HHE 2018 | Page 134

deemed to be motor milestone responders compared with none of those in the sham procedure group

• At the end of the study , the proportion of responders assigned to nusinersen had increased to 51 % yet again none of those in the sham procedure became responders

• At the study end , all participants were given the opportunity to enter an open-label extension trial termed SHINE .

The results for the second primary end-point , assessed at the study end , are shown in Table 3 , illustrating a significantly prolonged event-free survival ( hazard ratio 0.53 , p < 0.05 ) in those given nusinersen .

CHERISH The results for the change in primary outcome at the study end ( 15 months ) are shown in Figure 1 . These data represent the proportion of patients who achieved a 3 or more-point increase in the HFMSE score ( that is , a clinically meaningful change ).

The data from CHERISH clearly show that children assigned to nusinersen achieved a clinically meaningful change in motor function compared to those given the sham procedure . To date no results have been made available for the NUTURE study .

The effect of nusinersen has also been explored in several other Phase II trials . 9

Adverse effects The most commonly reported adverse effects that occurred in at least 20 % of nusinersen treated patients and which were reported at least 5 %

Table 4

Adverse events recorded in the ENDEAR trial

Adverse effect Nusinersen (%) Control (%)

Constipation 30 22

figure 1

Proportion of HFMSE responders in the CHERISH study ( difference statistically significant , p = 0.0006 )

Nusinersen ( n = 84 )

Sham ( n = 42 )

0 10 20 30 40 50 60 HFMSE RESPONDERS %

more frequently than in controls during the ENDEAR trial , are shown in Table 4 .

Place in therapy Nusinersen represents an important advance in the management of patients with SMA being the only effective treatment for the disease and the drug has been approved by the FDA for the treatment of patients with subtypes 1 , 2 or 3 . In the UK , the drug is available through an expanded access programme but the National Institute for Health and Care Excellence has yet to decide upon the wider availability of the drug . However , the National Centre for Pharmacoeconomics has already decided that nusinersen is not cost-effective at the submitted price although the Scottish Medicines Consortium has accepted nusinersen for restricted use within NHS Scotland but only for patients with symptomatic type 1 SMA ( infantile onset ). 11

While the clinical evidence is convincing , what remains unclear is the extent to which the drug has a lasting effect on patients . Hopefully future trials will provide that much-needed evidence .