On September 11, 2023 Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), a clinical-stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors, reported that it intends to offer and sell, subject to market and other conditions, $250.0 million of shares of its common stock in an underwritten public offering (Press release, Crinetics Pharmaceuticals, SEP 11, 2023, View Source [SID1234635061]). In addition, Crinetics intends to grant the underwriters a 30-day option to purchase up to an additional $37.5 million of shares of common stock. All of the shares to be sold in the offering are to be sold by Crinetics. There can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Crinetics intends to use the net proceeds from the proposed offering to fund the development of paltusotine, CRN04894 and its other research and development programs, and for working capital and general corporate purposes.

J.P. Morgan, Morgan Stanley, Leerink Partners and Piper Sandler are acting as joint book-running managers for the offering.

The securities described above are being offered by Crinetics pursuant to a shelf registration statement that became automatically effective upon its filing with the Securities and Exchange Commission (SEC). A preliminary prospectus supplement and accompanying prospectus relating to this offering will be filed with the SEC. When available, copies of the preliminary prospectus supplement and the accompanying prospectus relating to this offering may be obtained from: J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (866) 803-9204 or by email at [email protected]; Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, NY 10014 or by email at [email protected]; Leerink Partners LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, by telephone at (800) 808-7525, ext. 6105, or by email at [email protected]; or Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by telephone at (800) 747-3924 or by email at [email protected]. Electronic copies of the preliminary prospectus supplement and accompanying prospectus will also be available on the website of the SEC at www.sec.gov.

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

On September 11, 2023 Avalo therapeutics presented its corporate presentation (Presentation, Avalo Therapeutics, SEP 11, 2023, View Source [SID1234635060]).

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On September 11, 2023 Bristol Myers Squibb (NYSE: BMY) reported six-year results from Part 1 of the Phase 3 CheckMate -227 trial, which continues to demonstrate long-term, durable survival benefits of Opdivo (nivolumab)plus Yervoy (ipilimumab)compared to chemotherapy in the first-line treatment of patients with metastatic non-small cell lung cancer (mNSCLC), regardless of PD-L1 expression levels (Press release, Bristol-Myers Squibb, SEP 11, 2023, View Source;227-Trial-Show-Durable-Long-Term-Survival-with-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-in-the-First-Line-Treatment-of-Patients-with-Metastatic-Non-Small-Cell-Lung-Cancer/default.aspx [SID1234635059]). Follow-up results will be featured in an oral presentation (Abstract #OA14.03) and have been selected for the official press program at the IASLC 2023 World Conference on Lung Cancer (#WCLC23) hosted by the International Association for the Study of Lung Cancer on September 11, 2023, from 2:32 a.m. to 2:42 a.m. EDT / 2:32 p.m. to 2:42 p.m. SGT.

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With a minimum follow-up of over six years (73.5 months), the longest reported for a Phase 3 trial with immunotherapy in mNSCLC:

Follow-up results of the primary endpoint population of patients with tumor PD-L1 expression ≥1% show that the six-year survival rate for Opdivo plus Yervoy was 22%, compared to 13% for chemotherapy (Hazard Ratio [HR] 0.78; 95% Confidence Interval [CI]: 0.67 to 0.91).
In an exploratory analysis of patients with PD-L1 expression <1%, more than three times as many patients treated with Opdivo plus Yervoy were alive at six years compared to those treated with chemotherapy (16% vs. 5%, respectively; HR 0.65; 95% CI: 0.52 to 0.81).
Among those who responded to treatment, greater proportions of patients had tumor burden reduction ≥80% with Opdivo plus Yervoy vs. chemotherapy in both the PD-L1 ≥1% (15% vs. 3%, respectively) and <1% (8% vs. 1%, respectively) subgroups, and six-year overall survival (OS) rates for patients with tumor burden reduction ≥80% with Opdivo plus Yervoy were higher compared to chemotherapy (59% vs. 42% for PD-L1 ≥1% and 77% vs. 0% for PD-L1 <1%, respectively).
The safety profile for the dual immunotherapy combination Opdivo plus Yervoy remained consistent with previously reported data from this trial and was manageable with established protocols, with no new safety signals identified.
"Immunotherapy has transformed the treatment of advanced lung cancer, and thankfully, a diagnosis no longer means the same thing as it used to for many patients. With these six-year results, we are seeing remarkably sustained and durable clinical survival benefits with nivolumab plus ipilimumab year-over-year," said Solange Peters, M.D., Ph.D., professor and chair of medical oncology and the thoracic malignancies program in the Department of Oncology at the University Hospital of Lausanne in Lausanne, Switzerland. "The long-term efficacy seen with the dual immunotherapy regimen in CheckMate -227 reinforce the importance of nivolumab plus ipilimumab to transform outcomes for appropriate patients with metastatic non-small cell lung cancer."

