CEO Interview: Ulcerative Colitis Trial Shows Abivax's HIV Candidate Has Broader Potential
Executive Summary
Abivax Phase IIa data for its lead asset showed impressive results in ulcerative colitis. The biotech's CEO tells Scrip trials in Crohn's disease and rheumatoid arthritis will now follow.
Abivax will start trialing its novel lead compound in other anti-inflammation conditions after a Phase IIa trial showed ABX464 to be safe and effective in ulcerative colitis patients who are refractive to current therapies, including anti-TNF treatment, the French biotech's CEO told Scrip.
Orally administered ABX464 had already shown good results in a recently completed Phase II clinical trial to demonstrate it can deplete HIV reservoirs with a lasting effect of up to 60 days with little or no side effects, offering the prospect of a major advance over current HIV antiviral treatments.
Now, a relatively small Phase IIa clinical trial has validated the biotech's clam that the compound delivers impressive anti-inflammatory effects by triggering an increased expression of miR124, which is a potent anti-inflammatory microRNA.
Top-Line Data
That placebo-controlled clinical trial was conducted in 32 patients for induction treatment of moderate-to-severe ulcerative colitis (UC) refractory to anti-TNF monoclonal antibodies or corticosteroids.
"There are other inflammatory indications that we are going to tackle now, including Crohn's and rheumatoid arthritis, and that changes the profile of Abivax dramatically." - Abivax CEO
Its topline data showed ABX464 was safe, well-tolerated, and demonstrated statistically significant efficacy based on both clinical and endoscopic endpoints in this study.
Also, the onset of the therapeutic effect of ABX464 was fast, with a difference of the reduction of the partial Mayo score between ABX464 and placebo being observed at the first assessment following treatment for two weeks, which became significant (p<0.02) at eight weeks. Similarly, the difference of the reduction of the total Mayo score after eight weeks was statistically significant (p<0.03), according to Abivax.
The Mayo score and a non-invasive 9-point partial Mayo score are used as outcome measures for clinical trials assessing therapy for ulcerative colitis. The higher the score, the more severe the case of ulcerative colitis. The highest score possible is a 12. Scores should be compared with previous scores taken for a patient.
Gives New Validation
Abivax now has validation in a completely different therapeutic area where a novel therapeutic approach could do extremely well, its CEO Hartmut Ehrlich said in an interview.
"We cannot over-estimate the value of this data to Abivax. It opens up ulcerative colitis with an orally administered drug that has a brand new mechanism of action. And there are other inflammatory indications that we are going to tackle now, including Crohn's and rheumatoid arthritis, and that changes the profile of Abivax dramatically," he said.
Based on the trial data, Abivax will now accelerate its trialing of ABX464 in ulcerative colitis.
"We will now move it into a Phase IIb trial in approximately 180 patients with moderate to severe ulcerative colitis," the CEO said.
He added that the latest clinical data data could be extrapolated beyond that indication.
"You can define this as ulcerative colitis but also as inflammatory bowel disease and by inference Crohn's disease, and we will soon initiate a Phase IIa clinical trial in Crohn's with ABX464. But you can go more broadly and identify the potential as the whole anti-inflammatory space," he said, adding that "the global sales of these products are exceeding $30bn by now and that speaks to the potential of drugs in that space that are safe and efficacious."
Pharma Partner Sought
To be successful though, Abivax will need to find a big pharma to partner its lead ABX464.
"We are too small a biotech to market ABX464 in either of these important but competitive therapeutic indications, those being HIV or ulcerative colitis. We want to have a partner for the Phase III program where we would certainly seek a partial funding by a third party and the market expertise offered from a larger pharma company."
He said the ideal situation would be for Abivax to have just one partner.
"That said, I could also see the possibility of Abivax partnering with two companies involving either a global split of the rights to ABX464, or the rights being distributed by indication. We'd be open to that idea as well," Ehrlich said.
Regulatory Pathways
The regulatory pathway for the drug would differ depending on the indication, he noted.
"There is a wide gap in available guidance from the regulatory agencies regarding regulatory pathways for therapies to treat HIV and ulcerative colitis – in HIV there is very little definition so far, while in ulcerative colitis there is very clear guidance from the FDA and in Europe as to what is required if you want to eventually file your NDA in a successful way," the CEO explained.
"An advantage of the inflammatory indications is that many aspects of the process are set in stone, and it is up to us the company to bring the data being requested.
"On the HIV side, however, it's still more of a back-and-forth exercise with regulatory authorities in order to get the desired label for the product," Ehrlich said.