Upcoming events – Shire in Sanfilippo A while Sage looks to its lead asset


Welcome to your weekly digest of approaching regulatory and clinical readouts. Phase II data on Shire’s SHP610 for the enzyme deficiency disorder Sanfilippo A syndrome are due this spring, and will be instrumental in determining whether this asset attains its forecast best-selling position.

Meanwhile, results are expected in the second half of the year from SAGE-547 in a rare and severe seizure disorder. While this showed promise in an earlier trial the real test for phase III will be whether placebo overshadows treatment response.


Patients with Sanfilippo A syndrome are unable to produce heparan N-sulfatase, and like sufferers of all forms of mucopolysaccharidosis III experience progressive intellectual decline resulting in severe dementia and progressive motor disease. The disorder first becomes apparent in young children, and patients rarely live beyond their early twenties.

The disorder’s orphan nature means that Shire will be able to charge top dollar for SHP610 if it reaches the market. Analysts at Jefferies say that the drug could have peak sales potential of $500m or more.

The phase IIb HGT-SAN-093 trial has enrolled 18 patients aged between 12 and 48 months. SHP610, a formulation of the missing enzyme, was administered at two doses: 45mg either every two or every four weeks for 48 weeks via a surgically implanted intrathecal delivery device. A placebo group is also part of the trial; six patients will be randomly assigned to each group.

HGT-SAN-093’s primary endpoint is change in developmental quotient, assessed by neurocognitive testing. If it hits, and there are no safety signals, it will be that much closer to market.

It is easy to see that chronic intrathecal delivery via an implant will be no picnic for very small children. Even so, according to EvaluatePharma’s consensus forecasts, SHP610 could be the top product for Sanfilippo A in 2022, with sales of $277m. Shire’s emphasis on orphan conditions could continue to pay off if HGT-SAN-093 succeeds.


Sage Therapeutics’ phase III Status trial tests SAGE-547 as an adjunctive therapy for the treatment of super-refractory status epilepticus (SRSE), a persistent, unremitting seizure refractory to benzodiazepines and second-line anti-seizure drugs. Patients are typically placed into a medically induced coma. 

SAGE-547 is a GABA A receptor modulator and has been granted US fast-track and orphan drug designations. In the double-blind trial patients are randomised 1:1 to receive either SAGE-547 or placebo in addition to standard-of-care third-line anti-seizure agents for six days.

The primary outcome is  number of patients able to be weaned off third-line agents before the end of the SAGE-547 or placebo infusion and remain off all third-line agents for over 24 hours after the end of the SAGE-547 or placebo infusion.

In a Phase I/II open-label study of 22 evaluable patients, 73% were successfully weaned off anaesthetic agents and SAGE-547 within five days of starting treatment, and 82% within six days, without the need to reinstate anaesthetics in the following 24 hours.

Controversy arose last month when the hedge fund Kerrisdale Capital said SAGE-547 would fail to outperform placebo to a statistically significant degree in phase III, and called the project "little more than a Band-Aid" that leaves the underlying causes of SRSE untouched. The report also questioned the potential market size, and Sage shares fell 12.9%.

However, the sellside defended Sage, and shares have since recovered. SAGE-547, the company’s lead asset, is forecast to sell $996m by 2022, according to consensus from EvaluatePharma.

Another trial in postpartum depression is expected to read out in the second quarter, and could build on a previous study in four patients that reported a mean 24.7-point improvement in the Hamilton Rating Scale for Depression score, a secondary endpoint. However, there was no placebo group (Sage advice takes Marinus higher, June 10, 2015).

The upcoming results in SRSE will determine whether worries over placebo response are warranted.

Project Study Trial ID
SHP610 HGT-SAN-093 NCT02060526
SAGE-547 Status NCT02477618
SAGE-547 (postpartum depression) NCT02614547

To contact the writers of this story email Elizabeth Cairns or Joanne Fagg in London at news@epvantage.com or follow @EPVantage on Twitter

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