FDA Grants De Novo Designation for Adaptive Biotechnologies’ clonoSEQ Assay to Detect and Monitor Minimal Residual Disease (MRD) in Patients with Multiple Myeloma and Acute Lymphoblastic Leukemia

clonoSEQ is a first-in-class NGS assay and the first and only
FDA-cleared MRD assay for any lymphoid cancer


SEATTLE–(BUSINESS WIRE)–#MRD–Adaptive Biotechnologies® announced today that the U.S. Food
and Drug Administration (FDA) has granted De Novo designation for the
clonoSEQ® Assay to detect and monitor minimal residual
disease (MRD) in patients with multiple myeloma (MM) and B-cell acute
lymphoblastic leukemia (ALL) using DNA from a patient’s bone marrow
sample. The clearance of clonoSEQ marks several “firsts” for patients
and for the FDA. The clonoSEQ Assay represents a first-in-class MRD
assay that uses next-generation sequencing (NGS) technology to assess
disease burden, representing an important additional use of NGS in
cancer. clonoSEQ is the first and only assay to be cleared by the FDA
for MRD assessment in any lymphoid cancer and the first FDA-cleared
diagnostic assay powered by immunosequencing. It is also a major
milestone for Adaptive Biotechnologies as the first regulatory clearance
for the company’s proprietary (NGS) platform for immune system profiling.

MRD refers to the small number of cancer cells that can remain in a
patient’s body after treatment, which often cause no signs or symptoms
but eventually can lead to recurrence of the disease. These residual
cells can be present at very low levels and require highly sensitive
tests to identify them. Even very small amounts of MRD can have a
profound effect on treatment success and patient outcomes. A test that
can reliably determine the presence and amount of residual disease at
very low levels can be used by physicians in conjunction with other
clinical information to predict treatment outcomes, guide management
decisions and improve patient care.

MRD testing provides patients with real-time insights about their
response to therapy or the depth of their remission, therefore the MMRF
is deeply committed to this important advancement in patient care,” said
Paul Giusti, president and chief executive officer, Multiple Myeloma
Research Foundation (MMRF). “The sensitivity of the test is extremely
important, as the number of cells remaining after treatment has been
linked to patient outcomes. This clearance provides patients and
physicians with access to a highly sensitive, standardized MRD test that
can be an important tool in guiding treatment decisions.”

There are more than 200,000 MM and ALL patients living in the U.S., and
more than 35,000 new cases are diagnosed each year. The clonoSEQ Assay
uses NGS to precisely identify and monitor MRD in these patients
throughout treatment and remission, with greater sensitivity than other
technologies for any given amount of bone marrow sample.1
Detecting MRD with deep sensitivity can be clinically informative for
the many patients being treated for these cancers.

The FDA clearance of clonoSEQ is an important advance for patients with
MM and ALL and for the oncologists who care for them. This milestone
underscores the importance of MRD as a predictor of patient outcomes,”
said Aaron Logan, associate professor, Division of Hematology and Blood
and Marrow Transplant, UCSF. “Quantification of MRD should be standard
practice to assess response to treatment, monitor disease progression
and direct patient care. It is thus essential to have an MRD assay that
meets regulatory standards and can accurately and reliably measure and
track disease burden over time.”

For patients who achieve complete response to cancer treatment by
traditional response criteria, the presence or absence of MRD has been
demonstrated to have a significant relationship with patient outcomes.2
For this reason, many pharmaceutical companies have begun using MRD as a
clinically meaningful endpoint to evaluate efficacy and to guide use of
their therapies.

This year has been historic for the field of hematology, with a
paradigm-shifting FDA decision to approve the first therapy, BLINCYTO,
based on the MRD status of a patient with ALL, validating the clinical
relevance of MRD in ALL as a clinically meaningful endpoint,” said Greg
Friberg, M.D., vice president, Global Development, Oncology at Amgen.
Now, physicians and patients will have access to the first FDA-cleared
MRD assay, providing them with another important tool to make informed
decisions about treatments to help achieve MRD negativity. We look
forward to continuing our collaboration with Adaptive Biotechnologies to
further explore MRD and deliver on our mission to serve patients through
transformative science.”

The recent FDA review and approval of drugs with MRD included as a
clinical endpoint, as well as the agency’s inclusion of MRD on the
recently released list
of surrogate endpoints
that can serve as the basis of drug
approvals, demonstrate the clinical actionability of MRD and reinforce
the need for an accurate and standardized, FDA-cleared method like
clonoSEQ.3,4

The clearance of the clonoSEQ Assay is an exciting advance for MM and
ALL patients and physicians; as MRD is increasingly used to inform
treatment decisions, the importance of having an accurate and
standardized assessment method becomes paramount,” said Chad Robins,
chief executive officer and co-founder of Adaptive Biotechnologies. “NGS
MRD testing is already part of National Comprehensive Cancer Network
(NCCN) treatment guidelines for patients with MM, ALL, and CLL, and
clonoSEQ is already in use for patient management in the majority of
NCCN cancer centers, further demonstrating the clinical importance of
MRD and acceptance of NGS MRD testing by the oncology community.
Adaptive is working diligently with public and private payers to make
clonoSEQ broadly available to patients in need.”

