An Open-Label Long-term Follow-up Study to Evaluate the Effects of Sotatercept When Added to Background Pulmonary Arterial Hypertension (PAH) Therapy for the Treatment of PAH

This Phase 3 study is being conducted to assess the long-term safety,
tolerability, and efficacy of sotatercept in PAH. Long-term follow-up of
patients receiving sotatercept is important to understand the maintenance and
durability of treatment effect (especially in the presence of background PAH
therapy) and to provide greater opportunity for pharmacovigilance following
sotatercept treatment in the selected patient populations.

This LTFU study is supported by data from the PULSAR study (Phase 2,
NCT03496207), in which treatment with sotatercept resulted in hemodynamic and
functional improvements in the study participants, including those receiving
maximal PAH therapy with double/triple drug combinations and intravenous
prostacyclin.

Primary:
The primary objective of this open-label, LTFU study is to evaluate the
long-term safety and tolerability of sotatercept when added to background PAH
therapy in adult participants with PAH.

Secondary:
The secondary objective is to follow participants from parent sotatercept
studies that were treated with sotatercept or placebo and assess continued
efficacy

This open-label, LTFU study will evaluate the safety, tolerability, and
efficacy of sotatercept in participants with PAH previously treated with
sotatercept or placebo.

Consenting participants who meet the eligibility criteria can roll over to
A011-12 study to receive/continue receiving sotatercept plus
background PAH therapy. Administration of sotatercept will be via subcutaneous
(SC) injection(s) every 21 days.

Participants rolling over to the A011-12 study from a blinded parent study will
begin sotatercept treatment at a dose of 0.3 mg/kg (SC).
The dose for participants with stable hemoglobin (Hgb) and platelet counts
should be titrated up to 0.7 mg/kg at Visit 2 (Study Day 22 ± 3 days). However,
if at Visit 2 Hgb increases by more than 2.0 g/dL from baseline (Visit 1) and
this value is above the gender specific- upper limit of normal (ULN) per local
laboratory test, dosing should be delayed. All other study procedures, with the
exception of study drug administration, should be performed. At Visit 3, if Hgb
has increased by less than 2.0 g/dL from baseline (Visit 1) or Hgb value is
below the gender-specific ULN per local laboratory test, dosing should be
restarted at 0.3 mg/kg. At Visit 4, if Hgb has increased by less than 2.0 g/dL
from baseline (Visit 1) or
Hgb value is below the gender-specific ULN per local laboratory test, the dose
may be escalated to the target dose of 0.7 mg/kg.

Participants rolling over to the A011-12 study from an unblinded parent study
will continue sotatercept treatment at their current dose (SC) and, if they are
at dose < 0.7 mg/kg, they will have the opportunity to titrate up to a dose of
0.7 mg/kg (SC) per investigator discretion. The above guidelines for dose
escalation will be followed.

Participants will complete, at minimum, the first 5 consecutive visits at the
clinical site. In order to qualify for optional at home self-administration,
participants must meet the following criteria for the previous 3 consecutive
visits:
- Stable Hgb levels (within 2 g/dL, below the gender-specific upper ULN per
local laboratory test)
- Stable platelet count levels (within the normal range by local laboratory
test; if below the lower limit of normal, within 10% of the previous values)
Participants who meet these criteria qualify for optional self-administration
of sotatercept at home starting at Study Day 106 (±3 days) or later. Each
self--administration of sotatercept at home will be accompanied by a
phone call from the clinical investigative site to confirm proper storage,
dosing, and administration of sotatercept and to document concomitant
medications as well as incidence of any adverse events (AEs), medication
errors, accidental exposure of others, or product inquiries.
On-site visits will continue for participants who are ineligible for and opt
out of optional self-administration of sotatercept at home. For
participants eligible for and opting into self-administration of sotatercept at
home, quarterly on-site visits will be performed approximately every 3 months
according to the Schedule of Events in table 2, page 18 of the protocol.

Sotatercept, up to the target dose of 0.7 mg/kg.

Participation in the study requires amongst other the following of the patient:
- number of visits (in 4 years about 68 visits)
- procedures can be a burden, like right heart catherisation (RHC). However,
this procedure is only performed once, at the end of trial.
- during the study and till 112 days after the last dose, women are not allowed
to get pregnant
- if a patient is not eligible for self administration of sotatercept, the
patient has to visit the hospital every 3 weeks for an injection with
sotatercept
- adverse events (see E9 and E9a)

Currently, PAH cannot be treated and treatment only aims to relieve symptoms or
slow down clinical worsening. In general the disease shows progression.
In the PULSAR study Sotatercept was able to demonstrate hemodynamic and
functional improvements in these participants, including those
receiving maximal PAH therapy with double/triple drug combinations and
intravenous prostacyclin.
Through a novel mechanism of action, sotatercept may open up a new treatment
paradigm for PAH