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Sanofi : FDA approves Libtayo® (cemiplimab) as first and only treatment for advanced cutaneous squamous cell carcinoma

On September 28, 2018 The U.S. Food and Drug Administration (FDA) reported that it has approved Libtayo (cemiplimab-rwlc) for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation (Press release, Sanofi, SEP 28, 2018, View Source [SID1234529938]). Libtayo is a fully-human monoclonal antibody targeting the immune checkpoint receptor PD-1 (programmed cell death protein-1) and is the first and only treatment specifically approved and available for advanced CSCC in the U.S.

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"Today’s FDA decision is great news for patients with advanced CSCC, who previously had no approved treatment options. This is especially true because these patients are no longer candidates for curative surgery or radiation," said Michael R. Migden, M.D., a lead investigator in the pivotal CSCC clinical program and Professor in the Departments of Dermatology and Head and Neck Surgery at The University of Texas MD Anderson Cancer Center. "Libtayo is an important new immunotherapy option for U.S. physicians to help address a significant unmet need in this patient group."

CSCC is the second most common form of skin cancer and is responsible for an estimated 7,000 deaths each year in the U.S. It currently accounts for approximately 20 % of all skin cancers in the U.S., with the number of newly diagnosed cases expected to rise annually. When CSCC invades deeper layers of the skin or adjacent tissues, it is categorized as locally advanced. Once it spreads to other distant parts of the body, it is considered metastatic.

"By following the science, we identified early on that advanced CSCC was a promising target for investigation with Libtayo," said Israel Lowy, M.D., Ph.D., Vice President of Global Clinical Development and Head of Translational Science and Clinical Oncology, Regeneron. "We are proud to offer patients in the U.S. this first and only treatment for advanced CSCC and remain focused on advancing our clinical research investigating Libtayo as a potential monotherapy and combination therapy in other cancer types."

Libtayo was evaluated by the FDA under Priority Review, which is reserved for medicines that represent significant improvements in safety or efficacy in treating serious conditions, and in 2017 was granted Breakthrough Therapy Designation status for advanced CSCC. Breakthrough Therapy Designation was created to expedite the development and review of drugs that have the potential for substantial improvement in the treatment of serious or life-threatening conditions.

"In the U.S., CSCC accounts for one in five skin cancers, and the number of new diagnoses is increasing," said Olivier Brandicourt, M.D., Chief Executive Officer, Sanofi. "We believe Libtayo has the potential to make a difference for U.S. patients with advanced CSCC, as it helps to fill a critical gap in treatment options. We are committed to bringing this important medicine to patients in other countries around the world as quickly as possible."

The recommended dosage of Libtayo is 350 mg administered as an intravenous infusion over 30 minutes every three weeks, until disease progression or unacceptable toxicity. Libtayo is available as a single-dose 350 mg vial.

Libtayo is expected to provide significant value for patients with advanced CSCC and those who care for them. The U.S. list price, or wholesale acquisition cost, is $9,100 per three-week treatment cycle. Actual costs to patients are generally anticipated to be lower as the list price does not reflect insurance coverage, copay support, or financial assistance from patient support programs.

Sanofi and Regeneron are committed to helping U.S. patients who have been prescribed Libtayo access their medication. The companies have launched Libtayo Surround(TM) to help patients understand how Libtayo may be covered by their health insurance plans. Additionally, Libtayo Surround is designed to help eligible patients who need financial assistance with their prescription. For more information, please call 1-877-LIBTAYO (1-877-542-8296), Option 1, or visit www.Libtayo.com.

Sanofi Genzyme, the specialty care global business unit of Sanofi, and Regeneron will market Libtayo jointly in the U.S.

Pivotal advanced CSCC clinical program and results

The FDA approval of Libtayo was based on a combined analysis of data from an open-label, multi-center, non-randomized Phase 2 trial known as EMPOWER-CSCC-1 (Study 1540) and two advanced CSCC expansion cohorts from a multi-center, open-label, non-randomized Phase 1 trial (Study 1423). Together, the trials represent the largest prospective data set in advanced CSCC.

The major efficacy outcome measures for the integrated analysis of EMPOWER-CSCC-1 and the two CSCC expansion cohorts were confirmed objective response rate (ORR), as assessed by independent central review (ICR), and ICR-assessed duration of response (DOR). The efficacy analysis was conducted when all patients had the opportunity for at least six months of follow-up.

