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Disease-Free Survival Data from CAPTIVATE Study Demonstrate Benefit of IMBRUVICA® (ibrutinib)-Based Regimen as Fixed Duration, First-Line Treatment for Patients with Chronic Lymphocytic Leukaemia

On December 4, 2020 Johnson & Johnson reported that New data from the Phase 2 CAPTIVATE study (PCYC-1142) were presented today during an oral session at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Abstract #123) (Press release, Johnson & Johnson, DEC 4, 2020, View Source;Based-Regimen-as-Fixed-Duration-First-Line-Treatment-for-Patients-with-Chronic-Lymphocytic-Leukaemia [SID1234572247]).1 The study evaluated the efficacy and safety of IMBRUVICA (ibrutinib) plus venetoclax in the treatment of adult patients with chronic lymphocytic leukaemia (CLL) and showed that, after achieving undetectable minimal residual disease (uMRD) in both the blood and bone marrow with the ibrutinib combination regimen, the one-year disease-free survival (DFS) of patients randomised to discontinue active treatment was comparable to that of patients randomised to continue ibrutinib monotherapy (95.3 percent vs. 100 percent, respectively [p=0.1475]).1

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"These data demonstrate the potential of this oral, once-daily, chemotherapy-free combination regimen in first-line treatment of CLL," said William Wierda,* M.D., Professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center and principal study investigator. "Once-daily treatment with ibrutinib remains the established standard of care in CLL; the latest results from the CAPTIVATE study underscore that the mechanistic synergy of ibrutinib and venetoclax delivers deep MRD remissions in the blood and bone marrow and enables treatment-free periods for patients."

The CAPTIVATE trial is evaluating adult patients younger than 70 years, including patients with high-risk disease, in two cohorts: an MRD Guided Cohort where treatment duration is guided by the patient’s MRD status after 12 cycles of combination ibrutinib plus venetoclax therapy; and a Fixed Duration Cohort where all patients stop therapy after 12 cycles of the combination, regardless of MRD status. Patients in the MRD Guided Cohort (n=164; median age, 58 years) who achieved uMRD, defined as having uMRD (<10–4 by 8-color flow cytometry) serially over at least three cycles and undetectable MRD in both peripheral blood (PB) and bone marrow (BM) with combination therapy, were randomised in a double-blinded fashion to continue treatment with ibrutinib monotherapy or placebo until disease progression.1

Patients in the MRD Guided Cohort who did not achieve uMRD following 12 cycles of combination ibrutinib plus venetoclax therapy were randomised to continue ibrutinib monotherapy or the combination.1 With a median total treatment duration of 28.6 months (range, 0.5-39.8) with ibrutinib and 12.0 months (range, 0.8-34.1) with venetoclax, increases in uMRD rates were greater with continued combination therapy versus continued ibrutinib monotherapy.1,2 Across all four randomised arms, 30-month progression-free survival rates were 95 percent or greater.1,2

The safety profile of the ibrutinib plus venetoclax regimen was consistent with known safety profiles of the individual therapies.1 Across all treated patients, the most common grade 3/4 adverse events (AEs) were neutropenia (36 percent), hypertension (10 percent), thrombocytopenia (5 percent), and diarrhoea (5 percent).1

"Ibrutinib is the only Bruton’s tyrosine kinase inhibitor that has shown significant overall survival and progression-free survival benefits in randomised Phase 3 studies in first-line CLL, and it continues to demonstrate efficacy and safety across regimens and patient subgroups, including those with historically poor outcomes," said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. "Results from the randomised phase of the MRD Guided Cohort of the CAPTIVATE study show that treatment-free remissions are possible with ibrutinib-based fixed duration therapy, providing yet another treatment option for patients starting first-line CLL treatment."

"Ibrutinib has impacted more than 200,000 patients worldwide and the CAPTIVATE study provides more evidence in support of the lasting effect that can be achieved in people living with CLL over time," adds Dr Catherine Taylor, Vice President, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd., Middle East. "The manageable safety profile of the ibrutinib combination with a low rate of discontinuation underscores this regimen as a potential viable option and we are excited to explore how it can benefit patients in a front-line setting."

