Snippet roundup: Fibrogen's Japanese hit and Madrigal's smash in Nash

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Welcome to your weekly roundup of EP Vantage’s snippets – short takes on smaller news items.

This week, May 28-June 1, 2018, we had thoughts on the following: Japan readout marks start of a nervous wait for Fibrogen; Clearside’s eye prospects no longer so clear; Madrigal’s turn in the Nash spotlight; oral sema beats Jardiance, but weightier tests remain; Myriad opts in to NIPT.   

These snippets were previously published daily via twitter.

Japan readout marks start of a nervous wait for Fibrogen

1 June, 2018

Another success in Japan with roxadustat means that Fibrogen investors now have a nervous wait for readout of this anaemia project’s massive, 9,000-patient programme designed for western approval. This was recently delayed by six months, and is now expected to yield data in the fourth quarter and lead to a US filing next year. A Japan application is to be made later in 2018. The Japanese trial reported yesterday concerned 303 dialysis-dependent chronic kidney disease patients already treated with Aranesp, and showed non-inferiority to Aranesp in terms of maintaining haemoglobin levels at weeks 18-24. Four pivotal trials are ongoing in the west in dialysis-dependent subjects, and the two most akin to the Japanese study just reported are Sierras and Pyrenees: these compare roxadustat versus Epogen or Aranesp, and as primary endpoint measure change in haemoglobin, though at weeks 28-52. An earlier trial showing non-inferiority – and numerical superiority – to Epogen led to roxadustat being filed in China. EvaluatePharma sellside consensus sees roxadustat generating $269m of royalties for Fibrogen – the asset is licensed to Astrazeneca and Astellas – and the Japanese success could further allay investors’ worst fears.

Clearside’s eye prospects no longer so clear

1 June, 2018

Clearside Biomedical’s corticosteroid eye injection CLS-TA is no better than Regeneron and Sanofi’s Eylea in diabetic macular oedema, and is linked with a higher risk of cataracts. This was the conclusion of the phase II Tybee trial, the results of which sent Clearside’s stock down 32% yesterday. Perhaps there are fears that adverse events – the study also found a higher incidence of intraocular pressure – could hold back use in CLS-TA’s lead indication of uveitis, where it posted a phase III win in March. CLS-TA is also in two pivotal trials in retinal vein occlusion, and the latest data might have sown some doubts about their chances – like Tybee, Sapphire is evaluating CLS-TA alongside Eylea, while Topaz is looking at a combo with the anti-VEGF agents Lucentis or Avastin. Regeneron has itself run into problems when seeking to show a benefit with combinations over Eylea monotherapy, but this will be no consolation to Clearside. The smaller company claimed that Tybee was a success by showing noninferiority to Eylea alone, but with less frequent dosing – but with Regeneron’s drug expecting a decision in August on quarterly dosing, new challengers will need to do better than that.

Madrigal’s turn in the Nash spotlight

31 May, 2018

Remember Nash? It might be back, thanks to new data from a phase II trial of Madrigal Pharmaceuticals’ MGL-3196 that showed significant improvements in Nash activity score and resolution versus placebo. Madrigal had already reported positive imaging data from the same study at 12 weeks, but today’s 36-week readout adds data from end-of-study liver biopsies, a harder endpoint. Among the 73 patients treated with MGL-3196 who underwent a liver biopsy, 56% had a two-point reduction in Nash activity score and 27% saw Nash resolution, compared with 32% and 6% respectively in the placebo group. The response was even better in patients who saw a reduction in liver fat at the 12-week endpoint – which could give Madrigal a greater chance of phase III success if it can home in on the subgroup most likely to benefit, as well as potentially helping regulators and payers. The main adverse event was mild diarrhoea, which should come as some relief as the mechanism of action, thyroid hormone receptor (THR) agonism, has been linked to cardiotoxicity. Madrigal’s shares jumped 73% in early trading today, while another company working in THR modulation, Viking Therapeutics, rose 79%. Shares in the Nash leaders Intercept and Genfit were down 5% and 4%, respectively.

Oral sema beats Jardiance, but weightier tests remain

30 May, 2018

Novo Nordisk’s key growth driver, its oral version of semaglutide, has passed an important test in its first head-to-head trial against an established diabetes drug, but more big readouts await. And mixed data on weight loss in the Pioneer 2 study, which tested oral sema, a GLP1 agonist, against Lilly and Boehringer Ingelheim’s SGLT2 inhibitor Jardiance, appear to have made investors jittery – Novo shares opened down 1% this morning. Still, Pioneer 2 met its primary endpoint with oral sema significantly lowering blood glucose compared with Jardiance. Novo’s drug reduced HbA1c by 1.4% at 26 weeks versus a 0.9% reduction with Jardiance. While oral sema did not significantly lower weight  versus Jardiance at 26 weeks, it did manage to do so at one year. A higher discontinuation rate with oral sema might also have made investors nervous, particularly as nausea looked more problematic than in previous studies. Investors will hope for more emphatic weight-loss data in the all-important Pioneer 4 study testing oral sema against Novo’s older GLP-1 agonist Victoza; results are due this quarter. Novo has said that as sema crosses the blood-brain barrier more easily it should have a bigger effect on appetite.

Myriad opts in to NIPT

29 May, 2018

Buying Counsyl for $375m in cash and stock has allowed Myriad Genetics to get a slice of the fast-growing but closely contested non-invasive prenatal testing (NIPT) and genetic carrier testing markets. Counsyl sells Foresight, a test used to screen prospective parents to determine whether they carry genes for more than 175 genetic conditions including cystic fibrosis, and a NIPT product, Prelude, designed to test foetal DNA in the mother’s blood for chromosomal abnormalities including Down’s syndrome. Myriad’s hereditary cancer testing, its traditional core business, is forecast to shrink 3% out to 2024, and teh group is largely reliant on GeneSight, its genetic panel to assess patients’ likely response to drugs for mental illnesses, to make up the shortfall. But a recent attempt to maximise the value of GeneSight, by persuading payers to reimburse it at $2,000 rather than the current level of $120, appears doomed after use of the test to guide therapy did not improve depression patients’ symptoms in a trial that reported last year. Counsyl had sales of $134m last year, and Leerink analysts estimate that it was growing at around 30% year-on-year. And this could continue, especially since the American College of Obstetricians and Gynecologists might broaden its guidelines to recommend NIPT for average-risk women.

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