Combined efficacy results (n=108) from EMPOWER-CSCC-1 and the two advanced CSCC expansion cohorts from the Phase 1 trial were as follows:

Efficacy Endpoints* Metastatic
CSCC
(n = 75) Locally Advanced
CSCC
(n= 33) Combined
CSCC
(n = 108)
Confirmed ORR
ORR
(95% confidence interval [CI]) 47%
(35, 59) 49%
(31, 67) 47%
(38, 57)
Complete response rate** 5% 0% 4%
Partial response rate 41% 49% 44%
DOR
Range in months 3-15+ 1-13+ 1-15+
Patients with DOR >= 6 months, n (%) 21 (60%) 10 (63%) 31 (61%)
+Denotes ongoing at last assessment
*Median duration of follow-up: metastatic CSCC: 8.1 months; locally advanced CSCC: 10.2 months; combined CSCC: 8.9 months
**Only includes patients with complete healing of prior cutaneous involvement; locally advanced CSCC patients in EMPOWER-CSCC-1 required biopsy to confirm complete response.

For the combined safety analysis (n=163) of EMPOWER-CSCC-1 and the two advanced CSCC expansion cohorts, the most common adverse reactions reported were fatigue (29%), rash (25%) and diarrhea (22%). Libtayo was permanently discontinued due to adverse reactions in 5% of patients; adverse reactions resulting in permanent discontinuation were pneumonitis, autoimmune myocarditis, hepatitis, aseptic meningitis, complex regional pain syndrome, cough and muscular weakness. Serious adverse reactions (SAEs) occurred in 28% of patients. SAEs that occurred in at least 2% of patients were cellulitis, sepsis, pneumonia, pneumonitis and urinary tract infection.

Cemiplimab-rwlc development program overview

Cemiplimab-rwlc is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.

In April 2018, the European Medicines Agency (EMA) accepted for review the Marketing Authorization Application for Libtayo for the treatment of patients with metastatic CSCC or with locally advanced CSCC who are not candidates for surgery. The EMA review process is anticipated to be complete in the first half of 2019. There are currently no EMA-approved treatments for advanced CSCC. Regulatory applications in additional countries are also being considered for submission later in 2018.

In addition to advanced CSCC, cemiplimab-rwlc is being investigated in trials in non-small cell lung cancer, basal cell carcinoma, and cervical cancer along with trials in squamous cell carcinoma of the head and neck, melanoma, colorectal cancer, prostate cancer, multiple myeloma, Hodgkin lymphoma and non-Hodgkin lymphoma. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

What is the most important information I should know about Libtayo?
Libtayo is a medicine that may treat a type of skin cancer by working with your immune system. Libtayo can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any symptoms of the following problems or these symptoms get worse:

Lung problems (pneumonitis). Signs and symptoms of pneumonitis may include new or worsening cough, shortness of breath, and chest pain.
Intestinal problems (colitis) that can lead to tears or holes in your intestine. Signs and symptoms of colitis may include diarrhea (loose stools) or more frequent bowel movements than usual; stools that are black, tarry, or sticky or that have blood or mucus; and severe stomach-area (abdomen) pain or tenderness.
Liver problems (hepatitis). Signs and symptoms of hepatitis may include yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual.
Hormone gland problems (especially the adrenal glands, pituitary, thyroid and pancreas). Signs and symptoms that your hormone glands are not working properly may include headaches that will not go away or unusual headaches, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, feeling cold, constipation, deeper voice, very low blood pressure, urinating more often than usual, nausea or vomiting, stomach-area (abdomen) pain, and changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness.
Kidney problems, including nephritis and kidney failure. Signs of these problems may include decrease in your amount of urine, blood in your urine, swelling in your ankles, and loss of appetite.
Skin problems. Signs of these problems may include rash, itching, skin blistering, and painful sores or ulcers in the mouth, nose, throat, or genital area.
Problems in other organs. Signs of these problems may include headache, tiredness or weakness, sleepiness, changes in heartbeat (such as beating fast, seeming to skip a beat, or a pounding sensation), confusion, fever, muscle weakness, balance problems, nausea, vomiting, stiff neck, memory problems, seizures (encephalitis), swollen lymph nodes, rash or tender lumps on skin, cough, shortness of breath, vision changes, or eye pain (sarcoidosis), seeing or hearing things that are not there (hallucinations), severe muscle weakness, low red blood cells (anemia), bruises on the skin or bleeding, and changes in eyesight.
Rejection of a transplanted organ. Your doctor should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had.
Infusion (IV) reactions that can sometimes be severe and life-threatening. Signs of these problems may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, fever, feeling of passing out, back or neck pain, and facial swelling.

