Over the weekend, Alnylam announced expanded data from the
phase II study of ALN-TTR02 (aka PATISIRAN) in the FAP form of TTR amyloidosis
at the ISFAP meeting being held in Brazil.
The data confirm the consistent knockdown potency of ALN-TTR02 and, most
interestingly, suggest that a new dosing regimen can address the most
rate-limiting safety issue encountered so far.
Compared to the 19-patient dataset revealed at the
Peripheral Nerve Society meeting at the end of June, the latest update includes
data from 9 more FAP patients that received the highest dose (0.3mg/kg) in the
once-every-3-week treatment regimen.
Previously only 3 patients received such dosing whereas the data from
the 6 patients with the once-every-4-week dosing indicated an undesirable TTR
rebound effect towards the end of the 28-day treatment cycle.
Data from the 12-patient once-every-3-week cohort now show that a
~80% persistent knockdown of TTR can be achieved although there still seemed to
be a minor rebound effect at the end of the 21-day treatment cycle (down to ~75% knockdown). It therefore needs to be watched whether the
apparent rebound effect worsens or maybe gets better with dosing for more than
the two infusions as performed in this study (open-label extension study ongoing).
The most exciting revelation, however, from the new data was
that there were no apparent infusion reactions in the 9 additional subjects. Previously, 3 out of 7 in the
once-every-4-week cohort of 0.3mg/kg experienced such reactions. Infusion reactions thus far tends to rank as
the rate-limiting safety issue in the development of SNALP-related RNAi
Therapeutics and although they appear to be readily managed by slowing the rate
of infusion, are dose-related, and generally occur only during the first infusion, it would put
everybody at ease if there were no such risk.
Rather than being the result of a streak of luck, the absence of
infusion reactions coincided with the institution of a 70-minute microdosing
strategy which Alnylam labeled as ‘proprietary’. If it holds up, it would definitely be good
news for Alnylam and FAP patients. Beyond
that, Tekmira may actually be the major beneficiary of such progress as its
pipeline rests on i.v.-administered SNALP RNAi Therapeutics such as ALN-TTR02.
By initiating a phase III study of Patirisan and further announcing fast-track designation for this product candidate, the company remains on track for an approval in 2016/7. Data from the competing RNaseH antisense compound by ISIS and GSK at the same meeting remains to be publicized.
By initiating a phase III study of Patirisan and further announcing fast-track designation for this product candidate, the company remains on track for an approval in 2016/7. Data from the competing RNaseH antisense compound by ISIS and GSK at the same meeting remains to be publicized.
