that PARP inhibitors have the potential to treat many different types of tumors, as long as they have a genetic predisposition to the drug. “The way that we will be looking at cancer soon is not by tumor type, such as breast and ovarian, but by mutational signature or genetic loss, such as BRCA,” he said.
Although DNA damage repair inhibitor drugs in cancer have been slow to reach the attention of pharma companies over the last 10 years, the field is taking off now. “Many large pharma companies have focussed mainly on the immune oncology space and DNA damage repair has been ignored largely, until now,” Martin commented.
PARP inhibitors aren’t the only approach to disrupting DNA damage repair in cancer. Martin’s company Artios Pharma is developing drugs targeting a different DNA damage repair protein. The French biotech Onxeo is developing DNA drugs preventing the DNA repair proteins from working in cancer cells. These drugs are designed to prevent the tumor from becoming resistant to the treatment, which is a risk in PARP inhibitor drugs.
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