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ALS Drug Shown to Extend Patient Survival

Motorized wheelchair

(Kevin Phillips, Pixabay)

16 Oct. 2020. Results of a clinical trial show a drug to treat amyotrophic lateral sclerosis, or ALS, extends patients’ survival by several months and slows decline of their functions. Findings from the trial on patient survival, conducted by Massachusetts General Hospital in Boston and the drug’s developer Amylyx Pharmaceuticals Inc. in Cambridge, Massachusetts, appear in today’s issue of the journal Muscle & Nerve (paid subscription required).

ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder where neurons or nerve cells controlling muscles in the body begin to waste away, and can no longer send or receive signals from the brain or spinal cord. As the nerve cells stop functioning, muscles in the limbs, and later speech and breathing muscles, begin weakening and eventually stop functioning. Most people with the disease die of respiratory failure. According to Johns Hopkins University, ALS affects some 30,000 people in the U.S., with 6,000 new cases reported each year.

Amylyx Pharmaceuticals is developing AMX0035 that aims to slow the disease’s progression by targeting two sources of stress on nerve cells believed to contribute to cell death and inflammation associated with ALS. One stress source is the mitochondria or energy center of the cell, while the second source is the endoplasmic reticulum, a network of sacs and tubes that takes up much of the internal space of the cell, and transfers molecules between the nucleus and the rest of the cell. The company says both of these stress pathways need to be addressed to treat neurodegenerative diseases such as ALS.

AMX0035, says Amylyx, is made of two approved compounds that together work on both of the stress sources: phenylbutyrate for mitochondrial stress and tauroursodeoxycholic acid for endoplasmic reticulum.  Both compounds were tested individually with ALS patients earlier, but AMX0035 is designed to combine and optimize their effects.

The mid- and late-stage clinical trial enrolled 137 participants diagnosed with ALS symptoms in the previous 18 months, from an initial screening of 177 patients. Participants at the 25 sites in the U.S. were randomly assigned to receive AMX0035 or a placebo on a two-to-one basis for six months, administered once a day for three weeks, then twice a day for 21 weeks. The study team looked primarily for changes in participants’ scores on a standard 48-point rating scale of muscle activity and day-to-day functions among ALS patients.

As reported by Science & Enterprise in September, results show functional ratings for the 89 participants receiving AMX0035 declined at slower pace, 1.24 points per month, than the 1.66 points per month for the 48 participants receiving the placebo, a difference large enough for statistical reliability.

The new findings reported on an extension of the trial. After the initial six-month period, participants could choose to receive AMX0035 for another 35 months, with researchers tracking their health during that time. All but two of the original 137 participants chose this option.

Follow-ups by the study team show participants originally receiving AMX0035 lived for a median of 25 months, compared to 18.5 months for participants receiving the placebo, a difference of 6.5 months. About three-quarters of the participants (77%) were taking other approved drugs for ALS symptoms, during the initial trial period and the extension.

“In this trial,” says Mass. General neuroscientist and principal investigator Sabrina Paganoni in an Amylyx statement, “we have seen promising functional and survival benefits,” and adds, “We have many reasons to be encouraged today.”

“These results provide evidence to support the rapid advancement of AMX0035,” notes Josh Cohen, co-CEO and co-founder of Amylyx. “We will continue to work collaboratively and expeditiously with global regulatory agencies to bring this potential treatment to people living with ALS in accordance with the applicable regulatory approval processes.”

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