Getting medical treatment right away may help keep these problems from becoming more serious.

Your healthcare provider will check you for these problems during your treatment with Libtayo. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may delay or completely stop treatment if you have severe side effects.

Before you receive Libtayo, tell your healthcare provider about all your medical conditions, including if you:

Your healthcare provider will give you a pregnancy test before you start treatment.
You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of Libtayo. Talk with your healthcare provider about birth control methods that you can use during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Libtayo.
are breastfeeding or plan to breastfeed. It is not known if Libtayo passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of Libtayo.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Libtayo include tiredness, rash, and diarrhea. These are not all the possible side effects of Libtayo. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals and Sanofi at 1-877-542-8296.

Please see accompanying full Prescribing Information, including Medication Guide.

What is Libtayo?

Libtayo is a prescription medicine used to treat people with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.

It is not known if Libtayo is safe and effective in children.

Altimmune Announces Pricing of $12 Million Underwritten Public Offering

On September 28, 2018 Altimmune, Inc. (Nasdaq: ALT), a clinical-stage immunotherapeutics company, reported the pricing of an underwritten public offering of common units and pre-funded units for a combined total of 2,400,000 units (Press release, Altimmune, SEP 28, 2018, View Source [SID1234529901]). Each common unit is being sold at a public offering price of $5.00 and consists of a share of its common stock and a warrant to purchase one share of common stock at an exercise price of $6.00. Each warrant will be exercisable immediately and will expire five years from the date of issuance. Each pre-funded unit consists of a pre-funded warrant to purchase one share of our common stock at an exercise price of $0.01 per share and a warrant. The purchase price of each Pre-funded Unit is equal to the price per common unit being sold to the public in this offering, minus $0.01. The pre-funded warrants will be immediately exercisable and may be exercised at any time until all of the pre-funded warrants are exercised in full.

Roth Capital Partners is acting as sole manager for the offering.

Expected gross proceeds are expected to be approximately $12 million before the underwriting discount and offering expenses payable by Altimmune. In addition, Altimmune has granted the underwriters a 30-day overallotment option to purchase up to 15% of the securities issued in the offering.

The offering is expected to close on or about October 2, 2018, subject to customary closing conditions. Altimmune intends to use the net proceeds from this offering for the continued advancement of development activities for our clinical-stage product pipeline, general corporate purposes, strategic growth opportunities and repayment of our outstanding $1.5 million in aggregate principal amount of convertible notes.

The securities described above are being offered by Altimmune pursuant to a registration statement on Form S-1 (File No. 333-226441) that was declared effective by the Securities and Exchange Commission (SEC) on September 27, 2018. A final prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s web site at www.sec.gov. Copies of the final prospectus relating to this offering may be obtained, when available, by contacting Roth Capital Partners, LLC, Attention: Equity Capital Markets, 888 San Clemente Drive, Suite 400, Newport Beach, California 92660, by telephone at (800) 678-9147 or e-mail at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

TRILLIUM THERAPEUTICS TO PROVIDE UPDATE ON TTI-621 CLINICAL
PROGRAMS AT TWO SCIENTIFIC CONFERENCES

On September 28, 2018 Trillium Therapeutics Inc. (NASDAQ/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported that it will be providing updates on its two clinical trials with TTI-621, a dual function SIRPaFc IgG1 decoy receptor that targets CD47, at two upcoming scientific conferences (Press release, Trillium Therapeutics, SEP 28, 2018, View Source [SID1234529681]). As previously announced, the presentations will be made on September 28 at the European Organisation for Research and Treatment of Cancer, Cutaneous Lymphoma Task Force (EORTC CLTF) meeting in St. Gallen, Switzerland and the 16th Annual Discovery on Target conference in Boston, MA. The presentations will be available on the Company’s website after the presentations have been delivered.