"We are ecstatic to see Opdivo plus Yervoy continue to demonstrate almost double the overall survival rates as chemotherapy after six years of follow-up – the longest-ever for a Phase 3 trial with immunotherapy in metastatic non-small cell lung cancer. Further, the Opdivo plus Yervoy regimen more than tripled survival for patients with PD-L1 expression <1%, a population that is difficult to treat and faces high unmet needs," said Abderrahim Oukessou, M.D., vice president, thoracic cancers global program lead, Bristol Myers Squibb. "Our results presented at WCLC 2023 build on our legacy of transforming survival expectations with immunotherapy combinations. Looking ahead, we are excited to expand our research into targeted and small molecule therapies, as well as additional immunotherapy combinations, in the hope of potentially finding solutions for as many people living with thoracic cancers as possible."

Opdivo plus Yervoy-based combinations have shown significant improvements in OS in six Phase 3 clinical trials in five tumors to date: metastatic NSCLC, metastatic melanoma, advanced renal cell carcinoma, malignant pleural mesothelioma and esophageal squamous cell carcinoma.

About CheckMate -227

CheckMate -227 is a multi-part open-label global randomized Phase 3 trial evaluating Opdivo-based regimens versus platinum-doublet chemotherapy in patients with first-line metastatic non-small cell lung cancer (NSCLC) across non-squamous and squamous tumor histologies.

There are two independent primary endpoints in Part 1 for Opdivo plus Yervoy (versus chemotherapy): overall survival (OS) in patients whose tumors express PD-L1 (assessed in patients enrolled in Part 1a) and progression-free survival (PFS) in patients with tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb) across the PD-L1 spectrum (assessed in patients enrolled across Parts 1a and 1b). Patients were treated as follows:

Part 1a: Opdivo (3 mg/kg every 2 weeks) plus Yervoy (1 mg/kg every 6 weeks), Opdivo monotherapy (240 mg every 2 weeks), or chemotherapy (every 3 weeks for up to four cycles) in patients whose tumors express PD-L1 (≥1%)
Part 1b: Opdivo plus Yervoy,Opdivo (360 mg every 3 weeks) plus chemotherapy (every 3 weeks for up to four cycles), or chemotherapy (every 3 weeks for up to four cycles) in patients whose tumors do not express PD-L1 (<1%)
Part 1 met both its independent primary endpoints of PFS with the Opdivo plus Yervoy combination versus chemotherapy in patients whose tumors have high (≥10 mut/Mb) TMB, regardless of PD-L1 expression, and OS demonstrating a superior benefit for Opdivo plus Yervoy versus chemotherapy in first-line metastatic NSCLC patients whose tumors expressed PD-L1 ≥1%.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. Survival rates vary depending on the stage and type of the cancer when diagnosed.

On September 11, 2023 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage precision oncology company developing therapies that target families of oncogenic mutations in patients with genetically defined cancers, reported the first patients dosed in mutation matched expansion cohorts of non-small cell lung cancer (NSCLC) in the ongoing Phase 1 clinical study evaluating BDTX-1535 (Press release, Black Diamond Therapeutics, SEP 11, 2023, View Source [SID1234635058]).

