Repeat administration of posoleucel was
generally well tolerated, with balanced safety across posoleucel
dosing groups and placebo
In Week 24 efficacy analysis, 39% (15/38) of
patients who received posoleucel experienced a ≥1-log viral load
reduction, more than double the placebo rate (14%; 2/14)
Posoleucel dose response was observed, with a
≥1-log viral load reduction in the biweekly dosing group of 50%
(10/20) vs. 28% (5/18) in the monthly dosing group and 14% (2/14)
in the placebo group
In the high viral load stratum (≥10,000
copies/mL), 69% (11/16) of patients who received posoleucel overall
and 75% (6/8) of patients in the biweekly dosing group, achieved a
≥1-log viral load reduction vs. 25% (1/4) of patients in the
placebo group
First demonstration of therapeutic potential of
posoleucel for solid organ transplant patients
Company to host investor webcast at 9:00 a.m.
EST today including Anil K. Chandraker, M.D., Director of Renal
Transplant Medicine, Brigham & Women’s Hospital
AlloVir, Inc. (Nasdaq: ALVR), a late-clinical stage allogeneic T
cell immunotherapy company, today announced positive final results
from a Phase 2 study of posoleucel, an investigational, allogeneic,
off-the-shelf, multi-virus-specific T cell (VST) therapy, being
studied for the treatment of BK viremia (BKV) in adult kidney
transplant recipients. The data support the safety and antiviral
activity of posoleucel in this population, which has no effective
BKV treatment options. In the randomized, double-blind,
placebo-controlled study, posoleucel was shown to be generally well
tolerated, with balanced safety across the two posoleucel dosing
groups and placebo. Patients who received posoleucel achieved a
clinically meaningful greater decline in BK viral load compared
with those receiving placebo. The study results showed an even
greater antiviral effect with posoleucel in patients with BK viral
load ≥10,000 copies/mL at screening and in the biweekly posoleucel
dosing group, identifying a dosing regimen and patient population
to advance into a future trial.
"BKV is one of the most feared transplant-associated viral
infections, due to the lack of available effective antiviral
therapies and its profoundly negative impact on transplant
outcomes,” said Anil K. Chandraker, M.D., Director of Renal
Transplant Medicine, Brigham and Women's Hospital, and principal
investigator of the posoleucel BKV treatment study. "The safety
profile of posoleucel and its antiviral activity, which is
amplified in high viral load patients who have the greatest unmet
need, suggest it could potentially offer a transformative treatment
option for kidney transplant patients with BK viremia.”
"This study is the first to evaluate a virus-specific T cell
therapy in solid organ transplant patients, with the primary goal
of exploring the safety of posoleucel treatment for BK viremia in
kidney transplant patients. We are pleased with the consistency of
posoleucel’s safety profile across solid and stem cell transplant
patient populations and with the important antiviral efficacy
results in kidney transplant patients at highest risk for
BKV-associated graft loss observed in this study," said Diana
Brainard, M.D., CEO, AlloVir. “We believe today's results are an
important and compelling milestone not just for AlloVir but for the
entire kidney transplant community."
Dr. Brainard continued, “These safety and efficacy data in solid
organ transplant patients provide important insights into the
potential of posoleucel, which is also being studied in our three
ongoing Phase 3 registrational trials in allo-HCT patients. We look
forward to working with regulatory authorities and transplant
specialists on our forward-looking clinical development strategy in
kidney transplant patients, and potentially other solid organ
transplant recipients."
This Phase 2 study evaluated the safety and efficacy of
posoleucel to treat BK viremia in adult kidney transplant
recipients with BK viral load between 350-10,000,000 copies/mL
(stratified by low (<10,000 copies/mL) or high (≥10,000
copies/mL) viral load at study screening). Sixty-one patients were
randomized 1:1:1 to receive one of two dosing regimens of
posoleucel – weekly administration of posoleucel for three weeks,
then every two weeks, or weekly administration of posoleucel for
three weeks, then once a month – or placebo over 12 weeks.
Following this dosing period, patients were followed through Week
24. Of the 61 enrolled patients, 58 patients completed the study
through Week 24; two patients were lost to follow-up and one
patient withdrew consent.
The primary endpoint of the study was safety and tolerability of
posoleucel versus placebo. Across all patients who received at
least a single dose of study drug, posoleucel was well tolerated.
The incidence and severity of adverse events were consistent with
the underlying patient population and background immunosuppression.