The presentation at the EORTC CLTF meeting will provide an update on the safety and efficacy of the ongoing multicenter, open-label phase 1 intratumoral trial of TTI-621 in 23 patients with relapsed/refractory mycosis fungoides/Sézary syndrome, 20 of whom only received induction therapy consisting of 1-6 injections over 2 weeks. Local delivery of TTI-621 was well tolerated, with no treatment-related > Grade 3 adverse events or dose-limiting toxicity observed. Reductions in CAILS scores, which measure local lesion responses, were observed in 89% of patients, with 42% exhibiting reductions of 50% or greater. These responses occurred rapidly within the 2- week induction period. Similar

CAILS scores changes were seen in adjacent non-injected lesions, suggesting locoregional effects that were not confined to the site of injection. Evidence of a systemic (abscopal) effect was observed in 1 of 2 patients receiving continuation monotherapy beyond the 2-week induction therapy. In addition, data suggest a combination effect with pegylated IFN-alpha-2a.

"These data expand on the observations first presented at ASH (Free ASH Whitepaper) 2017, and highlight the potential value of localized delivery of TTI-621 in heavily pre-treated mycosis fungoides/ Sézary syndrome patients," said Dr. Yaping Shou, Trillium’s Chief Medical Officer. "We are particularly encouraged to see reductions in CAILS scores after such a short course of therapy, and the abscopal effect seen in one of the two patients receiving continuation treatment suggest that a longer duration of dosing may offer further opportunity to induce systemic responses."

"The ability to induce rapid anti-tumor responses through local administration with our potent IgG1-containing Fc fusion protein opens up numerous possibilities, not only in mycosis fungoides but also in many solid tumors. As is the case with other agents targeting the innate immune system, such as STING and TLR agonists, local administration is the route of choice to ensure instant high local drug concentrations at the site of the tumor," said Dr. Niclas Stiernholm, Trillium’s President and Chief Executive Officer. "We intend to expand the intratumoral program both with respect to additional indications and combination therapies with complementary immunostimulatory therapies, especially those acting downstream of CD47."

The presentation at the Discovery on Target conference will provide a high level update of the safety and efficacy of the ongoing multicenter, open-label phase 1a/b intravenous trial of TTI-621 in patients with relapsed/refractory hematologic malignancies. Based on an expanded data set of 163 patients, weekly infusions of TTI-621 were shown to be well tolerated. Thrombocytopenia was the most frequent grade 3 or higher treatment-emergent adverse event, occurring in 20% of patients. Platelet reductions, however, were shown to be transient and pre-dose platelet levels remained steady during the course of the study. Notably, the reversible thrombocytopenia did not lead to an increased risk of bleeding and had no impact on drug delivery, nor was there a significant impact of TTI-621 on hemoglobin levels. Monotherapy efficacy was observed in patients with mycosis fungoides (19% ORR, n=21), peripheral T-cell lymphoma, or PTCL (25% ORR, n=12), and diffuse large B-cell lymphoma, or DLBCL (25% ORR, n=8), and in DLBCL patients when combined with rituximab (25% ORR, n=24). This clinical activity was observed in patients receiving relatively low doses of drug (0.2 mg/kg for monotherapy or 0.1 mg/kg in combination with rituximab). Dose intensification beyond 0.2 mg/kg is currently ongoing, and doses of 0.5 mg/kg have been well tolerated for up to 27 weeks.

"These data reinforce our prior observations that thrombocytopenia, which we believe to be an on-target pharmacodynamic effect, does not appear to be clinically consequential. Based on the data in hand, the transient decrease in platelets is not associated with bleeding events or premature treatment discontinuations, and has not impacted our ability to dose intensify patients beyond 0.2 mg/kg," commented Dr. Shou. "The monotherapy

anti-tumor activity we have observed in multiple disease indications is particularly intriguing given that patients have received relatively low doses of drug. Characterizing the efficacy of TTI-621 at higher doses, which is currently ongoing, remains a top priority in the intravenous trial."

"Having concluded this exploratory phase in a wide variety of hematologic malignancies and having gained increased clarity with respect to potential registration paths, we plan to move forward with three distinct clinical programs: intratumoral mono- and combination-therapy in CTCL, intravenous monotherapy in both CTCL and PTCL, as well as intravenous combination therapy in DLBCL," said Dr. Stiernholm. "While we are gratified to have observed meaningful clinical responses with monotherapy at low doses, we are equally excited about how well tolerated TTI-621 appears to be, allowing us to incorporate dose intensification as a major component of our clinical efforts moving forward."