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BDTX-1535, a fourth-generation, brain-penetrant epidermal growth factor receptor (EGFR) MasterKey tyrosine kinase inhibitor (TKI), is under investigation for the treatment of NSCLC harboring intrinsic driver and/or acquired resistance (post-osimertinib) EGFR mutations and glioblastoma multiforme (GBM) with multiple EGFR alterations. The BDTX-1535 expansion cohort portion of the study will assess single-agent objective response rate (ORR) in a second- or third-line setting in NSCLC patients with EGFR intrinsic driver and/or acquired resistance mutations, who have received prior treatment with approved EGFR TKI.

The dosing of the first patients in the expansion cohorts follows the Company’s initial data readout from the dose escalation portion of the BDTX-1535 Phase 1 clinical study, which demonstrated clinical proof of activity through radiographic responses in NSCLC patients harboring diverse types of EGFR mutations including intrinsic driver and post-osimertinib acquired resistance EGFR mutations.

"The Phase 1 expansion cohorts will assess objective response rate and durability of response in NSCLC patients whose disease has progressed after prior EGFR inhibitor therapy, including prior osimertinib, and who have evidence of a variety of EGFR driver or resistance mutations that are targeted by BDTX-1535," said Sergey Yurasov, M.D., Ph.D., Chief Medical Officer of Black Diamond Therapeutics. "In conjunction with establishing an optimal dose for a future pivotal study, these efficacy data will be essential for establishing a regulatory pathway for BDTX-1535. Despite significant recent advances in treating lung cancer, there is a large unmet medical need for a targeted therapy for these EGFR mutation-positive NSCLC patients, for whom chemotherapy is still the most common treatment option."

"Dosing of the first patients in the BDTX-1535 dose expansion cohorts represents an important step towards offering an oral therapeutic with manageable side effects as a potential alternative to chemotherapy-based regimens following progression on osimertinib for patients with treatment-resistant lung cancer," said David Epstein, Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. "The population of EGFR mutation-positive NSCLC is genetically heterogeneous – which has presented challenges in the development of effective therapies. BDTX-1535 was designed to disrupt the limited existing treatment paradigm by addressing real-world patterns of patient-specific EGFR mutations, and we remain focused on the rapid advancement of this novel MasterKey inhibitor."

The discovery and development of BDTX-1535 was informed by the Company’s powerful Mutation-Allostery-Pharmacology (MAP) drug discovery engine, which leverages critical genomic profiling to expand the addressable patient population by targeting families of mutations with a single drug. Emergence of intrinsic driver and acquired resistance EGFR mutations to osimertinib represents a significant unmet need for patients with EGFR-mutant lung cancer. Thirteen percent of patients in the U.S. with EGFR mutation-positive NSCLC show presence of intrinsic driver mutations, which are associated with worse clinical outcomes when treated with currently approved EGFR TKIs. Fifteen percent of patients in the U.S. whose disease has progressed after osimertinib therapy show evidence of acquired resistance EGFR mutations (e.g., C797S) for which currently there is no approved EGFR TKI.

The Company is advancing BDTX-1535 as a potential targeted therapy option for patients with this broad spectrum of EGFR mutations in second-line NSCLC, and plans to investigate safety and efficacy in a first-line setting in NSCLC patients with intrinsic driver EGFR mutations after discussion with the U.S. Food and Drug Administration (FDA).

BDTX-1535 Phase 1 Clinical Study Design
The Phase 1 first-in-human, open-label clinical trial of BDTX-1535 (NCT05256290) consists of a dose escalation portion that evaluated the safety, pharmacokinetics (PK), and preliminary anti-tumor activity of BDTX-1535 followed by dose expansion cohorts. The trial is evaluating BDTX-1535 in patients with advanced/metastatic NSCLC harboring EGFR mutations with or without central nervous system (CNS) disease, or with recurrent GBM expressing EGFR alterations. The Phase 1 dose escalation portion of the study in NSCLC and GBM patients has been completed and the study is now progressing to evaluate BDTX-1535 as a single agent, second-line or third-line therapy in two cohorts of EGFR mutation-positive NSCLC patients with progressive disease after prior therapy with EGFR TKI (e.g., osimertinib) to assess ORR, CNS ORR, duration of response, and progression-free survival and further evaluate safety, tolerability and PK:

Second- or third-line NSCLC patients with acquired EGFR resistance mutations +/- CNS metastasis; and
Second- or third-line NSCLC patients with EGFR intrinsic driver mutations +/- CNS metastasis.

