Welcome to your weekly digest of approaching regulatory and clinical readouts. By early October Mylan and Biocon will see whether their pegfilgrastim can become the first approved Neulasta biosimilar in the US. However, manufacturing issues have scuppered it in Europe, and could hit it similarly across the pond.
Also Aerie’s Rhopressa will come before a US advisory panel on October 13. It only managed to pass phase III thanks to an endpoint change and is associated with substantial adverse events, meaning that it has a tough job to convince the regulators.
First to market?
An FDA approval date is set for October 9 for Mylan and Biocon’s pegfilgrastim, a biosimilar of Amgen’s Neulasta, used to treat neutropenia in patients with non-myeloid malignancies.
Earlier this year as part of an EU filing an inspection of Biocon’s manufacturing facilities in Bangalore found 35 deficiencies including 11 that were major, causing the regulator to issue a statement of non-compliance. With the need for re-inspection the European filing was withdrawn last month, and the FDA will undoubtedly note these concerns.
Manufacturing aside, getting Neulasta biosimilars past the FDA has proven incredibly tricky. In June Coherus received a complete response letter, with the FDA requesting re-analysis of samples of its biosimilar CHS-1701 with a revised immunogenicity assay, and more data on manufacturing processes (Coherus biosimilar knockback gives Amgen Neulasta on life, June 12, 2017).
Meanwhile Novartis’s Sandoz unit received a complete response letter for its biosimilar last July, and is conducting an additional pharmacokinetic study. Coherus is likely to resubmit before the end of the year, and Sandoz in 2019.
Litigation is ongoing between Sandoz and Amgen, while Apotex, which filed its biosimilar Lapelga back in 2014 but has not come before the regulators yet, was granted a petition to begin inter partes review over a patent regarding protein folding.
Worldwide sales of Mylan and Biocon’s pegfilgrastim are forecast to reach $203m by 2022, according to consensus from EvaluatePharma. For Amgen worldwide Neulasta sales are expected almost to halve by 2022. It is unlikely that any Neulasta biosimilars will be on the US market until at least the end of 2018 or early 2019, and Mylan has the tough task of trying to get there first.
|Neulasta market and late-stage biosimilars|
|Global sales ($m)|
|Neulasta||Amgen/Kyowa Hakko Kirin||4,791||4,525||3,490||2,690|
|Phase III biosimilars|
|PEG-GCSF Injection||NAL Pharma||-||-||-||-|
Meanwhile, Aerie has had a rollercoaster ride with its glaucoma project Rhopressa, which failed its first phase III study, Rocket-1, missing its non-inferiority endpoint against timolol.
The FDA then agreed to a change in the primary endpoint in Rocket-2 to consider patients with baseline intraocular pressure of 20-25mmHg rather than the previous 20-27mmHg, and that trial subsequently hit non-inferiority.
However, safety concerns could put a dampener on the project, and no doubt the FDA will play close attention to these at its advisory panel on October 13. Aerie had initially reported eye redness as the main drawback in the Rhopressa arm of Rocket-2, but 12-month safety data showed conjunctival haemorrhage, corneal deposits, blurry vision and – perhaps most worryingly – loss of vision clarity.
These adverse events occurred in 5-23% of patients (Glaucoma fans throw caution to the wind, February 18, 2016). Sellside consensus revenues sit at $235m by 2022, according to EvaluatePharma, and have tumbled since the first study failure.
Even if Rhopressa is approved by February it could come with a restrictive label, and with a clinical programme demonstrating that it is no worse at lowering intraocular pressure than timolol, a generic drug, getting it past the payers could be even trickier.