Welcome to your weekly digest of approaching regulatory and clinical readouts. In June data are due from a phase II trial testing Acceleron’s dalantercept, an ALK 1 inhibitor, in renal cancer. Immunotherapies are beginning to make a mark in this disease, perhaps leaving newcomers on the back foot.
Also the FDA will decide by June 9 whether to approve Coherus Biosciences’ CHS-1701, which could become the first Neulasta biosimilar to market, though ongoing litigation could delay entry.
The phase II Dart study tests dalantercept in combination with Pfizer’s Inlyta in advanced renal cell cancer.
Its first part was a dose escalation looking at safety and tolerability, with data reported at Asco in 2015. Dalantercept given at 0.6mg/kg, 0.9mg/kg or 1.2mg/kg plus twice-daily Inlyta led to an objective response rate (ORR) of 25% and median progression-free survival (PFS) of 8.3 months for all doses combined.
The imminent data are from Dart's second part. Here, 0.9mg/kg dalantercept was given subcutaneously once every three weeks, plus 5mg of oral Inlyta twice daily. The comparison is against placebo plus Inlyta.
Part two enrolled 130 subjects who had progressed after treatment with a VEGF receptor tyrosine kinase inhibitor, and they may have also had mTOR or immune therapy. The primary endpoint is PFS at six months; secondary measures include overall survival and ORR.
Inlyta is standard of care in second-line treatment, and has previously demonstrated five-month PFS in renal cancer, Leerink analysts say. Dart is powered to show a 50% increase, to approximately 7.5 months.
Consensus forecasts for dalantercept sit at $357m, with Acceleron expecting to look for a partner before phase III. Celgene is partnered on its most advanced asset, luspatercept, which is now in pivotal trials in myelodysplastic syndromes and beta-thalassemia.
The renal cell carcinoma space is competitive, and Sutent dominates first-line treatment. In second line Opdivo is the preferred choice, followed by Cabometyx, according to Leerink. Opdivo has shown a median OS of 25 months versus 19.6 months for Afinitor in second line, and Cabometyx resulted in 21.4 months versus 16.5 months – so even if dalantercept succeeds, it might have a hard time competing (Therapy focus – New kidney cancer data emerge in time for Asco, May 24, 2016).
CHS-1701 is Coherus’s biosimilar version of Amgen’s Neulasta (pegfilgrastim), and has an FDA action date of June 9 for preventing neutropenia in patients undergoing chemotherapy.
It could become the first Neulasta biosimilar on the market early next year, but could be launched sooner if the US Supreme Court overturns a 180-day notification period; a decision could also come in June.
To try and stave off entry Amgen recently sued Coherus over an infringement of its ‘707 patent, which covers purification of the drug and expires in 2024; a couple of months ago Amgen also filed a trade secrets lawsuit. The complaint links former Amgen employees now working at Coherus with alleged breaches in confidentiality agreements regarding Amgen’s pipeline. Coherus rejected the claims.
Coherus reported a positive bioequivalence study with ’1701 last July, comparing 6mg of CHS-1701 versus 6mg of Neulasta. This met all of its co-primary endpoints in healthy subjects, and ’1701 had a similar safety profile to Neulasta. Efficacy was not a requirement of the trial.
Neulasta had sales of $4.8bn last year, but this is expected to almost halve by 2022 to $2.8bn, according to sellside consensus from EvaluatePharma. Sales of CHS-1701 are forecast to reach $648m by 2022, at which point it will be Coherus’s top-selling product.
On the competitor front Mylan’s own biosimilar, MYL-1401H, is closest behind Coherus, with an FDA decision due in October. Meanwhile, Apotex was recently granted an inter partes review over a patent regarding protein folding. Novartis's Sandoz unit received a complete response letter for its biosimilar last July, and pulled a European application earlier this year.
|Neulasta market and late stage biosimilars|
|Global sales ($m)|
|Marketed||Neulasta||Amgen||4,648||2,553||WW ex-Japan, South Korea, Malaysia, Singapore, Taiwan, Thailand & Vietnam; Greece (royalties)|
|Neulasta||Kyowa Hakko Kirin||143||206||Japan, South Korea, Malaysia, Singapore, Taiwan, Thailand & Vietnam|
|Filed (all biosimilars)||CHS-1701||Coherus BioSciences||-||616||WW ex-Caribbean & L America ex Brazil (royalties)|
|MYL-1401H||Mylan/Biocon||-||151||US, Canada, Japan, Australia, New Zealand & Europe (profit share); RoW (co-promotion)|
|CHS-1701||Undisclosed partner sales||-||32||WW ex-US|
|Lapelga||Apotex/Intas Pharmaceuticals||-||-||US, Europe & Canada (Intas royalties)|