Positive CHMP opinion for rucaparib in advanced ovarian cancer

20th October 2023

Rucaparib has been given a positive opinion as a first-line maintenance treatment for patients with advanced ovarian cancer by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP), its manufacturer Pharma& has announced.

Suitable for all women with advanced ovarian cancer, regardless of BRCA mutation status, who have responded to first-line platinum-based chemotherapy, rucaparib (brand name Rubraca) is a poly-ADP ribose polymerase (PARP) inhibitor.

The targeted cancer drug is currently approved as a monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who have a complete or partial response to platinum-based chemotherapy.

The recent recommended approval from the CHMP is a Type II variation on the current license and is based on the randomised, double-blind, placebo-controlled, phase 3 ATHENA-MONO trial results.

The trial demonstrated that rucaparib significantly improved investigator-assessed progression-free survival compared with placebo in women, regardless of their BRCA mutation status in each of the populations studied.

The safety profile observed in the ATHENA-MONO trial was consistent with both the current US and European labels for rucaparib.

Dr Rebecca Kristeleit, consultant medical oncologist and adjunct reader at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London, and European Network of Gynaecological Oncological Trial (ENGOT) lead of the ATHENA trial, said: ‘In the ATHENA-MONO trial, rucaparib prolonged progression-free survival, irrespective of molecular characteristics, and its potential approval by the European Medicines Agency as a first-line maintenance treatment is an important step forward in this difficult-to-treat population.

‘Women with advanced ovarian cancer need and deserve new treatment options to improve outcomes, and [this] recommendation is hopeful news for eligible patients in Europe.’

The European Commission will now review the positive opinion and Pharma& anticipates an approval decision in the coming months.

Elmar Zagler, founder and managing director, Pharma&, said: ‘Accessing effective medicines is the primary goal for both healthcare providers and patients, and it can be devastating when these medicines are no longer available.

‘Over the last five years, Pharma& has established itself as an agile, fully integrated global company that aspires to breathe new life into proven medicines like rucaparib.’

Earlier this year, rucaparib was found to improve progression-free survival in metastatic, castration-resistant prostate cancer with BRAC alteration compared to usual care.

Novel MOv18 IgE antibody shows potential as ovarian cancer therapy

27th July 2023

The chimeric first-in-class immunoglobulin E (IgE) antibody MOv18 appears to have a manageable safety profile for cancer therapy, with additional evidence of anti-tumour activity in a patient with ovarian cancer.

Published in the journal Nature Communications, the researchers conducted a Phase I dose escalation trial, with the primary objective of exploring the safety and tolerability of the MOv18 IgE antibody.

The MOv18 antibody targets the human folate receptor-alpha (FRα) that is over-expressed in tumours such as ovarian, breast and lung cancers, but remains at low levels in normal tissue.

Eligible patients were over 16 years of age and had advanced or metastatic solid tumours that were not suitable for alternative standard treatment. In addition, all were required to have a solid tumour expressing FRα, although the majority had advanced ovarian cancer which had become platinum-resistant.

MOv18 IgE safety

A total of 26 patients were enrolled and, overall, MOv18 IgE was generally well tolerated with the majority of adverse events being low grade. The most common events were localised cutaneous toxicities including urticaria, pruritus and rash, which appeared to be dose-related. Furthermore, the urticaria always resolved within hours of dosing, either spontaneously or with the administration of systemic steroids and antihistamines.

Although the primary focus of the study was the safety of MOv18 rather than efficacy, tumour shrinkage and an associated fall in the CA125 tumour marker level, was seen in one patient. Notably, the study authors observed that the anti-tumour activity ‘occurred at doses very much lower than typically observed for IgG antibodies‘, reflecting fundamental differences in Fc-receptor affinity and effector cell biology.

Professor James Spicer, professor of experimental cancer medicine at King’s College London, consultant in medical oncology at Guy’s and St Thomas’ NHS Foundation Trust and the study’s lead investigator, said: ‘IgE is a completely new form of antibody therapy which has shown great promise in this phase I trial. Our findings show that the drug was well tolerated in patients and shrunk a cancerous tumour in a patient with ovarian cancer.

‘The results pave the way to development of an entirely new class of anti-cancer drug for people with chemotherapy-resistant cancers. The immunology expertise in King’s College London laboratories allowed us to undertake this trial of a completely new form of antibody therapy.‘