Vitamin B12 treatment Rozebalamin approved for ALS in Japan
Therapy aims to slow functional decline in ALS patients
An ultra-high dose of mecobalamin, a naturally occurring form of vitamin B12, has been approved in Japan under the brand name Rozebalamin to treat amyotrophic lateral sclerosis (ALS).
The therapy, which will be manufactured and marketed by Eisai, is intended to slow functional decline in people with the disease.
The September approval was based on data from a Phase 3 clinical trial called JETALS (NCT03548311), in which Rozebalamin significantly slowed ALS disease progression when given alone or in combination with standard ALS treatments.
“Eisai is committed to further addressing the diverse needs of, and increasing the benefits of, patients and their families by providing Rozebalamin as a new treatment option for ALS patients,” the company said in a press release.
Mecobalamin is highly sensitive to light, which can cause it to become chemically unstable. The company created a vial that offers a high level of light protection, with a resealable window on the neck that allows healthcare providers to easily see the medication during dilution and withdrawal. The Japan Institute of Design Promotion gave the packaging its Good Design Award, according to a separate company press release.
Slowing disease progression
ALS is a neurological disease characterized by the progressive loss of motor neurons, the nerve cells that control voluntary movement. As the brain becomes less able to control muscle movements, patients experience worsening muscle weakness and other symptoms such as difficulty breathing, speaking, and swallowing.
A few therapies are approved to treat ALS, but their ability to slow disease progression and extend survival is limited.
Vitamin B12, found in foods including meat, fish, and dairy, has many key functions in the body, including supporting nerve cell health and function. A small clinical trial in ALS patients found that the Rozebalamin formulation consistently improved brain-muscle communication when given at very high doses (25 mg).
A later Phase 2/3 trial (NCT00444613) in Japan investigated one of two doses of Rozebalamin (25 mg or 50 mg) against a placebo, given twice weekly for 3.5 years. While the trial failed to demonstrate a significant slowing in disease progression with either dose, the findings suggested that a subgroup of patients with early ALS and moderate disease progression could potentially benefit from the higher dose.
JETALS was then launched to confirm the benefits in this subgroup. It enrolled 130 adults with early ALS who had received an ALS diagnosis up to one year before entering the trial and who were progressing moderately. This was defined as a 1-point to 2-point decline in the Revised ALS Functional Rating Scale (ALSFRS-R) total score over an initial three-month observational period.
Participants were randomly assigned to receive a 50 mg dose of Rozebalamin or a placebo, administered via twice-weekly injections into the muscles, for 16 weeks. The main goal was to determine whether the ultra-high dose Rozebalamin could significantly slow disease progression on the ALSFRS-R after 16 weeks, or about four months.
Data confirmed the findings from the previous trial. After 16 weeks, patients on Rozebalamin had experienced a 43% lower decline in ALSFRS-R scores, indicating a significant slowing in disease progression, compared with a placebo.
Approximately 90% of participants in both groups also taking riluzole, as approved ALS therapy sold as Rilutek, Tiglutik, and Exservan. In these patients, Rozebalamin was linked with a 45% slower progression.
There was also a significant decrease in the blood levels of homocysteine, a molecule that causes damage to motor neurons and other cells in the brain and spinal cord, in treated ALS patients.
Rozebalamin was generally well tolerated, with about 7.7% of patients experiencing side effects. The most common adverse reactions included constipation, pain at the injection site, fever, irregular heart rhythms, and rash.
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