Clinical data

PATHFNDR-2: uncontrolled/treatment naïve

PALSONIFY was studied in two phase 3, randomized, placebo-controlled clinical trials¹

A 24-week study that evaluated adults with acromegaly who were biochemically uncontrolled, including treatment naïve.¹

Rapid and reliable biochemical control

Consistent symptom control

Sustained IGF-1 control

Study design

Safety

IGF-1 reduction observed within weeks¹

IGF-1 control of ≤1.0 × ULN achieved in 56% of patients taking PALSONIFY at week 24 vs only 5% of patients taking placebo (primary endpoint, P<0.0001).

Mean IGF-1 change from baseline by visit^1,7

Exploratory endpoint

Chart showing mean IGF-1 change from baseline by visit; IGF-1 normalization for PALSONIFY patients in as little as 2 weeks

93% of patients taking PALSONIFY had reductions in IGF-1¹⁴

Only 1 patient taking PALSONIFY received rescue therapy vs 13 patients taking placebo¹⁴*

*Rescue therapy with standard-of-care treatment was initiated if a participant had evidence of uncontrolled acromegaly based on IGF-1 levels and symptoms.¹
BL=baseline; IGF-1=insulin-like growth factor 1; ULN=upper limit of normal.

Mean IGF-1 change from baseline to week 24 by patient type¹⁴

Exploratory endpoint

Bar graph showing the mean IGF-1 change from baseline to week 24 by patient type

PALSONIFY reduced IGF-1, regardless of treatment history¹⁴

Reductions occurred across all patient types and were maintained through week 24¹⁴

*Nominal P≤0.0001; should not be interpreted as establishing clinical significance.¹⁴
†Nominal P<0.0001; should not be interpreted as establishing clinical significance.¹⁴
LS=least squares.

PALSONIFY achieved GH control¹⁴*

57%

of patients taking PALSONIFY achieved target GH of <1.0 ng/mL at week 22 vs 18% of patients taking placebo (P<0.0001).

*Secondary endpoint.
GH=growth hormone.

Consistent symptom control maintained with PALSONIFY¹⁴

Symptom control assessed using the Acromegaly Symptom Diary (ASD), a novel PRO tool¹²

Significantly improved overall symptom control vs a worsening of symptoms with placebo¹⁴*

Mean change in ASD score by symptom from baseline to week 24^1,14

Exploratory endpoint

Bar graph showing the mean change in ASD score by symptom from baseline to week 24

PALSONIFY reduced the severity of a range of acromegaly symptoms^1,14

*Symptoms for patients taking PALSONIFY improved based on an ASD score of -2.7 vs symptoms worsening based on an ASD score of 2.8 for patients taking placebo (P=0.004).¹⁴
†Nominal P<0.01; should not be interpreted as establishing clinical significance.¹⁴
^‡Nominal P<0.05; should not be interpreted as establishing clinical significance.¹⁴
PRO=patient-reported outcome.

The majority of patients stayed on PALSONIFY and maintained IGF-1 control in an extension study^10,13

Randomized control trial

Open-label extension study: PATHFNDR-2

High retention through trial¹⁴

95%

of patients completed the PATHFNDR-2 randomized control period

Strong preference to stay on therapy¹⁴

97%

of eligible patients who completed the randomized control period opted to continue on or switch to PALSONIFY in the open-label extension study*

Control maintained long term¹⁴

93%

of patients who achieved IGF-1 normalization at the end of the randomized control period maintained biochemical control at month 19 in the extension study†

*The starting dose of PALSONIFY in the extension study was 20 mg/day. Patients could be titrated to 40 mg/day based on tolerability at week 2 of the extension study, with an optional titration to 60 mg/day based on IGF-1. Adjunctive acromegaly medication (eg, cabergoline, pegvisomant) was permitted beginning at week 24 of the extension study, at the investigator’s discretion.¹⁵
†Among patients who achieved IGF-1 normalization at week 24 of the randomized control period and completed the week 60 visit of the extension study, 27/29 (93%) maintained IGF-1 normalization at week 60 of the extension study.¹⁰