On September 11, 2023 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a commercial stage biopharmaceutical company focused on certain cancers and rare diseases, reported that the U.S. Food and Drug Administration (FDA) has approved APHEXDA (motixafortide) in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma (Press release, BioLineRx, SEP 11, 2023, View Source [SID1234635057]). APHEXDA is administered by injection, for subcutaneous use.

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Multiple myeloma is the second most-common hematologic malignancy. Autologous stem cell transplantation (ASCT) is part of the standard of care treatment paradigm for multiple myeloma and delivers prolonged survival for patients with this cancer type.1 The success of ASCT depends on adequate mobilization of stem cells during the treatment process. The American Society for Transplantation and Cellular Therapy (ASTCT) guidelines recommend a collection target of 3-5 x 106 CD34+ cells/kg.2 Additionally, collection of a sufficient number of stem cells to perform two transplantations is recommended.2-5 Historically, depending on induction regimens and mobilization strategies, up to 47% of patients have had challenges collecting target numbers of hematopoietic stem cells for ASCT after one apheresis session.6-7

"Greater numbers of patients with multiple myeloma are candidates for autologous stem cell therapy; however, achieving target collection goals can be difficult in some patients given modern barriers, including the treatment of older patients and use of contemporary induction regimens," said John DiPersio, MD, PhD, primary investigator for the GENESIS trial and

Professor of Medicine, Pathology and Immunology and Director of the Center for Gene and Cellular Immunotherapy at Washington University School of Medicine in St. Louis. "Innovation in this area of medicine has been needed, and today’s approval of APHEXDA addresses the demand for new therapies that can meet today’s challenges by delivering more reliability in stem cell mobilization, versus filgrastim alone, with fewer days of apheresis sessions and fewer doses of filgrastim for people living with this cancer."

The FDA approval of APHEXDA is based on results from the 2-part, Phase 3 GENESIS trial, a randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of APHEXDA (motixafortide) plus filgrastim, compared to placebo plus filgrastim, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Part 1 was a single center, lead-in, open-label study involving 12 patients treated with motixafortide plus filgrastim designed to ascertain the dose. Part 2 involved 122 patients who were randomized 2:1 in a double-blind, placebo-controlled, multicenter study.8

The assessment of CD34+ cells was performed by central and local laboratories. Central laboratory assessments were used for the efficacy results. Local laboratory results were used for clinical treatment decisions. APHEXDA plus filgrastim enabled 67.5% of patients to achieve the stem cell collection goal of ≥ 6 × 106 CD34+ cells/kg within two apheresis sessions, versus 9.5% for the placebo plus filgrastim regimen, as measured by central laboratory.9 Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the APHEXDA arm and 21.4% in the placebo arm, as measured by local laboratories.9 Local laboratory data were used for a sensitivity analysis. The data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted.

In GENESIS, the safety was evaluated in 92 patients with multiple myeloma who received APHEXDA 1.25 mg/kg subcutaneously plus filgrastim, and 42 patients who received placebo plus filgrastim. Serious adverse reactions occurred in 5.4% of patients receiving APHEXDA plus filgrastim. These reactions included vomiting, injection site reaction, hypersensitivity reaction, injection site cellulitis, hypokalemia and hypoxia. The most common adverse reactions occurring in GENESIS (incidence >20%) were injection site reactions (pain, erythema and pruritus), pruritus, flushing, and back pain.9

"Given the strong efficacy data shown in the GENESIS trial, which included patients who are representative of the current multiple myeloma patient population, we believe APHEXDA will play a critical role in addressing unmet needs and introduce a new treatment paradigm for this challenging cancer," said Philip Serlin, Chief Executive Officer of BioLineRx Ltd. "The company is working relentlessly to make this important innovation in stem cell mobilization available to appropriate patients, their physicians and transplant teams."

