AXIM has encapsulated hemp oil (CBD) and the psychoactive-substance tetrahydrocannabinol (THC) from the Cannabis sativa plant into mint-flavoured chewing gums as an analgesic for chronic diseases, including Multiple sclerosis and IBS.
The firm already has an ongoing Phase II trials for MS in the Netherlands for its CBD and THC containing gum MedChew. A second product – CanChewPlus – is the firm’s latest CBD-only gum, which in two weeks’ time will start a 40-patient trial for IBS at the University of Wageningen, Netherlands.
in-PharmaTechnologist asked George Anastassov and Lekhram Changoer, Chief executive and chief technology officers of AXIM Biotechnologies about the manufacturing and regulatory challenges involved in developing its candidates.
Are there any safety concerns using the psychoactive substance THC in a chewing gum?
Lekhram explained that in the trial for IBS, up to 6 gum pieces of CanChewPlus will be given to each patient per day, equal to around 300mg CBD (based on average weight of patient being 50Kg).
Anastassov told us “Doses between 10 and 20mg per kg per day of CBD are safe,” and that the lead product from another CBD focused firm, UK-based GW Pharmaceuticals, is using similar doses to treat rare forms of Epilepsy.
“If our IBS trial goes as planned and proves the concept, we will also expand the CanChewRx CBD-based programme development for other GI indications such as UC and Crohn’s disease.”
Can you explain the bioavailability a bit more regarding breakdown of excipients, and release of APIs?
Anastassov: “That’s the unique side to our gum’s IP. Since cannabinoids are highly hydrophobic and lipophilic, in development they were adhering too much to the gum base and not being released properly.”
Even after chewing for over 1 hour of a regular gum with CBD, Anstassov explained more than 50% of the API remained in the gum due to binding of the CBD-oil with the gum base.
This also meant that some patients with temporo-mandibular joint disorder might have trouble chewing the gum over a long period, which would have exacerbated their disease.
“With CanChewPlus, we believe we have solved this problem, and the APIs are fully released in 20 minutes or so.”
How are the active pharmaceutical ingredients incorporated into the chewing gum?
For oral delivery of the APIs, a compressed gum base is supplied by the ingredient supplier Cafosa in Barcelona, Spain.
The gum base serves as a platform material to microencapsulate its CBD/THC formulation, which AXIM does using a spray technique in liquid nitrogen.
“We have developed some IP on this microencapsulation technology, as pure forms of THC (99.9%) are highly unstable due to oxidation on room air and subsequent auto-catabolisation,” explained Lekhram.
“The low temperature is critical in maintaining an environment that prevents oxidation of the formulation, and after spraying, a synthetic polymer is used to protect and encapsulate the system.”
What production capacity do you currently have?
“As far as capacity, we’re still in our clinical trial phase – which is producing small batches of product and placebo,” said Lekhram.
“Once the products are approved, the capacity will be 10,000+ Kg on the batch size for commercial production.”
Does AXIM have any contract research organisations (CROs) partners?
AXIM previously told in-PharmaTechnologist it was partnered with the Dutch CRO Syncom and Danish contract manufacturer Fertin Pharma A/S.
However, Lekhram added it is now partnered with QUAY Pharma, a contract manufacturer in the UK for the microencapsulation process, and the Delaware-based CRO QPS, which has a unit in Groningen that offers Toxicology, DMPK and Neruopharmacological services.
AXIM has also acquired land to build its own GMP-compliant manufacturing facility in the Netherlands near Almere, which is under development.
Anastassov added “Although Medical Marijuana, Inc. is a significant investor, the firm does not have a decision-making capacity in AXIM.”
Other indications being addressed?
Anastassov explained that AXIM is looking to treat various other indications with its cannabinoid range of gums, with a particular interest in neurodegenerative diseases.
“We started the company to introduce a novel class of analgesics, and found that both CBD, CBG and THC are particularly effective in treating chronic, neuropathic conditions.”
For example, for post-herpetic neuralgia the firm is using gabapentine with cannabinoids, and for dermatological diseases like Eczema and psoriasis it is developing a topical delivery system using Cannabigerol (CBG) and CBD, as well as its controlled release chewing gum.
“We are also waiting for approval from Health Canada for a trial in patients with drug-related psychosis – to take place at the University of British Columbia, Vancouver.”
When does AXIM hope to submit a New drug application if the Phase III trial for Multiple Sclerosis goes well?
AXIM expects to report the Phase II results of 5mgTHC/5mgCBD gum for pain and spasticity in Multiple Sclerosis by the Q2 or Q3 this year.
Anastassov added “If successful, we will immediately move into Phase III of the clinical trial, with submission of an NDA either the end of this year or beginning of 2017.”