GNW-Adhoc: Idorsia reacquires the world-wide rights to aprocitentan

^Ad hoc announcement pursuant to Art. 53 LR
* Aprocitentan, Idorsia's oral, dual endothelin receptor antagonist is
currently under review with health authorities for the treatment of patients
with resistant hypertension.
* Idorsia will pay Janssen a conditional consideration up to a total cap of
CHF 306 million
* Idorsia is initiating activities to determine the best approach to maximize
the value of aprocitentan.
Allschwil, Switzerland - September 6, 2023
Idorsia Ltd (SIX: IDIA) today announced that it has entered into an agreement
with Janssen Biotech Inc., one of the Janssen Pharmaceutical Companies of
Johnson & Johnson, for the return of rights for aprocitentan to Idorsia. In
return, Idorsia is committed to pay up to 306 million Swiss francs, subject to
marketing application approval by the US FDA and Europe's EMA.
Jean-Paul Clozel, CEO of Idorsia, commented:
"I'm happy that we have come to an agreement for the return of aprocitentan to
Idorsia. Aprocitentan has demonstrated significant and clinically meaningful
sustained blood pressure lowering benefits with a good safety profile,
particularly suited to the high-risk patient population with resistant
hypertension. Revolutionizing the use of endothelin receptor antagonism is
something the team at Idorsia knows all about. We will now determine the best
approach to maximizing the value of our exciting new anti-hypertension therapy."
The founding team at Idorsia brought the first oral, dual endothelin receptor
antagonist (ERA) to market, followed by the discovery, development, and launch
of a next generation oral, dual ERA. The team will now evaluate options for
realizing the value which the company has created by successfully developing
aprocitentan, the first anti-hypertensive therapy which works via a new
mechanism of action in 30 years.
About the agreement
Idorsia will reacquire the development and commercialization rights for
aprocitentan from Janssen. In return, Idorsia will pay Janssen a conditional
consideration up to a total cap of CHF 306 million, depending on Idorsia's
revenues, as follows:
* 30% of any consideration received by Idorsia from a potential out-licensing
or divestment of aprocitentan,
* 10% of any consideration received by Idorsia from a potential out-licensing
or the divestment of any other Idorsia product, following the first approval
of aprocitentan, and
* low- to mid-single digit royalties on total group product net sales,
beginning from the quarter after first aprocitentan approval.
Janssen funding obligations to aprocitentan cease at the effective date of the
agreement. Janssen licenses to aprocitentan IP (excluding pulmonary
hypertension) will terminate and Janssen will transfer the brand name and
relating commercial materials to Idorsia. Janssen will retain licenses in the
pulmonary hypertension field.
The agreement also eliminates the revenue-sharing agreement in respect of
ponesimod.
The agreement will be effective following receipt of the clearance relating to
the United States Hart-Scott Rodino Antitrust Improvements Act of 1976.
André C. Muller, Chief Financial Officer, commented:
"If aprocitentan is approved in the US and Europe as we expect, Idorsia would
have an additional product in its portfolio giving the company more strategic
flexibility, and potentially allows Janssen to recoup over time their investment
in aprocitentan."
About the regulatory status of aprocitentan
A new drug application (NDA) for aprocitentan was filed with the US FDA in
December 2022 (Prescription Drug User Fee Act (PDUFA) current date: December
19, 2023), and the market authorisation application (MAA) was submitted to the
EMA at the end of January 2023.
Jean-Paul Clozel, concluded:
"The review process with the US FDA is progressing well, though it is likely to
require an extension to the review period of up to 3 months as the company will
provide additional Risk Evaluation and Mitigation Strategy (REMS) materials to
support a streamlined REMS which is designed specifically for patients taking
aprocitentan."
About aprocitentan in resistant hypertension
Full results from the PRECISION study were published in November 2022 in The
Lancet "A randomized controlled trial of the dual endothelin antagonist
aprocitentan for resistant hypertension
(https://www.thelancet.com/journals/lancet/article/PIIS0140-
6736(22)02034-7/fulltext)". More details and commentary can be found in the
dedicated press release (https://www.idorsia.com/investors/news-and-
events/media-release-details?newsId=2869821) and an investor webcast
(https://www.idorsia.com/investors/news-and-events/Apro-session-AHA-2022)
featuring Prof. Markus Schlaich, an investigator in PRECISION.
Patients with uncontrolled blood pressure are at risk of major cardiovascular
events.(1) These risks are even higher for patients whose blood pressure is
uncontrolled despite treatment with three or more antihypertensives(2), known as
resistant hypertension(3,4). It has been more than 30 years since a new anti-
hypertensive therapy working by a new mechanism has been brought to patients. By
targeting a currently unopposed pathophysiologic pathway, aprocitentan
represents a potential novel, effective, and well-tolerated treatment for
resistant hypertension.
