FDA Grants Orphan Drug Status to TQS-168 for ALS Treatment

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The U.S. Food and Drug Administration has granted orphan drug designation to Tranquis Therapeutics‘ experimental therapy TQS-168 for treating amyotrophic lateral sclerosis (ALS).

Orphan drug status is given to experimental therapies with promise for treating rare diseases — those affecting fewer than 200,000 people in the U.S. — for which no effective therapies are available.

The designation is accompanied by several incentives to help accelerate a treatment’s development including tax credits for qualified clinical trials, exemptions from certain fees, and seven years of market exclusivity if the medication receives regulatory approval.

“The orphan drug designation is an important regulatory milestone for Tranquis, further validating our efforts to develop TQS-168 … as a novel therapeutic option for people living with ALS,”  Jonas Hannestad, MD, PhD, chief medical officer at Tranquis, said in a press release.

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Inflammation is thought to play a critical role in ALS’s development. During a normal inflammatory response, myeloid cells – immune cells in the blood such as monocytes – travel to the site of a threat or injury where they launch an immune attack. But in ALS and other neurodegenerative conditions, these cells sometimes become overactive and release inflammatory molecules that damage nerve cells.

TQS-168 is a small molecule designed to modulate a protein called PGC-1a that’s on myeloid cells and regulates their energy metabolism. TQS-168 is thought to normalize energy metabolism, reprogramming the dysfunctional myeloid cells and lowering their activation.

TQS-168, delivered three times weekly, led to significant declines in levels of inflammatory monocytes and pro-inflammatory signaling molecules in a mouse model of ALS. Mice treated with the therapy also lived six days longer than untreated mice.

When blood samples from ALS patients were mixed with TQS-168, inflammatory monocyte levels – which are typically elevated in ALS patients – were reduced.

Encouraged by the data, Tranquis launched a Phase 1 trial (ISRCTN46651459) last year to evaluate the safety, tolerability, and pharmacokinetics of TQS-168 in 78 healthy volunteers in the U.K. Pharmacokinetics refers to a therapy’s movement into, through, and out of the body.

The trial consisted of a single-ascending dose part, wherein participants were randomized to receive a single oral dose of TQS-168 or a placebo, and a multiple-ascending dose part in which participants were treated with TQS-168 or placebo once or twice daily for a week. In both parts, participants were monitored during a two-week follow-up after treatment.

The company reported earlier this month that the trial had finished, and that single and multiple oral doses of TQS-168 were well tolerated and that there were no serious side effects. Side effects were mild, temporary, and did not lead to treatment being discontinued.

The therapy also showed a promising pharmacokinetic profile, reaching blood levels associated with therapeutic benefit in preclinical models.

Tranquis now expects to begin a Phase 2 study of the therapy in ALS patients by the end of the year.

“Earlier this month, we reported Phase 1 data on TQS-168 in 78 healthy volunteers demonstrating excellent pharmacokinetic properties and blood plasma exposures associated with clinical benefit in preclinical models, along with a favorable safety and tolerability profile,” Hannestad said. “We look forward to rapidly advancing our Phase 2 program in ALS.”

Exploratory development of TQS-168 for other conditions including frontotemporal dementia, Huntington’s disease, muscular dystrophy, and Friedreich’s ataxia is ongoing.