ALNY: 2023 guidance in-line with our expectations
BAML / Feb 24

Alnylam (ALNY, Buy, $262 PO) reported 4Q product revenue of $262mn which was
pre-announced at a competitor’s conference early this year. For 2023, the company
provided net product revenue guidance range of $1.2-$1.285bn (BofA: $1.237bn;
Consensus: $1.324bn). On the call, management noted Amvuttra launch remains strong
with average monthly new patient start forms of 60 vs. 30 for Onpattro prior to
Amvuttra launch. This suggests the broadening of patient base with roughly 53% of start
forms coming from new patients. We think Amvuttra will exceed Onpattro in
transthyretin amyloidosis related polyneuropathy (ATTR-PN) sales by 2024. The company
launched Amvuttra in Germany and Japan in 4Q and is looking to launch in the UK in
1Q23. On patisiran in transthyretin amyloidosis related cardiomyopathy (ATTR-CM),
management noted that they do not have any additional information on the topics that
the FDA wants to explore in the advisory committee (ad com). Recall, patisiran received
prescription drug user fee act (PDUFA) action date of October 8th for potential approval
in ATTR-CM and the agency plans to hold an ad com (which was in-line with our
expectations). On the call, the company announced that they are not looking to seek
approval of patisiran in ATTR-CM in the ex-US markets (except Brazil), largely because of
faster enrollment of HELIOS-B which is expected to readout in early 2024. We agree
with the company’s decision as with priority review, vutrisiran could likely be approved in
ATTR-CM by early 2025.

Additional takeaways from the earnings call include: 1) announced topline data from the
biannual dosing regimen trial of vutrisiran. While the 50mg biannual dosing vutrisiran
showed non-inferiority to 25mg quarterly vutrisiran, the company observed some TTR
recovery at the tail end of biannual dosing. As such, the company decided not to proceed
with the filing of biannual dosing vutrisiran, but rather focus efforts on its annual dosing
asset, ALN-TTRsc04, which started dosing patients in a phase 1 trial with expected
readout later this year. We note that ALN-TTRsc04 is fully owned by Alnylam and
therefore, there are no royalties to Sanofi tied to this asset, 2) remains on-track to
report topline data from ALN-APP in early 2023. Topline readout will include safety,
tolerability, target engagement and target knockdown data (by measuring soluble APP
alpha and APP-beta). Management noted that based on genetic data, 50% knockdown of
APP might be therapeutic, and believe that the drug will likely have a quarterly or
biannual dosing profile, 3) on-track to report KARDIA-1 data in mid-23 and KARDIA-2
at/around year end.

In our DCF-based model, we update for 4Q results. We remove ex-US sales for patisiran
in ATTR-CM and, also lower our US peak penetration to 3% (prev 5%), to reflect
management’s commentary and our recent physicians feedback suggesting uptake might
be limited due to the lack of cardiovascular outcomes data and given vutrisiran launch
will likely be only 12-18 months behind patisiran. We now estimate patisiran’s peak sales
in ATTR-CM of $218mn (prev $625mn). We also adjust our op ex to be in-line with
guidance. We reiterate our Buy with a new $262 PO (prev $267).