Until now, topical biologics have been unpopular among developers because of permeation problems. But advances in technology and a push to stay competitive as patents expire have led drugmakers to identify new delivery methods, according to contract research organisations Kemwell and Tergus Pharma.
Zaps, patches and sprays
Companies have begun disrupting the skin’s barrier artificially or tackling diseases where the epidermis is already damaged. Zecuity, the migraine patch acquired by Teva when it bought NuPathe in January, falls in the former category. The topical treatment delivers sumatriptan – a drug otherwise too large to penetrate the skin – using a low electrical current powered by lithium batteries in a process called iontophoresis.
Other firms are trying patches studded with painless microneedles – a little like Velcro – to pierce the skin and deliver biopharmaceuticals.
Nasal mucosa (not to be confused with nasal inhalation) are another area for local delivery – like the spray delivery of the hormonal peptide oxytocin in children with autism, which found success in a study by the National Institute of Child Health and Human Development and the University of North Carolina. The delivery method requires less frequent doses of oxytocin, which has a half-life of only three minutes via injection and is destroyed in the GI tract.
Elsewhere, indications where the skin barrier is already compromised – like psoriasis or wound healing – are proving a good fit for local delivery of biologics.
There are still challenges: local enzymes can destabilise proteins, and there is a limit to molecule size, Vijendra Nalamothu, CEO, Tergus, told Biopharma-Reporter.com. Topical creams work with proteins and peptides that are “not huge – you’re looking at 7,000 Da.”
Thanks to penetration enhancing excipients these creams can be rubbed in manually but need very special manufacturing to handle their proteins, Nalamothu told this reporter at this year’s meeting of the American Association of Pharmaceutical Scientists in San Diego.
Heat and pressure are avoided during production as they can denature the protein.
The typical method of manufacturing creams – with high shear homogenisers to mix oil and water – is also out. Instead, companies dissolve proteins in a solution before adding it to the cream base, followed by a stabiliser to prevent separation.
Ninad Deshpanday, head of R&D at Kemwell, confirmed his company is seeing a renewed interest in topical biologics – both because of an increase in drug candidates and in new technologies. He stressed that for now any breakthroughs will be for local, not systemic diseases – skin cancer is a popular target.
Biopharma organisations keen to start delivering their products typically will have to work around regulatory hurdles. Agencies require local drugs – whether large or small – to leap specific irritation and toxicity hurdles. Biologics considered safe in oral or injectable form will need to demonstrate topical safety over the long exposures typical of chronic skin indications.