The Booming Business of Neurotoxin Therapy
Industry Insight Feb 06, 2019 | by Ruairi J Mackenzie, Science Writer for Technology Networks
A photomicrograph of Clostridium botulinum bacteria, which produces botulinum neurotoxin. Credit: Content Providers: CDC [Public domain], via Wikimedia Commons
During last month’s TOXINS 2019 conference in Copenhagen, Ipsen revealed the results of their first in-human trial assessing the safety and tolerability of its rBoNT-E compound, a recombinant neurotoxin based on the botulinum toxin serotype E.
Naturally produced by the bacteria Clostridium botulinum, botulinum neurotoxins are widely used in both therapeutic and cosmetic applications, but Ipsen says that rBoNT-E is a step up in several departments from compounds based on the much more widely used serotype A toxin. We spoke to Ipsen Senior Vice President Neurosciences R&D, Philippe Picaut, to find out more.
Ruairi Mackenzie (RM): “Neurotoxin” is a rather intimidating term, but botulinum toxin (BoNT) treatments have been widely accepted for use, even in cosmetic applications. What has the industry done to successfully communicate the safety and efficacy of these treatments?
Philippe Picaut (PP): Currently, botulinum toxins are well known and accepted for therapeutic and aesthetic indications. Actually, these toxins have been widely studied as they show very interesting properties – they temporarily block release of acetylcholine leading to muscle relaxation. The first usages of botulinum toxins, in the 1980s, were treatments of strabismus and blepharospasm. Nowadays, botulinum toxins have many therapeutic (e.g. adult and children limb spasticity, cervical dystonia, hyperhidrosis…) and aesthetic indications. With Dysport®, Ipsen has 30 years of clinical experience. Dysport®’s efficacy and safety have been assessed in studies and we are still exploring its potential.
Botulinum toxins are prescribed treatments. This is why, at Ipsen, we also provide medical education and injection trainings to physicians, for an optimal use of Dysport®.
RM: What are the currently available botulinum products?
PP: Seven natural serotypes of botulinum toxin exist, and the commercialized products are mainly type A. Dysport®, from Ipsen, was first approved on 06 Dec 1990, in the UK.
Currently, Dysport® has proven benefits for 7 therapeutic and 2 aesthetic indications. We continue investing in Dysport® through research and clinical studies to further investigate its potential and address patients’ unmet needs. Two Phase 2 studies in new indications, for Hallux valgus (bunions) and vulvodynia (chronic vulval pain) have started in 2018 with readouts in about one year.
RM: How does Ipsen’s rBoNT-E compare to other available botulinum-based products? What were the results of your recent phase-I study into rBoNT-E?
PP: Ipsen have just published the results from the phase 1 clinical trial with recombinant BoNT-E at the international TOXINS conference. For this first-in-human study conducted in the UK, the objective was to collect preliminary safety and pharmacodynamic information on our type E recombinant toxin. In addition, it aimed to provide perspective on the efficacious and safe doses of rBoNT-E following a single injection in the extensor digitorum brevis (EDB) muscle of healthy male subjects.
Our results demonstrated a differentiation of rBoNT-E with Dysport®:
- A faster onset of action
- A quicker time to maximal effect
- A greater peak effect
- A shorter duration of action
In conclusion, recombinant BoNT-E is a fast-acting toxin which opens the door to a new treatment paradigm for patients. Further studies will be conducted by Ipsen to establish potential therapeutic and aesthetic uses of this fast-acting toxin.
RM: Were there any adverse events related to the use of rBoNT-E seen in the study?
PP: rBoNT-E was administered as a single intramuscular injection at doses up to 3.6ng and it did not display any unexpected treatment-related adverse events.
RM: What are the next steps and potential applications for rBoNT-E?
PP: New technologies such as recombinant expression technology are now enabling the manufacture of neurotoxins identical to those found in nature as well as novel ones with increased therapeutic potential. Recombinant toxins could provide many benefits such as a broader range of indications treatable with a suite of specifically engineered BoNTs or simpler dosing for physicians.
Concerning rBoNT-E, Ipsen shared the results from the phase 1 study with the scientific community at TOXINS conference. We target to enter into phase 2 this year in therapeutic and aesthetic to characterize its clinical safety and efficacy in patients. Preliminary results are expected in 2020.
Phillippe Picaut was speaking to Ruairi J Mackenzie, Science Writer for Technology Networks