Results of GSK and AstraZeneca trials may widen ovarian cancer drug use

BARCELONA (Reuters) – GlaxoSmithKline and AstraZeneca both reported trial results that will likely make their competing drugs available to a wider group of ovarian cancer patients, possibly helping GSK catch its rival in a highly contested drug class.

The two said separately on Saturday their drug candidates – in a class known as PARP inhibitors – staved off the return of metastasized ovarian cancer in women who had responded to initial standard treatment, reducing the risk of a relapse.

AstraZeneca and its U.S. development partner Merck & Co said their Lynparza drug cut the risk of the cancer progressing again by 41%. The figure was 38% for GSK’s drug.

The companies said they would discuss the results with healthcare regulators with a view to a wider label.

Analysts have seen AstraZeneca and Merck’s Lynparza in the lead with an average sales estimate of $3.1 billion for 2023. GSK’s Zejula is seen achieving about 870 million pounds ($1.1 billion) in revenue that year.

But different trial settings will make it difficult to predict how physicians will weigh up the two drugs.

While the Lynparza trial worked on the assumption that patients get an initial treatment of chemotherapy plus Roche’s Avastin, the trial with GSK’s Zejula included only patients who had initially gone through chemotherapy only.

AstraZeneca argues that more than half of advanced ovarian cancer patients in developed countries already get Avastin, with the rate increasing, while GSK says concerns about side effects may speak against the Roche drug.

Both companies, which are competing to burnish their oncology credentials, showed that not just the small group of women with mutated BRCA genes can benefit as the results also covered the full variety of ovarian cancer.

Many cancer cells have a limited ability to make DNA repairs during cell division, as healthy cells would. This feature makes tumors genetically volatile and helps them develop resistance to treatment over time.

GENETIC MUTATIONS

Drugmakers try to use that to their advantage with PARP inhibitors, which block what is left of the DNA repair mechanism so cancer cells fail to replicate. Mutated BRCA genes make the DNA repair particularly weak, which is why PARP inhibitors have been approved already for that subgroup.

Both trials showed benefit in using Zejula or Lynparza also in tumors with a wider range of genetic mutations that hamper DNA repairs, grouped together under the term homologous recombination deficiency (HRD).

But in a patient subgroup with tumors where the DNA repair was still intact, GSK appears to make headway over its rivals.

That group, which according to GSK accounts for about half of ovarian cancer cases, showed a reduction in the cancer relapse risk by 32%, when given Zejula.

In the Lynparza trial, however, there was no meaningful benefit in that cohort. But reliable tests on HRD have yet to become widely available.

“We know now we can use PARP inhibitors in the first-line setting beyond women with BRCA mutations,” said Susana Banerjee, an oncologist at the Royal Marsden NHS Foundation Trust in London, who discussed the results at an ESMO press conference.

“I think the key question really is, what about patients that don’t have HR deficiency?” Banerjee added.

Zejula was the lead compound of U.S. cancer specialist Tesaro, which GSK acquired for $5.1 billion in December.

Other approved PARP inhibitors, Pfizer’s Talzenna and Clovis Oncology’s Rubraca, are seen as further behind in terms of future revenue prospects. Abbvie is testing an experimental compound called veliparib.