- Issued: 4 March 2024, London
UK
ViiV
Healthcare presents phase I clinical trial findings of a
cabotegravir long-acting injectable investigational formulation
allowing at least four months between doses
· Data show for the first time a new ultra long-acting
cabotegravir formulation (CAB-ULA) that doubles the current dosing
interval
· Pharmacokinetic, tolerability and safety data supports moving
CAB-ULA to the next stage of clinical development
GSK plc (LSE/NYSE: GSK) announced
that ViiV Healthcare, the global specialist
HIV company majority owned by GSK, with Pfizer and Shionogi as
shareholders, today announced positive findings from its phase I
study showing that an investigational formulation of cabotegravir,
known as cabotegravir ultra long-acting (CAB-ULA), can be dosed at
intervals of at least four months. This is the company's first step
towards delivering ultra long-acting injectable HIV treatment and
prevention medicines that would potentially enable people to have
at least four months between visits to the clinic.
Data also showed that the
intramuscular dosing of CAB-ULA has a safety and pharmacokinetic
(PK) profile that supports a longer dose interval.[1] These findings were presented today at the
Conference
on Retroviruses and Opportunistic Infections (CROI
2024)[2], in Denver, Colorado.
ViiV Healthcare is conducting a
registrational study of CAB-ULA in 2024 to further evaluate its use
for the prevention of HIV in adults. Future areas of study will
include its potential use in combination with other medicines as a
complete, ultra long-acting HIV treatment regimen.
Kimberly Smith, M.D., MPH, Head of Research & Development
at ViiV Healthcare, said: "The HIV
community has told us of their desire for longer-acting medicines
that can help alleviate the burden of daily treatment. ViiV
Healthcare is a pioneer and leader in the development of
long-acting HIV medicine, having already brought innovations
through injectable therapies to the HIV community. This new
formulation of cabotegravir (CAB-ULA) with a higher concentration
and at least double the half-life puts us on the path toward
delivering dosing at every four months for HIV treatment and
PrEP."
The ongoing, open-label,
single-dose, dose-escalation phase I study in 70 healthy adults
evaluated the safety and PK of two different formulations of
cabotegravir and their potential for less frequent dosing. To
evaluate the long-acting potential of these regimens, their PK
profiles were compared against the 200 mg/mL intramuscular
formulation of cabotegravir (CAB200), which is currently approved
for the prevention of HIV by itself or for the treatment of HIV
(when combined with rilpivirine).
One part of the study evaluated
single doses of CAB-ULA administered subcutaneously (SC) in 16
participants or intramuscularly (IM) in 32 participants at doses of
800 mg, 1200 mg, and 1600 mg. The maximum observed plasma
concentration of CAB-ULA, regardless of route of administration,
was lower than CAB200 IM at the same dose level, indicating slower
absorption of CAB-ULA. The projected half-life (measure of time the
drug stays in the body) of CAB-ULA (SC) and CAB-ULA (IM) was six
times greater and two times greater, respectively, than the
half-life of CAB200 IM. PK simulations enabled researchers to
predict that a 1600 mg/3mL IM dose of CAB-ULA administered every
four months or greater could potentially achieve a similar level of
medicine exposure compared to the approved 600 mg/3mL IM dose of
CAB200, which is administered every two months.
Administration of CAB-ULA was well
tolerated with no adverse events (AEs) leading to participant study
discontinuation. All participants who received SC doses of CAB-ULA
reported injection site reactions (ISRs), while 22/32 who received
IM doses reported ISR events. The majority of IM ISRs were mild
pain (grade 1) that lasted less than 7 days. Even though dosing in
this study was higher than the currently approved CAB200 IM, the
CAB-ULA IM ISR profile appeared comparable to the established
CAB200 IM ISR profile.
Kelong Han, Ph.D., Primary Study
Investigator, GSK, said: "These findings
suggest CAB-ULA has a PK profile with the potential for a dosing
interval of at least four months, which is longer than any
currently approved HIV prevention option. We look forward to the
further clinical development of this promising medicine. As we look
to the future, further advancements in longer acting medicines have
the potential to revolutionise how HIV is treated and
prevented."