The registrational Phase 3 GLOW study, assessing ibrutinib plus venetoclax in comparison to chlorambucil plus obinutuzumab for first-line treatment of elderly or younger unfit patients with CLL (NCT03462719) is ongoing as part of the comprehensive development programme exploring the potential of ibrutinib-based fixed duration therapy.3

*William Wierda is the lead investigator of the CAPTIVATE study. He was not compensated for any media work.

#ENDS#

About Ibrutinib
Ibrutinib is a once-daily, first-in-class Bruton’s tyrosine kinase (BTK) inhibitor that is administered orally, and is jointly developed and commercialised by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.4 Ibrutinib blocks the BTK protein; the BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signalling is needed by specific cancer cells to multiply and spread.5 By blocking BTK, ibrutinib may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.6

Indications for which ibrutinib is approved in Europe include:3

Chronic lymphocytic leukaemia (CLL): As a single agent or in combination with rituximab or obinutuzumab for the treatment of adult patients with previously untreated CLL, and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy
Mantle cell lymphoma (MCL): As a single agent for the treatment of adult patients with relapsed or refractory MCL
Waldenström’s macroglobulinemia (WM): As a single agent for the treatment of adult patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemo-immunotherapy, and in combination with rituximab for the treatment of adult patients
Ibrutinib is approved in more than 100 countries for at least one indication, and to date, has been used to treat more than 200,000 patients worldwide.7

For a full list of side effects and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics for further information.

About Chronic Lymphocytic Leukaemia
Chronic lymphocytic leukaemia (CLL) is typically a slow-growing blood cancer of the white blood cells.8 The overall incidence of CLL in Europe is approximately 4.92 cases per 100,000 persons per year and is about 1.5 times more common in men than in women.9 CLL is predominantly a disease of the elderly, with a median age of 72 years at diagnosis.10

The disease eventually progresses in the majority of patients, and they are faced with fewer treatment options with each relapse. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.

Reata Pharmaceuticals, Inc. Announces Closing of Class A Common Stock Offering

On December 4, 2020 Reata Pharmaceuticals, Inc. (Nasdaq: RETA) ("Reata" or the "Company"), a clinical-stage biopharmaceutical company, reported the closing of its previously announced underwritten public offering of 2,000,000 shares by the Company of its Class A common stock, at a price to the public of $140.85 per share, for gross proceeds of $281.7 million (Press release, Reata Pharmaceuticals, DEC 4, 2020, View Source [SID1234572231]). Reata has granted the underwriters a 30-day option to purchase 300,000 additional shares of its Class A common stock, on the same terms and conditions as the shares offered in the public offering.

Barclays Capital Inc. and Goldman Sachs & Co. LLC acted as the joint book-running managers for the offering.

The securities described above were offered pursuant to an automatically effective shelf registration statement on Form S-3. The offering was conducted only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A final prospectus supplement and accompanying prospectus relating to the offering have been filed with the Securities and Exchange Commission (the "SEC") and are available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus may also be obtained by request at Barclays Capital Inc., Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, telephone: 1-888-603-5847, or by emailing [email protected]; or Goldman Sachs & Co. LLC, Prospectus Department, 200 West Street, New York, NY 10282, telephone: 1-866-471-2526, facsimile: 212-902-9316 or by emailing [email protected].

This news release is for informational purposes only and 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 state or jurisdiction in which such offer, solicitation or sale of these securities would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

ASH: J&J links subcut BCMA bispecific to 73% response rate, plots aggressive investment

On December 3, 2020 Johnson & Johnson’s BCMAxCD3 bispecific antibody teclistamab reported that it has achieved a 73% overall response rate in a small trial of heavily pretreated multiple myeloma patients (Press release, Johnson & Johnson, DEC 4, 2020, View Source [SID1234572213]).

J&J presented data on an intravenous version of the drug in May, revealing eight of the 12 patients to get a certain dose responded to the therapy. Since then, J&J has moved a subcutaneous formulation of the bispecific antibody into a pivotal phase 2 clinical trial. J&J arrived at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting with data to support its decision to advance the formulation.