About Minimal Residual Disease

Minimal residual disease (MRD), also referred to as measurable residual
disease, refers to cancer cells that remain in the body after treatment
for patients with lymphoid cancers. These cells can be present at levels
undetectable by traditional morphologic methods, microscopic examination
of blood, or a bone marrow or a lymph node biopsy.

MRD is used by physicians to detect and monitor disease burden in
patients and to inform their treatment decisions. Clinical practice
guidelines recommend assessing MRD at multiple time points during
treatment and maintenance in MM and ALL, and guidelines for both
diseases include NGS as a recommended testing method.5,6 The
prognostic value of MRD assessment has been demonstrated in multiple
lymphoid cancers.7,8 Controlled trials have shown that even
small amounts of disease are profoundly significant for predicting a
patient’s long-term clinical outcomes.1,9,10,11,12 Therefore,
highly sensitive, standardized molecular technologies are needed for
reliable detection of MRD.

Measurement of MRD is currently being evaluated as a way to measure
efficacy in drug trials, with the potential to expedite the approval of
emerging therapies.13

About the clonoSEQ® Assay

The Adaptive Biotechnologies clonoSEQ Assay has been granted De Novo
designation by the FDA as an in vitro diagnostic (IVD) to detect
and monitor minimal residual disease (MRD) in patients with multiple
myeloma (MM) and B-cell acute lymphoblastic leukemia (ALL) using DNA
from bone marrow samples. It identifies and quantifies specific DNA
sequences found in malignant cells, allowing clinicians to monitor
patients for changes in disease burden during and after treatment. This
robust assay provides sensitive and accurate measurement of residual
disease that allows physicians to predict patient outcomes, assess
response to therapy over time, monitor patients during remission and
detect potential relapse. The clonoSEQ Assay is a single-site assay
performed at Adaptive Biotechnologies. It is also available as a
CLIA-regulated laboratory developed test (LDT) service for use in other
lymphoid cancers.

clonoSEQ was reviewed under the FDA’s De Novo premarket review pathway,
a regulatory pathway for some low- to moderate-risk novel devices for
which there is no legally marketed predicate device.

For important information about the FDA-cleared uses of clonoSEQ,
including the full intended use, limitations, and detailed performance
characteristics, please visit www.clonoSEQ.com/technical-summary.

About Adaptive Biotechnologies

Adaptive Biotechnologies is the pioneer and leader in combining
next-generation sequencing (NGS) and expert bioinformatics to profile
T-cell and B-cell receptors. Adaptive is bringing the accuracy and
sensitivity of its immunosequencing platform to researchers and
clinicians around the world to drive groundbreaking research in cancer
and other immune-mediated diseases. Adaptive also translates
immunosequencing discoveries into clinical diagnostics and therapeutic
development to improve patient care. For more information, please visit adaptivebiotech.com.

Adaptive Biotechnologies does not endorse the use of any particular
therapy.

1 Perrot A, et al. Blood. 2018:blood-2018-06-858613.

2 Martinez-Lopez J, et al. Blood. 2014;123(20):3073-9.

3 BLINCYTO (blinatumomab) Full Prescribing Information.
Retrieved September 26, 2018 from: https://pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/blincyto/blincyto_pi_hcp_english.pdf

4 DARZALEX (daratumumab) Full Prescribing Information.
Retrieved September 26, 2018 from: http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf

5 NCCN Clinical Practice Guidelines in Oncology for Multiple
Myeloma. V.3.2018.

6 NCCN Clinical Practice Guidelines in Oncology: Acute
Lymphoblastic Leukemia. Version 1.2018.

7 Wu, D, et al. Clin Cancer Res. 201:20(17):4540-9.

8 Korde N, et al. JAMA Oncol. 2015:1(6):746-54.

9 Dimopoulos MA, et al. N Engl J Med.
2016;375:1319-1331.

10 Pulsipher M, et al. Blood. 2015;125(22):3501-8.
Adaptive Biotechnologies provided financial support for this study.

11 Mannis GN, et al. Biol Blood Marrow Transplant. 2016;22:1030-1036.
Adaptive Biotechnologies provided financial support for this study.

12 Logan AC, et al. Biol Blood Marrow Transplant. 2014;20(9):1307-13. Adaptive
Biotechnologies provided financial support for this study. Clinician has
received compensation to participate in advisory meetings sponsored by
Adaptive.

13 Avet-Loiseau H. Am Soc Clin Oncol Educ Book. 2016;
35e425-30.

Contacts

Adaptive Biotechnologies
Beth Keshishian, 917-912-7195
media@adaptivebiotech.com