Welcome to your weekly digest of approaching regulatory and clinical readouts. Aeterna Zentaris will be hoping it can ring in the New Year with its first US approval, but its growth hormone deficiency diagnostic Macrilen has been rejected before, and its confirmatory trial missed expectations. The company’s shares have been decimated over the years, and it desperately needs a win.
Pharmamar will see results from the first phase III trial of Zepsyre, a transcription inhibitor, in ovarian cancer early next year. Zepsyre is the company’s lead growth driver and could supersede the ageing drug Yondelis.
Aeterna Zentaris is making a second attempt at US approval for Macrilen, intended to diagnose adult growth hormone deficiency, which is due a response from the FDA by December 30.
The company has had a tumultuous few years. A complete response letter for Macrilen three years ago caused its shares to tumble nearly 50%, and setbacks with a number of its other products mean its valuation is now just $36m.
The CRL detailed efficacy and safety concerns – there was a serious event of QT interval prolongation. Aeterna subsequently performed a confirmatory phase III study that used the insulin tolerance test (ITT) as a comparator. However, data from the two-way crossover trial were mixed, with Macrilen failed to show equivalence to ITT.
Still, there were some crumbs of hope for Aeterna. The trial had a co-primary endpoint of percent positive and percent negative agreement, similar to sensitivity and specificity, between the two tests. The estimated percent negative agreement met the success criteria but the estimated percent positive agreement did not. There was no mention of any safety concerns in the trial.
Despite the mixed data the company ploughed on with the filing, which the FDA accepted in July. Currently there is no FDA-approved test to diagnose adult growth hormone deficiency and ITT has many contraindications. ITT also requires close supervision as it can potentially send the patient into a diabetic coma.
With just $12.2m in cash Aeterna will be hoping that the FDA might look more favourably on its project this time round.
|Confirmatory phase III||NCT02558829|
Pharmamar’s phase III
Pharmamar, meanwhile, will hope for a better result in its phase III Corail trial of Zepsyre, previously known as lurbinectedin, in 443 patients with platinum-resistant ovarian cancer. Zepsyre, given intravenously at a dose of 3.2mg/m
The primary endpoint is progression-free survival at 48 months, with overall survival and overall response rate included as secondary measures. The study is 90% powered to detect a hazard ratio of 0.7, and data are due early in the first quarter of 2018.
In the randomised, controlled stage of an 81-patient phase II trial, Zepsyre showed a statistically significant PFS benefit of 5.7 months versus 1.7 months for Topotecan (p=0.005). The most common side-effect was neutropaenia, with grade 3/4 in 85% of patients. The phase II study used a flat dose of 7mg of Zepsyre; the phase III trial was amended to take into account body surface area due to the high levels of neutropaenia.
The drug works by inhibiting RNA II polymerase transcription, making it similar to the company’s Yondelis, which has been on the market for 10 years. Zepsyre is expected to be Pharmamar’s lead growth driver with 2022 sales forecasts at $401m, according to EvaluatePharma sellside consensus.
Zepsyre is also in phase III for small cell lung cancer with data due by mid 2019, and pivotal studies are also expected to start next year in breast cancer and endometrial cancer.
Yondelis, meanwhile, is expected to bring in $144m for Pharmamar in 2022, with Johnson & Johnson picking up $164m outside of Europe. In the US Yondelis is on the market for soft tissue sarcoma, and in Europe it also has ovarian cancer on the label. J&J has an ongoing phase III study with Yondelis in platinum-sensitive ovarian cancer, and US approval could come in 2019 or 2020.
Pharmamar, based in Madrid, doesn’t yet have a US partner for Zepsyre. Stifel analysts note that successful data could be a prelude to a potential Nasdaq IPO to raise the funds to build a US infrastructure to commercialise the drug.