Low rates of infusion reactions were observed in patients receiving
posoleucel (2%) and those receiving placebo (5%). There were no
deaths or reports of graft versus host disease or cytokine release
syndrome. Emergence of donor-specific antibodies was uncommon and
occurred with similar frequency in patients receiving posoleucel
(7%) or placebo (5%). Three patients who received posoleucel were
reported to have acute rejection per biopsy report by a central
reader: one who was clinically diagnosed with, and successfully
treated for, renal tuberculosis, one who had rejection on a biopsy
prior to posoleucel dosing during the screening window, and one who
developed rejection at Week 22 of the trial. None of these cases
were assessed by the investigator as related to study drug.
The key secondary endpoint of the study was the change in BK
viral load in patients receiving posoleucel versus those receiving
placebo. The efficacy analysis excluded six patients in whom
significant reductions in immunosuppression were made immediately
prior to study entry. Posoleucel achieved greater viral load
reductions versus placebo consistently across multiple BK viral
load measures. This clinically meaningful treatment effect was
strongest among patients receiving posoleucel every two weeks and
among those with high viral loads. Antiviral responses among
posoleucel patients increased over time, with maximal responses
observed at Week 24. Renal function in this group remained stable
throughout the study, with a median change in estimated glomerular
filtration rate from baseline to Week 24 of 0 mL/min/1.73m2 in the
overall posoleucel group and 0 mL/min/1.73m2 in the placebo
group.
Summary of Week 24 Virologic Changes Among Patients With
Stable Immunosuppression Prior to Randomization*
Overall (N=52)
High VL Stratum (N=20)
PSL Biweekly (N=20)
PSL Monthly+ (N=18)
PSL Overall (N=38)
PBO (N=14)±
PSL Biweekly (N=8)
PSL Monthly (N=8)
PSL Overall (N=16)
PBO (N=4)
% Patients with ≥1 log10 copies/mL
reduction
50
28
39
14
75
63
69
25
BK VL change median log10 BKV DNA
copies/mL (min, max)
-0.9 (-2.1, 0.1)
-0.45 (-1.8, 0.5)
-0.6 (-2.1, 0.5)
-0.15 (-2.1, 0.3)
-1.4 (-2.1, 0.1)
-1.5 (-1.8, -0.2)
-1.4 (-2.1, 0.1)
-0.4 (-2.1, -0.01)
% Patients with ≥50% VL copies/mL
reduction
85
56
71
43
88
88
88
50
*PSL = posoleucel; PBO = placebo; VL =
viral load
+Excludes two patients who discontinued
study
±Excludes one patient who discontinued
study
The company plans to present comprehensive results from the BKV
Phase 2 study at a scientific congress later this year, and will
work with regulatory authorities and transplant specialists to
inform next steps for this program and AlloVir's broader solid
organ transplant strategy.
Investor Webcast Details
The company will host an investor webcast today at 9:00 a.m. EST
to discuss the study findings and the potential clinical impact of
using posoleucel to treat viral infections in the solid organ
transplant setting. The webcast will feature remarks from Dr.
Brainard and Dr. Chandraker.
A live audio webcast of the presentation will be available on
the Investors & Press section of the AlloVir website at
https://ir.allovir.com/events-and-presentations. An archived replay
of the presentation will be available on the website for 30 days
following the event.
About BK Viremia in Kidney Transplant Recipients
Due to the long-term immunosuppression required to prevent graft
rejection, solid organ transplant recipients are at high risk for
reactivating common viruses that are typically controlled by the
body's natural immune system. Uncontrolled, these viruses can have
devastating consequences.
BK viral infection poses a significant threat to kidney graft
survival. Approximately 80,000 kidney transplants are performed
each year globally, and the virus reactivates in up to 20% of these
patients. In patients who have reactivated BKV, a substantial
portion will develop high-level viremia, and approximately half of
those will develop BKV-associated nephropathy (BKVAN), which can
lead to decreased kidney survival and a return to end-stage renal
disease and dialysis. Consensus groups including the American
Society of Nephrology and the American Society of Transplantation
consider BK viral load of greater than or equal to 10,000 copies/mL
to be presumptive BKVAN.i
There are no approved or effective antiviral treatments for BK
viremia. The only approach to managing BK viremia is a reduction in
immunosuppression to allow the body's immune system to fight the
virus; this is typically triggered by a BK viral load of greater
than or equal to 10,000 copies/mL. However, this reduction in
immunosuppression can also lead to graft rejection and the
development of donor-specific antibodies, putting the success of
the kidney transplant at risk.
Data suggest that VST therapy may play a role in managing BK
viremia and BKVAN. Kidney transplant recipients who do not develop
BKVAN have been shown to have approximately 10-fold higher
BKV-specific T-cell responses versus those with BKVAN. Kidney
transplant recipients with BK viremia who develop robust
BKV-specific T-cell responses have also been shown to clear the
virus, while those who progressed to BKVAN required interventions
such as a reduction in immunosuppression.
