Date: 2018-04-24
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 2018 Annual Meeting of the American Academy of Neurology (AAN) Annual Meeting in Los Angeles
Company: Avexis (USA - TX)
Product: AVXS-101
Action
mechanism:
Disease: spinal muscular atrophy (SMA) Type 1
Therapeutic area: Rare diseases - Genetic diseases - Neuromuscular diseases
Country: USA
Trial details:
Latest
news:
Treatment Durability and Motor Milestone Achievement from Long-Term Follow-Up Study:
*At baseline, none of the patients in Cohort 2 had achieved any of the listed motor milestones except for bringing a hand to the mouth. As of December 15, 2017, the majority of these patients had reached at least one major motor milestone. No patients in Cohort 1 are listed, since none attained any motor milestones. NA denotes not available, and NIV denotes noninvasive ventilation. Plus signs indicate achievement of milestone.
a. Event-free survival (the primary efficacy outcome) was defined as the age at the end of the trial at which patients were free of ventilatory support, which was defined as the need for ventilation for at least 16 hours per day for at least 14 consecutive days in the absence of acute reversible illness or perioperatively.
b. According to item 20 on the Bayley Scales of Infant and Toddler Development, rolling over is defined as movement of at least 180 degrees both left and right from a position of lying on the back.
c. Sitting unassisted for at least 5 seconds is in accordance with the criteria of item 22 on the Bayley Scales of Infant and Toddler Development gross motor subtest and surpasses the 3-second count that is used as a basis for sitting (test item 1) on the Hammersmith Functional Motor Scale–Expanded for SMA. Sitting unassisted for at least 10 seconds is in accordance with the criteria used in the World Health Organization Multicentre Growth Reference Study. Sitting unassisted for at least 30 seconds defines functional independent sitting and is in accordance with the criteria of item 26 on the Bayley Scales of Infant and Toddler Development gross motor subtest.
d. Nutritional support refers to the placement of either a gastrostomy tube or a nasogastric tube, as determined by the preference of the parents or the primary physician. Once enrolled in the trial, all the patients who required nutritional support underwent gastrostomy-tube placement, and none were removed during the trial.
e. Data are from Finkel et al.
f. Defined as nasogastric tube or gastrostomy tube. Data are from Finkel et al.
** Data are from De Sanctis et al.
O Denotes milestone achieved during LTFU.
Nutritional and Respiratory Support
Patients in Cohort 2 showed a reduced need for nutritional and ventilatory support and improvement in swallowing function. According to natural history, nearly all patients with SMA Type 1 require nutritional and respiratory support by 12 months of age, and most patients are not able to swallow or speak effectively.
Cohort 2
Age at Gene Transfer (mos)
Event-Free Survivala
Event-free Survival and Motor and Other Milestones Among the 12 Patients in Cohort 2 as of December 15, 2017*
Brings Hand to Mouth
Controls Head
Rolls Overb
Sits with Assistance
Sits Unassistedc
Other Achievements
?5 seconds
?10 seconds
?30 seconds
Speaks
Swallows
No NIV Use
No Nutritional Supportd
E.04
5.6
31.1
+
+
+
+
+
O
O
+
+
E.05
4.2
28.5
+
+
+
+
+
+
+
+
+
+
+
E.06
1.9
26.1
+
+
+
+
+
+
+
+
+
+
+
E.07
3.6
28.1
+
+
+
+
+
+
O
+
+
+
E.08
7.9
32.4
+
E.09
4.9
28.9
+
+
+
+
+
+
+
+
+
+
+
E.10
0.9
25.3
+
+
+
+
+
+
+
+
+
+
+
E.11
2.3
27.7
+
+
+
+
+
+
+
+
+
E.12
2.6
26.8
+
+
+
+
+
+
+
+
+
+
+
E.13
0.9
25.4
+
+
+
+
+
+
+
+
E.14
4.1
27.9
+
+
+
+
+
+
+
+
+
+
+
E.15
2.1
26.3
+
+
+
+
+
+
+
+
Patient with Outcome (%)
This Trial
100
%
100
%
92
%
75
%
92
%
92
%
92
%
92
%
92
%
92
%
58
%
50
%
Natural History
8% by 20 monthse
NA
0
0**
0**
0**
0**
0**
NA
NA
NA
25% by 13 monthsf
“The long-term follow-up data from the Phase 1 trial showed unprecedented event-free survival, continued developmental milestone achievement and long-term durability, with no new safety findings,” said Dr. Sukumar Nagendran, Chief Medical Officer of AveXis. “In aggregate, these data presented at AAN demonstrate a one-time administration of AVXS-101 appears to have a potentially clinically transformative and durable impact on patients with SMA Type 1.”
With regard to the ongoing Phase 1 trial of AVXS-101, the FDA stated the following in the meeting minutes: “We strongly recommend that at the completion of the study, you request an end-of-Phase 1 meeting to evaluate the adequacy of data to support future product development, including a discussion of whether the data from the Phase 1 study might provide the substantial evidence necessary to support a marketing application.”
The company’s strategy with the SMA Type 1 program is to complete the ongoing Phase 1 trial and, in parallel, execute on the single-arm pivotal trial, while continuing collaborative discussions with the FDA regarding the most expeditious pathways for FDA approval of AVXS-101.