Rigorously studied in patients who were medically untreated (including treatment naïve) or washed out^1,14

Image showing the study design of the PATHFNDR-2 clinical trial

Patient strata defined

Not medically treated

Treatment naïve: no prior medical therapy and pituitary surgery at least 3 months prior to screening^1,14
Previously treated: had prior treatment but stopped on their own at least 4 months before screening^1,14

Washed out: controlled on first-generation SRLs (octreotide or lanreotide) for at least 3 months but paused therapy specifically for the screening period (12-16 weeks).^14,15

Primary endpoint: proportion of patients with IGF-1 ≤1.0 × ULN at week 24¹

Results: primary and all secondary endpoints were met^1,14*

*Secondary endpoints included change from baseline in IGF-1 (measured as × ULN) at end of randomized treatment; proportion of patients who achieved IGF-1 <1.3 × ULN at end of randomization; change from baseline in total ASD score at end of randomized treatment; and proportion of patients with mean 5-sample GH <1.0 ng/mL at week 22.¹⁴
SRLs=somatostatin receptor ligands.

Well-tolerated safety profile¹

The safety of PALSONIFY was evaluated in 111 adults with acromegaly who were biochemically uncontrolled, including treatment naïve, at randomization in the PATHFNDR-2 study.

Adverse reactions reported for PALSONIFY and Placebo groups
Adverse reaction*	PALSONIFY (n=54) n (%)	Placebo (n=57) n (%)
Diarrhea	18 (33)	8 (14)
Abdominal pain†	10 (19)	3 (5)
Nausea	5 (9)	1 (2)
Sinus bradycardia	4 (7)	0
Hyperglycemia^‡	4 (7)	1 (2)

*Adverse reactions occurring in ≥5% of PALSONIFY-treated participants and 5% greater incidence than placebo-treated participants during the randomized control period.
†Abdominal pain also includes abdominal discomfort.
^‡Hyperglycemia also includes impaired fasting glucose and diabetes mellitus.

Key safety outcomes from the randomized control period of the PATHFNDR-2 clinical study

Mild to moderate AEs¹⁴

The most commonly reported AEs (diarrhea, headache, abdominal pain, and arthralgia) were generally mild to moderate in intensity.
GI AEs resolved¹⁴

GI AEs were mild or moderate and resolved without discontinuing PALSONIFY.
Low discontinuation rate¹⁴

Only 1 patient who discontinued PALSONIFY to receive rescue therapy met the full rescue criteria.*
Tumor control¹⁴

A reduction in tumor volume of >20% was observed in 4 patients (11.8%) taking PALSONIFY and no patients taking placebo. No patients had a newly visible tumor, and no clinically significant increases in tumor volume were observed in the PALSONIFY group.†

*Rescue medication (iSRL) was administered if a patient had 2 consecutive IGF-1 levels ≥1.5 × ULN at the highest dose of study medication (60 mg/day) and exacerbation of acromegaly clinical signs and symptoms. Only 1 patient in the study met the full rescue criteria. Another patient in the study received rescue therapy at the investigator’s discretion due to the presence of symptoms.¹⁴
†Clinically significant changes in pituitary tumor volume were defined as increases or decreases of >20% from baseline to week 24 as measured by MRI.¹⁴
AEs=adverse events; GI=gastrointestinal; iSRL=injected somatostatin receptor ligand; MRI=magnetic resonance imaging.

View PATHFNDR-1 data

PATHFNDR-2: uncontrolled/treatment naïve

PALSONIFY was studied in two phase 3, randomized, placebo-controlled clinical trials¹

IGF-1 reduction observed within weeks¹

PALSONIFY achieved GH control¹⁴*

Consistent symptom control maintained with PALSONIFY¹⁴

Significantly improved overall symptom control vs a worsening of symptoms with placebo¹⁴*