About Posoleucel
AlloVir's lead product, posoleucel, is in late-stage clinical
development as an allogeneic, off-the-shelf, multi-virus specific
T-cell therapy targeting six viral pathogens in immunocompromised
individuals: adenovirus (AdV), BK virus (BKV), cytomegalovirus
(CMV), Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6) and JC
virus (JCV). In the positive Phase 2 proof-of-concept CHARMS study,
more than 90% of patients who failed conventional treatment and
received posoleucel demonstrated a complete or partial clinical
response based on predefined criteria, most with complete
elimination of detectable virus in the blood and resolution of
major clinical symptoms.
Based on the strength of the posoleucel Phase 2 data for both
treatment and prevention, the FDA has granted posoleucel
Regenerative Medicine Advanced Therapy (RMAT) designation for each
of the three indications being evaluated in Phase 3 clinical trials
– for the treatment of hemorrhagic cystitis (HC) caused by BKV, for
the treatment of AdV infection in adults and children following
allo-HCT, and for the prevention of clinically significant
infections and disease caused by posoleucel's six target viruses.
The FDA also granted posoleucel Orphan Drug Designation for the
treatment of virus-associated HC. The European Medicines Agency has
granted posoleucel PRIority MEdicines (PRIME) designation for the
treatment of serious infections with AdV, BKV, CMV, EBV and HHV-6,
and Orphan Medicinal Product designation as a potential treatment
of viral diseases and infections in patients undergoing HCT.
About AlloVir
AlloVir is a leading late clinical-stage allogeneic T cell
immunotherapy company with a focus on restoring natural immunity
against life-threatening viral diseases in pediatric and adult
patients with weakened immune systems. The company's innovative and
proprietary technology platforms leverage off-the-shelf,
allogeneic, single- and multi-virus-specific T cells for patients
with T cell deficiencies who are at risk from the life-threatening
consequences of viral diseases. AlloVir's technology and
manufacturing process enable the potential for the treatment and
prevention of a spectrum of devastating viruses with each single
allogeneic cell therapy. The company is advancing multiple mid- and
late-stage clinical trials across its product portfolio. For more
information, visit www.allovir.com or follow us on Twitter or
LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended, including, without limitation, statements
regarding the potential efficacy of posoleucel as a treatment for
BK viremia, AlloVir's development plans and the regulatory status
of AlloVir's product candidates, the planned conduct of its
preclinical studies, and clinical trials and its prospects for
success in those studies and trials, and its strategy, business
plans and focus. The words "may," "will," "could," "would,"
"should," "expect," "plan," "anticipate," "intend," "believe,"
"estimate," "predict," "project," "potential," "continue," "target"
and similar expressions are intended to identify forward-looking
statements, although not all forward-looking statements contain
these identifying words. Any forward-looking statements in this
press release are based on management's current expectations and
beliefs and are subject to a number of risks, uncertainties, and
important factors that may cause actual events or results to differ
materially from those expressed or implied by any forward-looking
statements contained in this press release, including, without
limitation, those related to the potential of posoleucel as a
treatment for BKV, the potential of posoleucel as a transformative
treatment option for kidney transplant patients with BK viremia,
AlloVir's financial results, the timing for the initiation and
successful completion of AlloVir's clinical trials of its product
candidates, whether and when, if at all, AlloVir's product
candidates will receive approval from the U.S. Food and Drug
Administration, or FDA, or other foreign regulatory authorities,
competition from other biopharmaceutical companies, the impact of
the COVID-19 pandemic on AlloVir's product development plans,
supply chain, and business operations and other risks identified in
AlloVir's SEC filings, including but not limited to the risks
discussed in AlloVir's Annual Report on Form 10-K for the year
ended December 31, 2021, and in our other filings with the SEC.
AlloVir cautions you not to place undue reliance on any
forward-looking statements, which speak only as of the date they
are made. AlloVir disclaims any obligation to publicly update or
revise any such statements to reflect any change in expectations or
in events, conditions, or circumstances on which any such
statements may be based, or that may affect the likelihood that
actual results will differ from those set forth in the
forward-looking statements. Any forward-looking statements
contained in this press release represent AlloVir's views only as
of the date hereof and should not be relied upon as representing
its views as of any subsequent date.
_______________________
i Imlay et al. CID 2022.
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version on businesswire.com: https://www.businesswire.com/news/home/20230215005300/en/
Media and Investor Contact: Sonia Choi AlloVir
schoi@allovir.com
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