A phase 3 trial of Teva and Active Biotech’s laquinimod in relapsing-remitting multiple sclerosis (RRMS) missed its primary endpoint. The data represent another setback to the aryl hydrocarbon receptor activator, which has seen its reputation as a $4 billion (€3.6 billion) a year heir to Copaxone wiped out by a series of failures.
Teva enrolled 2199 patients in the phase 3 trial and randomized them to receive one of two doses of laquinimod or a placebo. Treatment in the higher dose arm was stopped last year. And Teva has now learnt the lower dose failed to outperform placebo in terms of time to confirmed disease progression, the primary endpoint. Bright spots in the data were confined to secondary endpoints. Laquinimod beat placebo in terms of change in brain volume and time to first relapse.
The subpar efficacy data come 15 months after cardiovascular side effects forced Teva to halt the use of the highest dose of laquinimod in the trial. That setback stirred up memories of the fate of roquinimex, the compound from which laquinimod was derived. A phase 3 trial of roquinimex was stopped one month after enrollment ended after serious cardiopulmonary toxicities were seen.
Dropping the higher dose appears to have resolved the safety concern. The only adverse events to affect more than 5% of patients in the lower-dose arm were headache, nasopharyngitis, back pain and arthralgia. And, when paired to the data on secondary endpoints, that has persuaded Teva to keep pushing ahead with ongoing trials of laquinimod in primary progressive MS and Huntington's disease despite the mounting evidence of it its ineffectiveness.
“Although we are disappointed by not meeting the primary endpoint, we did see positive results on a number of secondary and exploratory endpoints which fuels our belief in the potential of laquinimod as a possible treatment for neurodegenerative diseases. While we have no current plans to further pursue laquinimod in RRMS, we are continuing to study it in two other trials,” Teva CSO Michael Hayden, M.D., Ph.D. said in a statement.
The data dealt another blow to Active Biotech. Shares in the Swedish biotech traded down 66% following news of the failure, adding to the losses suffered by the company since its value peaked around the start of 2011. Later that year, Active Biotech and Teva posted weak clinical trial data on laquinimod. The first data drop raised doubts about whether laquinimod would be as big a drug as the partners hoped. The second data drop raised doubts about whether laquinimod would be a commercial drug at all.
Those readouts marked the start of a losing streak for Active Biotech. In 2013, a phase 2/3 trial of the company’s tumor-targeting superantigen Anyara in patients with renal cell cancer missed its primary endpoint. And in 2015 Ipsen discontinued development of the immunotherapy tasquinimod in prostate cancer after it failed to improve overall survival.
The upshot of these failures is Active Biotech’s pipeline consists mainly of battle-scarred assets. A deal with NeoTx for Anyara means that asset is classed as being in active development. And the continued willingness of Teva to invest in laquinimod means that program is still stumbling down the pipeline. Beyond that, Active Biotech has been trying to offload paquinimod, tasquinimod and SILC without success.
Shares in Active Biotech have fallen 97% since the start of 2011.