"FDA approval of APHEXDA, the company’s first approved therapeutic, is a tremendously exciting and important moment in our history and validates our drug development programs," said Ella Sorani, PhD, Chief Development Officer of BioLineRx Ltd. "We would like to thank all of the patients and families who have contributed to the research and development of APHEXDA."

Increased age, as well as exposure to lenalidomide-containing induction regimens, including 3-4 drug combination regimens, have been associated with impaired stem cell mobilization.2-3 The GENESIS study included patients considered representative of the typical multiple myeloma population undergoing ASCT, with a median age of 63 years and with ~70% of patients in both arms of the trial receiving lenalidomide-containing induction therapy.8 In this contemporary population, patients in the APHEXDA plus filgrastim arm were able to mobilize more than four times the amount of stem cells with a single dose over a 24-hour period compared with placebo plus filgrastim.8

BioLineRx expects to make APHEXDA available later this month. For further information about APHEXDA, please see the Important Safety Information below and the full Prescribing Information, and visit www.APHEXDA.com.

APHEXDA Investor Conference Call
The Company will host an investor conference call on September 12, 2023 at 8:00 a.m. EDT featuring remarks by Philip Serlin, Chief Executive Officer.

To access the conference call, please dial +1-888-281-1167 from the U.S. or +972-3-918-0685 internationally. A live webcast and a replay of the call can be accessed through the event page on the Company’s website. Please allow extra time prior to the call to visit the site and download any necessary software to listen to the live broadcast. The call replay will be available approximately two hours after completion of the live conference call. A dial-in replay of the call will be available until September 14, 2023; please dial +1-888-295-2634 from the US or +972-3-925-5904 internationally.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects some white blood cells called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells in the bone marrow. According to the American Cancer Society, in 2023, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma, and nearly 13,000 people will die from the disease in the U.S.10 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems, or infections.

About Autologous Stem Cell Transplantation
Autologous stem cell transplantation (ASCT) is part of the standard treatment paradigm for a number of blood cancers, including multiple myeloma. In the U.S., as many as 8,000 ASCTs are performed each year in patients with multiple myeloma.11 The current ASCT standard of care includes 4-6 cycles of induction therapy (an initial drug-combination regimen to position the patient for as deep a treatment response as possible). To begin the stem cell mobilization process, a patient will receive a daily dose of filgrastim (G-CSF) for four days. Daily doses of filgrastim will continue until the target collection goal is met with the addition of up to four daily doses of plerixafor as needed.12 For patients unable to mobilize sufficient numbers of cells for harvesting during this primary mobilization phase, rescue therapy may be carried out followed by an additional number of apheresis sessions as necessary.2

About the GENESIS Trial
GENESIS (NCT 03246529) is a 2-part, Phase-3, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of APHEXDA (motixafortide) plus filgrastim (G-CSF), compared to placebo plus filgrastim, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Part 1 was a single center, lead-in, open-label study involving 12 patients treated with motixafortide plus filgrastim designed to ascertain the dose. Part 2 involved 122 patients who were randomized 2:1 in a double-blind, placebo-controlled, multicenter study.8

The primary objective of the study was to evaluate if one dose of motixafortide plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in up to two apheresis sessions. A key secondary objective of the study was to evaluate if one dose of motixafortide plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in one apheresis session.8

The study met the primary endpoint with a high degree of statistical significance (p<0.0001). The assessment of CD34+ cells was performed by central and local laboratories. Central laboratory assessments were used for the efficacy results. Local laboratory results were used for clinical treatment decisions. APHEXDA plus filgrastim enabled 67.5% of patients to achieve the cell collection goal of ≥ 6 × 106 CD34+ cells/kg in up to two apheresis sessions with a single administration, versus 9.5% for the placebo plus filgrastim regimen, as measured by central laboratory.9 Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the APHEXDA arm and 21.4% in the placebo arm, as measured by local laboratories.13 Local laboratory data were used for a sensitivity analysis. The data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted.