Notes to the editor
The endothelin system in systemic hypertension
Endothelin-1 (ET-1) is a potent vasoconstrictor that also induces neurohormonal
activation, vascular hypertrophy and remodeling, cardiac hypertrophy and
fibrosis, and endothelial dysfunction. In hypertension, both ET(A) and ET(B)
receptors mediate harmful effects of ET-1.(4) As a vasoconstrictor, co-mitogenic
agent, linking pulse pressure and vascular remodeling, and mediator of
aldosterone and catecholamine release, endothelin is a key player in
hypertension and end-organ damage.(5,)(6)
About difficult-to-control (resistant) hypertension
Hypertension (high blood pressure) is one of the most common cardiovascular risk
factors, and its prevalence continues to rise. According to a recent study,
there are more than 1.3 billion people living with hypertension worldwide(6) - a
startling number, which has almost doubled in the past 40 years. Left
uncontrolled, people have a greater risk of life-threatening conditions such as
heart attack, stroke, and chronic kidney disease.(7)
Patients with hypertension can often successfully control their blood pressure
by combining a healthier lifestyle with effective medication. However,
approximately 10% of patients have difficult-to-control hypertension where the
blood pressure remains high despite receiving at least three antihypertensive
medications of different pharmacological classes, including a diuretic, at
optimal doses,(3)(,)(8) (also categorized in hypertension guidelines and the
medical community as having resistant hypertension).
The endothelin pathway has been implicated in the pathogenesis of hypertension,
especially in volume- and salt-dependent forms, which are a common feature in
patients with resistant hypertension. The endothelin pathway has not been
targeted by existing anti-hypertensive therapies until now, thereby leaving this
relevant pathophysiologic pathway unopposed with currently available
medications.(3,9,10) The endothelin system is also activated in patients prone
to developing resistant hypertension, such as Black or African American
patients, patients with obesity or obstructive sleep apnea,(1)(1)(-1)(3) and in
comorbid conditions frequently associated with resistant hypertension such as
diabetes and chronic kidney disease.(1)(4)(-1)(7)
About aprocitentan
Aprocitentan is an investigational, novel, oral, dual endothelin receptor
antagonist (ERA), which potently inhibits the binding of ET-1 to ET(A) and ET(B)
receptors. Aprocitentan has a low potential for drug-drug interaction and a
mechanism of action that is ideally suited for the pathophysiology of resistant
hypertension.
About PRECISION(18,19) (NCT03541174
(https://www.clinicaltrials.gov/ct2/show/NCT03541174))
PRECISION was a multicenter, blinded, randomized, parallel-group, Phase 3 study,
which was performed in hospitals or research centers in Europe, North America,
Asia, and Australia. Patients were eligible for randomization if their sitting
systolic blood pressure was 140 mm Hg or higher despite taking standardized
background therapy consisting of three antihypertensive drugs, including a
diuretic. The study consisted of three sequential parts: Part 1 was the 4-week
double-blind, randomized, and placebo-controlled part, in which 730 patients
were randomized to aprocitentan 12.5 mg (n=243), aprocitentan 25 mg (n=243), or
placebo (n=244) in a 1:1:1 ratio; Part 2 was a 32-week single (patient)-blind
part, in which all patients received aprocitentan 25 mg (n=704); and Part 3 was
a 12-week double-blind, randomized, and placebo-controlled withdrawal part, in
which patients were re-randomized to aprocitentan 25 mg (n=307) or placebo
(n=307) in a 1:1 ratio. The primary and key secondary endpoints were changes in
unattended office systolic blood pressure from baseline to week 4 and from
withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h
ambulatory blood pressure changes.
At baseline, 69.2% of patients were obese or severely obese, 54.1% had diabetes,
22.2% had stage 3-4 chronic kidney disease and 19.6% had congestive heart
failure. 63% of randomized patients were receiving at least 4 anti-hypertensive
therapies at screening.
Key PRECISION findings(19)
The least square mean change in office SBP at 4 weeks was -15.3 mmHg for
aprocitentan 12.5 mg, -15.2 mmHg for 25 mg, and -11.5 mmHg for placebo, for a
difference versus placebo of -3.8 mmHg (p=0.0042) and -3.7 mmHg (p=0.0046),
respectively. Office diastolic blood pressure (DBP) also decreased with both
aprocitentan doses compared to placebo (-3.9 mmHg for the 12.5 mg dose and -4.5
mmHg for the 25 mg dose). Office SBP and DBP were maintained during Part 2 in
patients previously receiving aprocitentan and decreased within the first 2
weeks of Part 2 before stabilizing in those previously receiving placebo. In
Part 3, office SBP after 4 weeks of withdrawal (the key secondary endpoint)
increased significantly with placebo compared to aprocitentan (5.8 mmHg;
p°

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