FDA Approves Libtayo® (cemiplimab-rwlc) as First and Only Treatment for Advanced Cutaneous Squamous Cell Carcinoma

On September 28, 2018 Regeneron Pharmaceuticals, Inc. (NASDAQ : REGN) and Sanofi reported that the U.S. Food and Drug Administration (FDA) has approved Libtayo (cemiplimab-rwlc) for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation (Press release, Regeneron, SEP 28, 2018, View Source [SID1234529652]). Libtayo is a fully-human monoclonal antibody targeting the immune checkpoint receptor PD-1 (programmed cell death protein-1) and is the first and only treatment specifically approved and available for advanced CSCC in the U.S.

CSCC is the second most common form of skin cancer and is responsible for an estimated 7,000 deaths each year in the U.S. It currently accounts for approximately 20% of all skin cancers in the U.S., with the number of newly diagnosed cases expected to rise annually. When CSCC invades deeper layers of the skin or adjacent tissues, it is categorized as locally advanced. Once it spreads to other distant parts of the body, it is considered metastatic.

Libtayo is expected to provide significant value for patients with advanced CSCC and those who care for them. The U.S. list price, or wholesale acquisition cost, is $9,100 per three-week treatment cycle. Actual costs to patients are generally anticipated to be lower as the list price does not reflect insurance coverage, copay support or financial assistance from patient support programs.

Regeneron and Sanofi are committed to helping U.S. patients who have been prescribed Libtayo access their medication. The companies have launched Libtayo Surround to help patients understand how Libtayo may be covered by their health insurance plans. Additionally, Libtayo Surround is designed to help eligible patients who need financial assistance with their prescription. For more information, please call 1-877-LIBTAYO (1-877-542-8296), Option 1, or visit www.Libtayo.com.

Regeneron and Sanofi Genzyme, the specialty care global business unit of Sanofi, will market Libtayo jointly in the U.S. Libtayo was invented by Regeneron using the company’s proprietary VelocImmune technology that yields optimized fully-human antibodies.

Pivotal Advanced CSCC Clinical Program and Results
The FDA approval of Libtayo was based on a combined analysis of data from an open-label, multi-center, non-randomized Phase 2 trial known as EMPOWER-CSCC-1 (Study 1540) and two advanced CSCC expansion cohorts from a multi-center, open-label, non-randomized Phase 1 trial (Study 1423). Together, the trials represent the largest prospective data set in advanced CSCC.

Combined efficacy results (n=108) from EMPOWER-CSCC-1 and the two advanced CSCC expansion cohorts from the Phase 1 trial were as follows:

Efficacy Endpoints*

Metastatic

CSCC

(n = 75)

Locally Advanced

CSCC

(n= 33)

Combined

CSCC

(n = 108)

Confirmed ORR

ORR
(95% confidence interval [CI])

47%

(35, 59)

49%

(31, 67)

47%

(38, 57)

Complete response rate†

Partial response rate

41%

49%

44%

DOR

Range in months

3-15+

1-13+

1-15+

Patients with DOR ≥ 6 months, n (%)

21 (60%)

10 (63%)

31 (61%)

+Denotes ongoing at last assessment
*Median duration of follow-up: metastatic CSCC: 8.1 months; locally advanced CSCC: 10.2 months; combined CSCC: 8.9 months
†Only includes patients with complete healing of prior cutaneous involvement; locally advanced CSCC patients in EMPOWER-CSCC-1 required biopsy to confirm complete response.

Cemiplimab-rwlc Development Program Overview
Cemiplimab-rwlc is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

What is the most important information I should know about Libtayo?

Libtayo is a medicine that may treat a type of skin cancer by working with your immune system. Libtayo can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any symptoms of the following problems or these symptoms get worse:

Before you receive Libtayo, tell your healthcare provider about all your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus;
have had an organ transplant;
have lung or breathing problems;
have liver or kidney problems;
have diabetes;
are pregnant or plan to become pregnant; Libtayo can harm your unborn babyFemales who are able to become pregnant:
Your healthcare provider will give you a pregnancy test before you start treatment.
You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of Libtayo. Talk with your healthcare provider about birth control methods that you can use during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Libtayo.
are breastfeeding or plan to breastfeed. It is not known if Libtayo passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of Libtayo.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Please see accompanying full Prescribing Information, including Medication Guide.

What is Libtayo?

Libtayo is a prescription medicine used to treat people with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.

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

On September 28, 2018 Adaptive Biotechnologies reported 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 (Press release, Adaptive Biotechnologies, SEP 28, 2018, View Source [SID1234529651]). 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.