Upcoming events – Readouts approach for Cerulean and BioCryst

Welcome to your weekly digest of approaching regulatory and clinical readouts. Cerulean is hoping to follow promising data published earlier this year for CRLX101 with a similar showing in kidney and ovarian cancers.

BioCryst, meanwhile, needs some positive late-stage results from its lead hereditary angioedema project, which could become the first oral agent to prevent acute episodes of the rare condition.

Cerulean: CRLX101

Cerulean Pharma is on track to report phase II data for its lead candidate, the nanoparticle drug conjugate CRLX101, in combination trials for metastatic renal cancer in the first half of 2016 and in ovarian cancer before the end of 2015.

CRLX101’s trial in its lead indication, metastatic renal cell carcinoma, for which it has received FDA fast-track designation, is set to read out in the second quarter of 2016. The trial comprises 110 second or third-line patients being treated in combination with Avastin, with a primary endpoint of progression-free survival (PFS), versus the current standard of care treatment.

The outlook seems good for CRLX101 if it can follow up on the impressive interim results presented at Asco this year, which showed a 6.4-month improvement in PFS over the standard of care. There are few options to treat advanced renal cancer and a sparse-looking industry pipeline for the indication (Therapeutic focus – Opdivo and Cometriq tussle in kidney cancer, October 5, 2015).

More immediate are the results for the investigator-sponsored trial in recurrent platinum-resistant ovarian cancer due by the end of the year. CRLX101 also shows promise in this indication, having received orphan drug designation, following results of a monotherapy trial presented in May. Once again, the project is being studied in combination with Avastin, with the primary endpoint being PFS, this time without a comparator arm.

Edison analysts forecast peak sales for CRLX101 of $490m and $340m in metastatic renal and ovarian cancer respectively when combined with Avastin.

BioCryst: avoralstat

Peripatetic BioCryst Pharmaceuticals – its focus has jumped from gout to hepatitis C in recent years – now has an important readout approaching in its hereditary angioedema (HAE) project avoralstat, previously coded BCX4161.

The phase II/III Opus-2 trial, data from which are expected in early 2016, tests the oral kallikrein inhibitor against placebo in the prevention setting, where it will be up against the intravenous drugs Cinryze from Shire and Ruconest from Valeant and Pharming. The study will measure the angioedema attack rate over 12 weeks as a primary measure, with attack-free days, disease activity and severity of attacks among the secondary endpoints.

A one-month phase IIa trial with a crossover design found a statistically significant reduction in the attack rate – 0.82 per week versus 1.27 – for avoralstat (BioCryst pushes positive HAE news and taps market once again, May 29, 2014). The latest study does not have a crossover design but tests two doses, 300mg or 500mg three times daily, against placebo.

Sellside analysts have given fairly generous sales forecasts to the project, with EvaluatePharma’s consensus coming at $246m in 2020 – a level Cinryze reached in its third year on the market. As an oral alternative avoralstat could be more attractive to patients, even if at the 500mg dose they will have to take 15 pills a day.

A win in this trial would be vital to proving that BioCryst's drug design programme can be successful. A once-daily HAE pill called BCX7353 has just completed phase I trials in healthy patients and is moving into phase II in HAE patients in late 2015 or early 2016.

Success might also be necessary to BioCryst’s potential as a takeout. Shire looks unlikely to buy, having built a fairly strong HAE franchise, strengthened even further by its acquisition of Dyax for its preventive kallikrein-inhibiting antibody lanadelumab.

With Shire passing on the oral option so far, Valeant, which picked up Ruconest rights as part of its Salix buyout, would be the only plausible acquirer with a presence in this space. As Valeant is facing some other pressures, BioCryst might want to get used to pushing on alone.

Project Study Trial ID
CRLX101 Ovarian cancer NCT01652079
Renal cell carcinoma NCT02187302
Avoralstat Opus-2 NCT02303626

To contact the writers of this story email Edwin Elmhirst or Jonathan Gardner in London at news@epvantage.com or follow @EPVantage or @ByJonGardner on Twitter

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