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patients could take risdiplam on their own, and not have to go to a doctor’s office. Some SMA patients have scoliosis or spinal fusions and may not be eligible for therapy infused into the spine; some might have trouble tolerating the painful spinal taps three times a year. “This is another advantage of an oral medicine,” Begelman says.
Roche isn’t just testing risdiplam in infants, but in teenagers and adults as well. The data backing Spinraza and Zolgensma has come from younger patients.
It’s hard to compare results across trials, but until there are head-to-head studies, Spinraza and Zolgensma have set a high bar for safety and efficacy. And Roche still has a ways to go. This week’s AAN data are only from dose-finding studies, which aren’t designed to show whether the drug can change the disease. That work is now underway, with data expected later this year and in early 2020.
Here are the results from the Roche studies FIREFISH and SUNFISH.
FIREFISH: This is a study in babies one to seven months old with Type 1 SMA. Roche said, a median of 14.8 months after beginning treatment, seven of the 17 babies who got the risdiplam dose being carried forward could sit independently for at least five seconds—the main goal of the “confirmatory” portion of the trial. Additionally, 11 could sit with or without support; nine had head control; and one could stand.
Fifteen of the 17 getting the key risdiplam dose are alive. Their CHOP-INTEND scores have improved. And none have lost the ability to swallow or needed a ventilator or a tube inserted into their windpipe to help them breathe.
“It’s really encouraging how much improvement we’ve noticed in these children,” says Giovanni Baranello, a Pediatric Neurologist at the Carlo Besta Neurological Institute in Milan, Italy, and the lead investigator of the FIREFISH study.
Despite side effects including fever, respiratory tract infections, vomiting, diarrhea, and pneumonia, no patient stopped treatment, Begelman says.
SUNFISH: This study tests risdiplam in patients from two to 25 years old and have either Type 2 or 3 SMA. Some might be unable to sit, while others can walk. To judge their progress, Roche is using a neuromuscular disease test called Motor Function Measure-32.
In the dose-finding portion of its study, Roche found that 25 of 43 patients (58 percent) evaluated for at least 12 months saw their MFM-32 scores rise at least three points. (In a disease where function steadily decreases, any increase in functional score is notable.)
The benefits were less pronounced for older patients, 12 to 25 years old, which appears to jive with what’s become known about SMA; the earlier the treatment, the better the benefit. “We’ll learn as we collect more data,” Begelman says.
So will patients. Roche enrolled 180 of them in the confirmatory part of the study. Baranello is keeping an eye on what patients say about their experience—particularly the teenagers and young adults. “Ultimately they are the ones responsible for making the decision to be treated,” he says.
Here are a few more notes from the meeting:
—The latest class of FDA-approved migraine therapies are injectable drugs that block a protein called calcitonin gene-related peptide (CGRP). AAN offered a peek at experimental CGRP drugs in pill form vying to be a more convenient alternative. Allergan (NYSE: AGN) presented data for two CGRP pills, atogepant for migraine prevention and ubrogepant for acute migraine pain. In a research note, RBC Capital Markets analyst Brian Abrahams said both look viable, with no major signs of liver problems so far. But he added that atogepant’s efficacy “looks modestly less robust” than the injectable CGRP drugs, flattening out after the second month of treatment.
—Evercore ISI analyst Umer Raffat saw a possible red flag in ubrogepant. In a research note, Raffat said Allergan disclosed rhabdomyolysis—the death of muscle tissue and the release of muscle fiber into the blood—in a small number of patients. Neither Teva Pharmaceutical (NYSE: TEVA) nor Amgen (NASDAQ: AMGN) reported the side effect in their injectable drugs, which are now on the market. Alder BioPharmaceuticals (NASDAQ: ALDR) reported one case for its experimental infusion eptinezumab, which is lagging behind its rivals. Raffat added that he spotted one muscle injury case in the data for the Biohaven (NASDAQ: BHVN) CGRP pill rimegepant.
—An injectable drug for the inherited neurodegenerative disorder Huntington’s disease proved enough in a small study for the developers, Roche and Ionis Pharmaceuticals (NASDAQ: IONS) to move into a large Phase 3 trial. The Phase 1/2 study, comprising 46 patients, was published in the New England Journal of Medicine. It showed that the drug, IONIS-HTTrx, lowered the amount of mutant huntingtin protein in patients’ cerebrospinal fluid, which seems to indicate that the drug is blocking production of the protein. The study did not last long enough to measure a therapeutic effect. There is no cure for Huntington’s, and current treatments do not slow the progression of the disease.
—There was mixed news in the field of amyotrophic lateral sclerosis (ALS), sometimes known as Lou Gehrig’s disease. Cytokinetics (NASDAQ: CTYK) said its drug reldesemtiv failed to improve patients’ lung function in a 485-patient Phase 2 trial, FORTITUDE-ALS. But Cytokinetics will press ahead with a larger Phase 3 study because it saw positive signs outside the trial design. Cytokinetics shares were volatile but finished up 7 percent Monday. Development partner Astellas Pharma has not said if it would join Cytokinetics in the next phase, according to a Stat report.
—Another ALS treatment is moving into Phase 3. Biogen and its partner Ionis said that their ALS drug tofersen fared well in a 70-patient early stage trial and is moving into Phase 3, although analyst Abrahams of RBC said he wanted to see more evidence, including data showing improvements in patient function were correlated to an increase in the dose of tofersen. Tofersen is designed to treat a subset of ALS patients whose disease stems from the genetic variant known as SOD-1.