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PIM status for Boehringer’s mesothelioma drug

Boehringer Ingelheim’s nintedanib has been designated a Promising Innovative Medicine for the treatment of malignant pleural mesothelioma (MPM) by the UK Medicine and Healthcare Products Regulatory Agency.
This indicates that the regulator considers nintedanib is promising candidate for the UK’s Early Access to Medicines Scheme, which gives patients with life threatening or seriously debilitating conditions access to medicines before they are approved for use in Europe.
“This is fantastic news and the right decision taking into account the risk/benefit profile of nintedanib from a very credible Phase II trial,” said Professor Dean Fennell, Chair of Thoracic Medical Oncology at the University of Leicester and University Hospitals of Leicester NHS Trust, UK, commenting on the decision.
MPM is a relatively rare but aggressive thoracic cancer that is often rapidly progressive once clinically apparent, most cases of which are linked to long-term exposure to asbestos.
In 2014 there were 2,502 cases of MPM in the UK, and patients have a poor prognosis, with median survival ranging from eight -14 months from diagnosis.
For patients with unresectable disease, first-line combination doublet chemotherapy treatment with cisplatin or carboplatin and pemetrexed has been the standard of care for more than 10 years. However, this “has been limited to a progression-free survival (PFS) not getting beyond six months,” according to Professor Fennell.
He also noted that with regards to overall survival (OS), “more trials are needed in relapsed patients, where there is no standard of care in the second-line setting.”
Nintedanib’s PIM status was awarded on the back of non-clinical and clinical data including that from the Phase II LUME-Meso Trial, which showed statistically significant improvements in PFS in patients with MPM treated with the drug plus chemotherapy (9.4 months) compared to those receiving chemotherapy alone (4.7 months).
Results also showed a trend towards an overall survival benefit (a secondary endpoint) with nintedanib, with a 4.1 month improvement for patients treated with the drug plus chemotherapy versus chemotherapy along (18.3 months vs 14.2 months, respectively), though this did not reach statistical significant, BI said.
The drug is now being assessed in the Phase III LUME-Meso trial, which is currently recruiting MPM patients at trial sites worldwide, including five in the UK.
Nintedanib is an oral triple angiokinase inhibitor that targets receptors for three growth factors (VEGF, FGF and PGF), as well as Src and Abl signalling, which are implicated in the development of MPM.
The drug is marketed as Vargatef for use in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) or of adenocarcinoma tumour histology after first-line chemotherapy. It is also approved to treat the lung-scarring disease idiopathic pulmonary fibrosis under the trade name Ofev.
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