David Guy, parent of Kaila who was diagnosed with acid sphingomyelinase deficiency (ASMD), recounts his initial shock when he was told of Kaila’s rare disease. David and his wife were devastated. They had no idea what this would mean or what Kaila’s future would be like. Even treatment options seemed elusive. David now feels extremely fortunate that Kaila was accepted into olipudase alfa clinical trials.
Globe Newswire’s 31 August 2022 press release heralds the FDA’s approval of XenopozymeTM as the first disease-specific ASMD treatment for adult and pediatric patients. ASMD is a progressive genetic disorder with high mortality. There are less than 120 known cases in the United States. Two-thirds of these patients are children.
The Path Forward for ASMD
Breakthrough Therapy designation was awarded to Xenpozyme by the USFDA. The designation is given on behalf of drugs that are being developed to treat severe or life-threatening disorders.
The next step was the evaluation of Xenpozyme by the FDA under a designation called ‘Priority Review.’ This procedure evaluates medicine having the potential to significantly improve the safety or efficacy in the treatment of severe conditions.
Japanese and European Approvals
Japan approved Xenpozyme in March of 2022 followed by the EC in June of 2022. Japan’s designation called ‘Sakigake’ (pioneer) marked a first in the entire world for olipudase alfa.
Signs and Symptoms
There is no specific age group that can be used to suggest the onset of ASMD. The disorder can present in infancy, childhood, or in adulthood. Signs of the disease may involve, among other symptoms, an enlarged liver or spleen, lung infections, breathing difficulties, and often excessive bleeding or bruising.
Thus far, management of the disease has been limited to supportive care. This involved simply addressing individual symptoms and monitoring the patient’s condition.
The ASCEND CLINICAL TRIALS
The ASCEND and the ASCEND-Ped trials formed the basis for the FDA’s approval of Xenpozyme. The drug showed improvement in adult and children’s lung function and platelet count, as well as liver and spleen volume reduction. Xenpozyme also demonstrated a satisfactory safety profile.
ASMD can be referred to as ASMD A and ASMD B while ASMD A/B is considered intermediate and includes central nervous system involvement to varying degrees.
Thirty-one patients with ASMD A/B or type B randomly received Xenpozyme or placebo for a total of fifty-two weeks. The drug is administered intravenously at two-week intervals. Dose escalation is required and is followed by a maintenance phase.
The safety and efficacy of Xenpozyme were evaluated during the ASCEND trial. The complete Globe NewsWire article including detailed clinical trial results is available here.
The most common adverse reactions to the drug reported by adults were cough, headache, diarrhea, ocular hyperemia, and hypotension.
The ASCEND-Peds trial involved eight pediatric patients under the age of twelve who had ASMD A/B or B type. Type ASMD-A was not included in the trial.
Xenpozyme was administered to the pediatric group of patients to evaluate the tolerability and safety of the drug.
The group of eight pediatric patients fulfilled study requirements and went on to participate in an extension trial that also explored liver and spleen enlargement, platelet count, and progressive lung disease.
Adverse Events
Severe adverse reactions were reported within twenty-four hours after infusion at a higher rate in the ASCEND–Ped trial than in the adult ASCEND trial. These symptoms included anaphylaxis (allergic reaction), hypersensitivity, and reactions deemed to be infusion related.
Reactions most commonly reported in the pediatric group (greater than twenty percent) were found to be cough, abdominal pain, pyresia (characterized by a rise in core temperature), diarrhea, vomiting or nausea, fatigue, headache, urticaria (rash or swelling), arthralgia (painful joints), pruritus (itchy skin), and pharyngitis (sore throat).
Xenpozyme should be available in the United States within several weeks.