The safety of APHEXDA was evaluated in 92 patients with multiple myeloma who received APHEXDA 1.25 mg/kg subcutaneously plus filgrastim and 42 patients who received placebo plus filgrastim for mobilization of hematopoietic stem cells for collection and apheresis. Serious adverse reactions occurred in 5.4% of patients receiving APHEXDA plus filgrastim. Serious adverse reactions included vomiting, injection site reaction, hypersensitivity reaction, injection site cellulitis, hypokalemia and hypoxia. The most common adverse reactions occurring in GENESIS (incidence >20%) were injection site reactions (pain, erythema, and pruritus), pruritus, flushing and back pain.9

Please see important safety information below.

About APHEXDA
APHEXDA (motixafortide) is a CXCR4 antagonist with long receptor occupancy (greater than 72 hours) that, in combination with filgrastim (G-CSF), enables mobilization of hematopoietic stem cells to the peripheral blood for collection and subsequent autologous stem cell transplantation in patients with multiple myeloma.9

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION
APHEXDA is indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
APHEXDA is contraindicated in patients with a history of serious hypersensitivity reactions to motixafortide.

WARNINGS AND PRECAUTIONS

Anaphylactic Shock and Hypersensitivity Reactions: Anaphylactic shock and hypersensitivity reactions have occurred. Premedicate all patients with a triple drug premedication regimen that includes an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor approximately 30-60 minutes prior to each dose of APHEXDA. Administer APHEXDA in a setting where personnel and therapies are immediately available for treatment of anaphylaxis and other systemic reactions. Monitor patients for 1 hour following APHEXDA administration and manage reactions promptly. Patients receiving negative chronotropic drugs (e.g., beta-blockers) may be more at risk for hypotension in the event of a hypersensitivity reaction and these drugs, when appropriate, should be replaced with non-chronotropic drugs.
Injection Site Reactions: Injection site reactions (73%) including pain (53%), erythema (27%), and pruritus (24%) have occurred. Severe reactions occurred in 9% of patients. Premedicate with an analgesic premedication (e.g., acetaminophen) prior to each APHEXDA dose. Use analgesic medication and local treatments post-dose, as needed.
Tumor Cell Mobilization in Patients with Leukemia: For the purpose of hematopoietic stem cell (HSC) mobilization, APHEXDA may cause mobilization of leukemic cells and subsequent contamination of the apheresis product. Therefore, APHEXDA is not intended for HSC mobilization and harvest in patients with leukemia.
Leukocytosis: Administering APHEXDA in conjunction with filgrastim increases circulating leukocytes as well as HSC populations. Monitor white blood cell counts during APHEXDA use.
Potential for Tumor Cell Mobilization: When APHEXDA is used in combination with filgrastim for HSC mobilization, tumor cells may be released from the marrow and subsequently collected in the leukapheresis product. The effect of potential reinfusion of tumor cells has not been well-studied.
Embryo-fetal Toxicity: Based on its mechanism of action, APHEXDA can cause fetal harm. Advise pregnant women of the potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating treatment with APHEXDA and advise use of effective contraception during treatment and for 8 days after the final dose.
ADVERSE REACTIONS
The most common adverse reactions (incidence >20%) in patients treated with APHEXDA were injection site reactions [73%, including pain (53%), erythema (27%), pruritus (24%)]; pruritus (38%); flushing (33%); back pain (21%).

USE IN SPECIFIC POPULATIONS

Pregnancy: Please see the important information in Warnings and Precautions under Embryo-fetal Toxicity.

Lactation: There are no data on the presence of motixafortide in human milk, the effects on the breastfed child, or the effects on milk production. Advise females that breastfeeding is not recommended during treatment with APHEXDA and for 8 days after the final dose.

Pediatric Use: The safety and effectiveness of APHEXDA have not been established in pediatric patients.

Please see the accompanying full Prescribing Information.