PTC, partner Roche to kick-start PhII SMA study; SMA Type 1 test on the horizon

New study set to trigger a $20 million payment from Roche to PTC

As Roche ($RHHBY) continues to try to hit all the bases in this rare disease, its partner PTC Therapeutics ($PTCT) has started a midstage study for its candidate against certain forms of spinal muscular atrophy (SMA).

The Phase II Sunfish study will specifically look at both younger and adult Type 2/3 SMA patients using RG7916, a med that has the backing of Roche.

The test will be split into two parts: The first part will look at safety and tolerability through escalating doses of RG7916. After dose selection, the study will move on into a pivotal second part homing in on the efficacy of the med.

In terms of timelines, the second part of the study “is expected to begin in 2017,” according to the biotech, and will also pull the trigger on a $20 million milestone payment to PTC from Roche.

SMA, which can affect up to 10,000 children around the world, comes under four main types: Types 1, 2 and 3 appear in childhood; Type 4, also known as adult-onset SMA, appears in adulthood.

SMA Type 1 occurs when a protein, known as SMN, is not produced sufficiently because the SMN1 gene is missing. Without this protein, the motor neurons die as do other key tissues, such as muscle.

This type, which is being targeted by Fierce 15 company AveXis (which is also backed by Roche), is seen as the most severe as around 90% of children born with this form never see their second birthday, and in their short lives will never sit, crawl or walk.

PTC said it was also seeking to start an early trial in SMA Type 1 “in the coming months,” in a two-part study named Firefish looking at safety and efficacy.

Symptoms of SMA Type 2, also known as intermediate SMA or chronic infantile SMA, include muscle weakness and floppiness that usually appear between 7 and 18 months of age. In SMA Type 3, sometimes called Kugelberg-Welander disease, symptoms of muscle weakness and floppiness appear after 18 months of age, but the actual age of onset is very variable and symptoms may not appear until late childhood or early adulthood.

Each child with SMA Type 3 is different, but the onset of muscle weakness is gradual and children are generally able to walk until late childhood and sometimes into adolescence.

RG7916 is an oral small molecule survival motor neuron 2 (SMN2) splicing modifier. It works by directly targeting the underlying molecular deficiency of SMA by modulating SMN2 splicing to increase expression of stable full-length SMN2 mRNA from the SMN2 gene.

“We are excited to initiate clinical studies in SMA patients with RG7916 and advance our Spinal Muscular Atrophy program forward,” said Stuart Peltz, CEO of PTC Therapeutics.

“An oral small molecule splicing modifier has the potential benefit of systemic exposure to promote SMN protein in all affected organs and tissues. This attribute, along with an ease of administration, provides promise for this program to have a meaningful benefit for SMA patients.”

AveXis’ ($AVXS) FDA breakthrough med AVXS-101, which last month posted some encouraging SMA Type 1 data from a small Phase I test, is designed to address the monogenetic root cause of SMA and prevent further muscle degeneration by addressing the defect in and/or loss of the primary SMN gene.

Another contender in the fight to market is nusinersen, developed by Biogen ($BIIB) and Ionis ($IONS), which also posted positive data last month. In the Phase III Endear study, their med showed statistically and clinically significant improvement in the primary endpoint, which included greater movement in kicking, walking, crawling and sitting, than worsened. They are also looking to cover a number of SMA types.

Nusinersen works as an antisense oligonucleotide that is designed to alter the splicing of SMN2, a gene that is nearly identical to SMN1, in order to increase production of fully functional SMN protein.