Sixteen of the 22 patients to receive the 1500 µg/kg subcutaneous phase 2 dose responded. Five participants had complete responses. All bar one of the responders was progression-free after median follow-up of 3.9 months.

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J&J achieved those responses without causing significant toxicity. While 64% of patients on the phase 2 subcutaneous dose experienced cytokine release syndrome, all those events were grade 1 or 2 and none caused a patient to discontinue. There was one grade 1, reversible neurotoxicity event. The mix of efficacy and tolerability seen to date has persuaded J&J to up its bet on teclistamab.

"It’s still early … but certainly the profile of teclistamab looks very, very promising to us and one that is worthy of aggressive investment and development. That’s the approach that we’re taking now," said Craig Tendler, vice president, oncology clinical development and global medical affairs at J&J.

An analysis of 11 patients who had complete responses to either the intravenous or subcutaneous formulations showed eight participants were minimal residual disease-negative at a threshold of 10-6.

The responses, which J&J said deepened over time, were seen in patients failed by multiple other therapies. Across the study, patients had received a median of six prior lines of treatment. Almost 40% of the participants were refractory to two or more immunomodulatory agents, two or more proteasome inhibitors and an anti-CD38 therapy. Such patients have few treatment options today.

"To be able to have a well-tolerated antibody be given that can get them into a very fast remission — time to first response is also quite quick — is certainly an important milestone for these patients in terms of getting their disease under control," Tendler said.

J&J is one of a considerable number of drug developers targeting BCMA to give relapsed/refractory multiple myeloma patients new options. Amgen, Bristol-Myers Squibb, Pfizer and Regeneron all have anti-BCMA bispecifics in development, GlaxoSmithKline is closing in on approval of an antibody-drug conjugate aimed at the target and a clutch of companies, including J&J, are working on cell therapies.

Initially, J&J, like its rivals, is going after heavily pretreated patients but it plans to move into earlier lines of therapy. J&J is testing the bispecific in combination with its anti-CD38 blockbuster Darzalex and has aspirations to establish it as a maintenance therapy and in the smoldering myeloma space. The switch from intravenous to subcutaneous formulations could benefit J&J’s push into other parts of the treatment pathway, including by enabling it to move away from weekly dosing.

"We have cohorts that will be looking at bi-weekly and then ultimately monthly dosing. That is definitely in the plan for further optimization of dosing, especially in settings like maintenance therapy. We want to have the most flexible dosing schedule so that this is not inconvenient for patients," Tendler said.

With other companies posting encouraging data and looking at subcutaneous formulations, J&J will face competition as it seeks to establish teclistamab but approaches the challenge on the back of its success reshaping multiple myeloma treatment with Darzalex.

PharmaEngine, Inc. and Sentinel Oncology Limited Enter into an Exclusive Collaboration and License Agreement for SOL-578, a Chk1 inhibitor

On December 4, 2020 PharmaEngine, Inc. (TWO: 4162) reported that it has entered into a Collaboration and License Agreement with UK-based Sentinel Oncology Limited for advancing the new drug development of SOL-578, a Checkpoint Kinase 1 (Chk1) inhibitor, under which PharmaEngine will fund the IND enabling studies for SOL-578 (Press release, PharmaEngine, DEC 4, 2020, View Source [SID1234572188]).

Sentinel Oncology Limited is a drug discovery company passionate about the development of novel therapeutics to treat cancer patients for whom there is currently an unmet medical need. The company’s mission is to increase survival and improve outcomes for cancer patients with CNS tumors. SOL-578 is a best-in-class checkpoint kinase 1 (Chk1) inhibitor featuring high kinase selectivity and oral bioavailability which targets the DNA Damage Response (DDR) network.

Under the terms of the Agreement, Sentinel Oncology will receive an exclusivity payment and PharmaEngine will obtain an option to receive the exclusive rights to develop and commercialize SOL-578 worldwide. In the event that PharmaEngine completes the IND enabling studies and exercise its option, Sentinel Oncology will be eligible to receive an upfront payment and development milestone payments in addition to tiered royalties based on future worldwide net sales of SOL-578.

