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IONS: SMA Competitors Have A Long Way To Go
Ionis Pharmaceuticals, Inc.
Biotechnology

Jim Birchenough, MD, Senior Analyst [phone] [e-mail]
Chuck Whitesell, Associate Analyst [phone] [e-mail]
Nick Abbott, Associate Analyst [phone] [e-mail]
Yanan Zhu, Associate Analyst [phone] [e-mail]
Wells Fargo Securities, LLC.
We are reiterating our OUTPERFORM rating on shares of Ionis Pharmaceuticals (IONS) following review of competitive data in Spinal Muscular Atrophy (SMA) from both an oral splice modulator from PTC Therapeutics (PTCT) and an alternate spherical nucleic acid format of SPINRAZA from Exicure (XCUR). While clinical data from PTCT appear promising we believe that cross trial comparisons are difficult with potential differences in baseline characteristics and see timelines to approval extending several years with some risk to safety data based on experience with other splice modulators.
Pre-clinical data for Exicure (XCUR) is even further removed as a potential commercial challenge to SPINRAZA, in our opinion, as we would want to see clinical safety data before assessing relative therapeutic index differences with SPINRAZA.
PTC Therapeutics (PTCT), a competitor for Ionis Pharmaceuticals (IONS) and partner Biogen (BIIB) in SMA, reported data from the FIREFISH study of its oral SMN2 RNA splicing modulator, risdiplam (RG7916), partnered with Roche, in babies with Type 1 SMA over the weekend at the Cure SMA meeting.
FIREFISH is a two-part pivotal study in infants with SMA. Data reported at the meeting were from Part 1 of the study, which is a dose escalation study (planned enrollment of 21 infants). Part 2 of study is a single-arm open label study currently ongoing, with planned enrollment of 40 infants.
In Part 1 of FIREFISH, the median increases in CHOP-INTEND were 5.5 points (n=20) at day 56, 12.5 points (n=16) at day 119, and 14 points (n=11) at day 182. The proportion of patients achieving greater than 4-point increase from baseline in CHOP-INTEND was 75% at day 56, 94% at day 119, and 91% at day 182. No babies required a tracheostomy or permanent ventilation since study initiation and no baby lost the ability to swallow. The principal investigator of the study also presented video footage demonstrating the ability of study participants to control their head, roll or sit. The median age at first dose was 6.7 months (mostly after 5 months). The oldest patient on trial is currently 23.8 months of age. Risdiplam is described as well tolerated, with no study withdrawal due to AEs.
Recall that in SPINRAZA?s phase 3 ENDEAR study in infants with SMA, 71% of patients in the SPINRAZA group achieved greater than 4 point increase from baseline in CHOP-INTEND vs. 3% in the control group at the end-of-trial visit (6, 10 or 13 months).
Also at the Cure SMA meeting,

Exicure (XCUR) presented preclinical data demonstrating that SPINRAZA in the company?s spherical nucleic acid (SNA) format prolonged survival by 4-fold compared with SPINRAZA in the delta-7 SMA mouse model, and also mitigated toxicity of SPINRAZA at the highest dose tested.



Ionis Pharmaceuticals, Inc. (IONS-NASDAQ) --OUTPERFORM (1)

Price as of 6/18/2018: $43.1
FY 18 EPS: $0.48
FY 19 EPS: $2.61
Shares Out.: 125.3 MM
Market Cap.: $5,441.78 MM

Sector Rating: Biotechnology, Overweight


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