A second part of the study evaluated
a variety of doses of CAB200 administered by SC injection in 22
participants in combination with recombinant human hyaluronidase
PH20 (rHuPH20), an enzyme that enables a large amount of fluid to
be rapidly delivered by subcutaneous injection. In this part,
rHuPH20 (10,000 IU) was administered first, followed by CAB200 at
800 mg, 1600 mg, and 3200 mg doses.
Following co-administration of
CAB200 + rHuPH20, the observed CAB plasma
concentration increased proportionally with dose, and the maximum
observed CAB plasma concentration was higher than CAB200 IM alone
at the same dose level, indicating an increased initial absorption
rate of the medicine. The mean half-life for the three different
CAB200 + rHuPH20 doses was similar to CAB200 IM alone, indicating a
low potential to achieve less frequent dosing.
ISRs occurred in all participants
with a dose-related trend for increased ISR grades. One participant
who received the highest CAB200 dose (3200mg) SC + rHuPH20
experienced a drug-related serious AE of injection site erythema
with necrosis. Based on these combined findings, ViiV
Healthcare is no longer pursuing CAB 200 SC + rHuPH20 for ultra
long-acting dosing.
About ViiV Healthcare
ViiV Healthcare is a global
specialist HIV company established in November 2009 by GSK (LSE:
GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances in
treatment and care for people living with HIV and for people who
are at risk of acquiring HIV. Shionogi became a ViiV shareholder in
October 2012. The company's aims are to take a deeper and broader
interest in HIV and AIDS than any company has done before and take
a new approach to deliver effective and innovative medicines for
HIV treatment and prevention, as well as support communities
affected by HIV.
For more information on the company,
its management, portfolio, pipeline, and commitment, please visit
viivhealthcare.com.
About GSK
GSK is a global biopharma company
with a purpose to unite science, technology, and talent to get
ahead of disease together. Find out more at gsk.com.
ViiV enquiries
|
|
|
|
Media:
|
Ken Inchausti
Rachel Jaikaran
|
+1 732 690 6938
+44 (0) 78 2352 3755
|
(Colorado)
(London)
|
|
Audrey Abernathy
|
+ 1 919 605 4521
|
(North Carolina)
|
GSK
enquiries
|
|
|
|
Media:
|
Tim Foley
|
+44 (0) 20 8047 5502
|
(London)
|
|
Sarah Clements
|
+44 (0) 20 8047 5502
|
(London)
|
|
Kathleen Quinn
|
+1 202 603 5003
|
(Washington DC)
|
|
Alison Hunt
|
+1 540 742 3391
|
(Washington DC)
|
|
|
|
|
Investor Relations:
|
Nick Stone
|
+44 (0) 7717 618834
|
(London)
|
|
James Dodwell
|
+44 (0) 20 8047 2406
|
(London)
|
|
Mick Readey
|
+44 (0) 7990 339653
|
(London)
|
|
Josh Williams
|
+44 (0) 7385 415719
|
(London)
|
|
Camilla Campbell
|
+44 (0) 7803 050238
|
(London)
|
|
Steph Mountifield
|
+44 (0) 7796 707505
|
(London)
|
|
Jeff McLaughlin
|
+1 215 751 7002
|
(Philadelphia)
|
|
Frannie DeFranco
|
+1 215 751 4855
|
(Philadelphia)
|
Cautionary statement regarding forward-looking
statements
GSK cautions
investors that any forward-looking statements or projections made
by GSK, including those made in this announcement, are subject to
risks and uncertainties that may cause actual results to differ
materially from those projected. Such factors include, but are not
limited to, those described under Item 3.D "Risk factors" in the
company's Annual Report on Form 20-F for 2022, and Q4 Results for
2023.
Registered in England & Wales:
GSK plc
ViiV Healthcare Limited
No. 3888792
No. 06876960
Registered Office:
GSK
plc
ViiV Healthcare Limited
980 Great West Road
GSK
Medicines Research Centre
Brentford, Middlesex
Gunnels Wood Road,
Stevenage
United Kingdom
United Kingdom
TW8 9GS
SG1 2NY