"We are happy to collaborate with Sentinel Oncology Limited to activate the development of SOL-578." said Yufang Hu, Ph.D., President and CEO of PharmaEngine, Inc., "We are attracted by the dual function of SOL-578 in targeting the DDR signaling and cell cycle regulation axis in cancers. We believe that PharmaEngine can accelerate the development of this product based on our successful experience with a liposomal irinotecan, Onivyde."

About SOL-578

SOL-578 is a best-in-class checkpoint kinase 1 (Chk1) inhibitor featuring high kinase selective and oral bioavailability which targets the DNA Damage Response (DDR) network. Checkpoint kinases play a crucial role in the cellular response to DNA damage. Chk1 inhibitors potentiate the DNA-damaging effects of cytotoxic therapies and/or promote elevated levels of replication stress, leading to tumor cell death. SOL-578 has demonstrated single-agent activity in preclinical cancer models with high levels of replication stress.

Angiocrine Bioscience Announces Oral Presentation of AB-205 Data during the 62nd Annual Meeting of the American Society of Hematology (ASH)

On December 4, 2020 Angiocrine Bioscience Inc., a clinical-stage biopharmaceutical company reported that they have been selected by the American Society of Hematology (ASH) (Free ASH Whitepaper) for an oral presentation on the preliminary results of a Phase 1b/2 study of AB-205 to prevent or reduce severe organ toxicities associated with high-dose therapy followed by autologous hematopoietic cell transplantation used with curative intent in patients with aggressive systemic lymphoma (Press release, Angiocrine Bioscience, DEC 4, 2020, View Source [SID1234572187]).

"Our investigators and Angiocrine are honored to be selected by ASH (Free ASH Whitepaper) to present at its annual meeting this December," commented Paul Finnegan, MD, Angiocrine CEO. "We look forward to Dr. Michael Scordo’s presentation of AB-205’s efficacy and safety results from our Phase 1b/2 study as well as preparing for the upcoming Phase 3 registration study for this indication."

Session Name: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence I
Session Date: Saturday, December 5, 2020
Session Time: 7:30 AM – 9:00 AM ET
Presentation Time: 7:45 AM ET

About Severe Regimen-Related Toxicities
High-dose therapy and autologous hematopoietic cell transplantation is considered a standard-of-care method to cure aggressive systemic lymphoma. High dose therapy effectively eradicates cancer cells but also damages healthy tissue, which can lead to severe toxicities. Most affected is the lining of the oral-gastrointestinal (GI) tract. The oral GI tract renews its mucosal lining every 3 to 7 days. Because of the collateral damage from high dose chemotherapy, the oral GI tract loses its ability to renew its lining, leading to inflammation (mucositis) and breakdown, causing nausea, vomiting and diarrhea that are refractory to available medications and require prolonged hospitalization. Severe oral GI toxicities can occur as frequently as 50% and cause profound misery to patients. The rates and severity increase with age and, thus, many older patients are turned away from the curative high dose therapy due to the risks of severe toxicities.

About AB-205
AB-205 represents a new and unique approach to repairing damaged tissue through advanced cell-and-gene therapy. AB-205 consists of allogeneic (off-the shelf) ‘universal’ E-CEL (human engineered cord endothelial) cells. Intravenous AB-205 is given after chemotherapy/radiation (high-dose therapy) conditioning and on the same day as autologous transplant. AB-205’s immediate action repairs damaged tissue and thereby prevents (reduces) the extent of breakdown of tissues, which is the root cause of severe toxicities experienced by patients. Reducing or preventing severe toxicities means better quality of life and shorter stay in the hospital—i.e., savings to the healthcare system. AB-205 was recently granted both the Regenerative Medicine Advanced Therapy (RMAT) Designation and Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA). Angiocrine is actively planning to advance AB-205 into a multi-center single registration Phase 3 trial based on the results of the Phase 1b/2 study.