Clinical data

PATHFNDR-1: switching from SRL injections

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

A 36-week study that evaluated adults with acromegaly who were biochemically controlled and switching from octreotide or lanreotide depot injections.¹

Rapid and reliable biochemical control

Consistent symptom control

Sustained IGF-1 control

Study design

Safety

Seamlessly maintained IGF-1 control in patients who switched from SRL injections^1,2*

Percentage of patients maintaining normal IGF-1 at week 36^1,2

Primary endpoint

PALSONIFY maintained IGF-1 ≤1.0 × ULN¹

Normal IGF-1 defined as ≤1.0 × ULN¹

*Octreotide or lanreotide.¹
IGF-1=insulin-like growth factor 1; SRL=somatostatin receptor ligand; ULN=upper limit of normal.

mean IGF-1 by visit^2,11*

Exploratory endpoint

Chart showing mean IGF-1 by visit; PALSONIFY patients' mean IGF-1 stayed below 1.0xULN through week 36

Only 1 patient taking PALSONIFY had an IGF-1 >1.1 × ULN at EOT²

*Last observation carried forward for patients who received rescue medication or discontinued from the study.¹¹
EOT=end of treatment (week 36 or last assessment before rescue).^2,11

PALSONIFY maintained GH control²*

87%

of patients taking PALSONIFY maintained target GH of <1.0 ng/mL at week 34 vs 28% of patients taking placebo (P=0.0003).

*Secondary endpoint.
GH=growth hormone.

Consistent symptom control maintained with PALSONIFY⁷

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

Mean change in ASD score by symptom from baseline to week 36^2,7

Exploratory endpoint

Bar graph showing the mean change in ASD score by symptom from baseline to week 36

PALSONIFY reduced symptom severity vs placebo⁷†

*Nominal P<0.05; should not be interpreted as establishing clinical significance.⁷
†Secondary endpoint. The change from baseline to week 36 in total ASD score showed a statistically significant improvement of -0.6 for patients who took PALSONIFY compared to a worsening of 4.6 for patients on placebo (P=0.0216).⁷
PRO=patient-reported outcome.

Post hoc analysis showed reduced symptom variability after switching from iSRLs to PALSONIFY¹¹*

CHANGE IN OVERALL SYMPTOM EXACERBATION FREQUENCY FROM iSRL BASELINE IN PATIENTS WHO SWITCHED TO PALSONIFY (n=22)¹¹

Bar graph showing the overall symptom exacerbation frequency in patients switching from iSRLs to PALSONIFY

PALSONIFY demonstrated improved symptom stability in biochemically controlled patients¹¹

*Methods: Post hoc symptom analyses included PATHFNDR-1 participants who had adequate ASD data (at least 4 completed days during the screening period) and did not require rescue with iSRLs. Symptom exacerbation was defined as a ≥2-point increase for any individual symptom score, comparing a 2-day average to the previous 2-day average.¹¹
†Exploratory post hoc analysis; should not be interpreted as establishing clinical significance.¹¹
iSRLs=injected somatostatin receptor ligands.

Change from iSRL baseline in individual symptom exacerbation frequencies in patients treated with PALSONIFY¹¹

Bar graph showing the change from iSRL baseline in individual symptom exacerbation frequencies.

Patients reported greater consistency across symptoms¹¹

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-1

High retention through trial²

98%

of patients completed the PATHFNDR-1 randomized control period

Strong preference to stay on therapy²

93%

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

Control maintained long term^1,10

96%

of patients who maintained normal IGF-1 at the end of the randomized control period maintained biochemical control at month 22 in the extension study†

*The starting dose of PALSONIFY in the extension study was 40 mg/day. The dose could be titrated up to 60 mg/day based on IGF-1 or titrated down to 20 mg/day based on tolerability.⁸
†Among patients who achieved IGF-1 normalization at week 36 of the randomized control period and completed the week 60 visit of the extension study, 22/23 (96%) maintained IGF-1 normalization at week 60 of the extension study.¹⁰

Rigorously studied in patients who were biochemically controlled on SRL injections^1,2

Image showing the study design of the PATHFNDR-1 clinical trial

Primary endpoint: proportion of patients with IGF-1 ≤1.0 × ULN at week 36¹

Results: primary and all secondary endpoints were met^1,2*

*Secondary endpoints included change from baseline in IGF-1 (measured as × ULN) at end of randomized treatment or the last assessment before rescue medication; 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 34 among those with mean 5-sample GH <1.0 ng/mL during screening.²
AEs=adverse events.

Well-tolerated safety profile¹

The safety of PALSONIFY was evaluated in 58 adults with acromegaly who had switched from SRL injections during the randomized control period of the PATHFNDR-1 study.

Adverse reactions reported for PALSONIFY and Placebo groups
Adverse reaction*	PALSONIFY (n=30) n (%)	Placebo (n=28) n (%)
Diarrhea	7 (23)	3 (11)
Nausea	4 (13)	1 (4)
Decreased appetite†	3 (10)	0
Palpitations	2 (7)	0
Gastroenteritis	2 (7)	0

*Adverse reactions occurring in ≥5% of PALSONIFY-treated participants and 5% greater incidence than placebo-treated participants during the randomized control period.
†Decreased appetite also includes early satiety.

Key safety outcomes from the randomized control period of the PATHFNDR-1 clinical study

Mild to moderate AEs²

The most commonly reported AEs (arthralgia, headache, diarrhea, and abdominal pain) were mild to moderate in intensity.
GI AEs resolved²

GI AEs were resolved without discontinuing PALSONIFY, consistent with the typical course of SRL-related GI AEs.
Low discontinuation rate²

Only 1 patient who discontinued PALSONIFY to receive rescue therapy met the full rescue criteria.*
No tumor changes²

Patients did not develop any new visible tumors, and there were no tumor volume increases or decreases deemed clinically significant.†

*Rescue medication (patient’s prior iSRL) was administered if a patient had 2 consecutive IGF-1 levels ≥1.3 × 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 due to AEs that were not considered to be related to PALSONIFY.²
†Clinically significant changes in pituitary tumor volume were defined as increases or decreases of >25% from baseline to week 36 as measured by MRI.²
GI=gastrointestinal; MRI=magnetic resonance imaging.

View PATHFNDR-2 data

A new tool was developed to monitor acromegaly symptoms in clinical trials¹²

The Acromegaly Symptom Diary (ASD) is a novel patient-reported outcome (PRO) tool. Built in accordance with FDA guidance, the ASD offers quantifiable insight into changes in acromegaly symptoms. It was designed to assess symptom severity and capture the day-to-day symptom burden that traditional biochemical markers may overlook.

The ASD in PATHFNDR studies

The ASD was used in PALSONIFY clinical trials to evaluate symptom control over time. It was completed daily during screening and during study treatment. Patients rated each symptom on a scale from 0 (no symptom) to 10 (worst symptom).

The total ASD score is the weekly average of daily scores (the sum of a scored item over 1 week divided by the number of days on which the item was completed).

The ASD tool measured symptom severity in 7 categories:

Headache
Joint pain
Sweating
Fatigue