Lucentis (ranibizumab) was developed by Roche subsidiary Genentech. Last November Novartis, which owns the rights outside the US, submitted an application to the World Health Organisation (WHO) to include the monoclonal antibody on its list of essential medicines for the treatment of the vision loss disease wet age-related macular degeneration (AMD).
But last week the WHO rejected the application, opting instead for the ophthalmological preparation of fellow Roche monoclonal antibody Avastin (bevacizumab) which, despite not being approved to treat ocular conditions, has been used used off-label to treat wet AMD at a much lower cost.
The two drugs have been found to be equivalent in action in treating the disease, but according to a WHO committee report, a 3mg vial of Lucentis containing one dose costs £761 ($1,200) while a 100mg vial of Avastin can be compounded into ten doses at a cost of just £24 – 31 times less.
But the problem lies with the need to use a third-party compounder. There have been a number of safety problems surrounding lack of GMP and lack of regulation among compounding pharmacies, culminating in the death of over 60 people from fungal meningitis in 2012, traced back to one particular company.
“We had a number of discussions with payers with regard to these kinds of issues and one of the biggest challenges with compounding Avastin is the safety issue,” said Bertrand Liang, CEO of Pfenex, which is developing a biosimilar version of Lucentis.
Discussing his firm’s first quarter results last week, Liang admitted there will always be some physicians who will continue to prescribe Avastin instead of Lucentis, but “if a biosimilar Lucentis was available, that would be presumably at a discount to the innovator product, and that’s going to be much more accepted than potentially having to compound Avastin.”
The US Food and Drug Administration (FDA) has started to regulate compounding pharmacies, allowing them to register as contract manufacturing organisations (CMOs) and publishing some guidance, but rather than encouraging off-label use, Liang believes this may hamper Avastin in this disease area.
“We’re beginning to see that the level of acceptability of compounding Avastin is going to be constrained much more on the side of just making sure that it’s a safe thing to do,” he told stakeholders.
“I think Lucentis biosimilar is actually going to help with the process in order to get acceptability of something that is actually not going to be compounded and yet has a presumed price discount to an innovative product.”
Pfenex’s biosimilar candidate is PF582, and the company received an upfront payment of $51m in the quarter from Hospira which signed a collaboration agreement in February.
Pfenex is using its Pfenex Expression Technology based on automated high-throughput screening of large libraries of genetically engineered Pseudomonas fluorescens bacterial expression strains to produce the mAb and, if successful, is eligible to receive up to $291m in milestone payments along with double-digit royalties from Hospira.
“The collaboration is going well and we continue to assist in the manufacturing technology transfer of PF582 in cooperation for the comparable clinical trial to begin in 2016,” Liang said.
(The WHO's 2015 list of essentials medicine can be found here.)