Welcome to your weekly digest of approaching regulatory and clinical readouts. AstraZeneca should find out soon if it will be successful in its “orphan first” strategy for getting the Mek inhibitor selumetinib to the market as readout is due for a phase III trial in uveal melanoma.
KaloBios, meanwhile, needs to hope that it can bounce back from numerous setbacks with positive data in haematological malignancies for KB004. The California-based group needs to show that its technology platform for developing low-immunogenicity antibodies can yield projects that work in the clinic.
Climbing to the Sumit
Selumetinib was licensed from Array BioPharma, and had been positioned broadly for melanoma. However, the space is already crowded with Novartis’s own Mek inhibitor Mekinist having been on the market since 2013, and Roche’s cobimetinib queueing up to follow, perhaps later this year.
Astra appears to have largely downplayed most of its efforts in melanoma and made a big push in second-line KRAS-mutant non-small cell lung cancer. However, earlier this year the group achieved FDA orphan designation in metastatic uveal melanoma, which although rare is the most common primary cancer of the eye – in the US 4,070 cases were recorded between 1973 and 2008, or about 35 a year.
Thus a positive readout in the Sumit trial would lead to a swift approval. Astra expects to file for registration this year.
The Sumit trial pits selumetinib and dacarbazine against dacarbazine alone in 152 patients, with progression free survival as the main endpoint. An open label phase II trial found that selumetinib as a monotherapy significantly extended progression free survival, to a median of 15.9 weeks, compared with seven weeks for patients treated with temozolomide, although no difference in overall survival was detected.
Nearly all the patients treated with selumetinib experienced an adverse event, with 37% requiring at least one dose reduction.
A failure to show an overall survival advantage in phase III will probably not stand in the way of approval for an orphan indication, and neither will a high adverse event rate.
Selumetinib is forecast to achieve $268m in 2020 sales, nearly all of which will be accounted for by the lung cancer indication. But in looking to launch it as an orphan drug first, Astra is following a time-tested strategy that should at a minimum get selumetinib to the market with minimal inconvenience, before expanding to bigger prizes later.
Try, try, and try again
In the midst of the biotech boom KaloBios has failed to thrive. Cancellation of asthma and Pseudomonas aeruginosa projects last year caused shares to collapse, followed by the departure of its chief executive, David Pritchard, early this year.
With an executive chairman appointed and a reverse stock split executed this week, KaloBios appears to be trying to mend itself. Having some sort of success for its technology platform, dubbed “Humaneered”, would go a long way to improving expectations. The group believes that its technology allows it to produce antibodies with low immunogenicity and greater affinity.
KB004 is being tested in a phase I/II trial to determine a maximum tolerated dose and assess clinical activity in patients with acute myeloid leukaemia, myelodysplastic syndrome and myelofibrosis. Patients will be screened for tumour cells expressing EphA3 receptors, which KB004 blocks.
The company has said it expects to announce topline results from the leukaemia and myelodysplastic syndrome patients in mid-2015. Signs of activity against the haematological diseases could see it return to favour, perhaps enlivening its tiny $11m market cap.
Another failure might not damage it any further, but it could spur the group to take a longer look at a technology that so far has produced nothing of clinical value.