On February 14, 2022 The Janssen Pharmaceutical Companies of Johnson & Johnson reported initial results from the Phase 3 MAGNITUDE study evaluating the investigational use of niraparib, a selective poly-ADP ribose polymerase (PARP) inhibitor, in combination with abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) with or without specific homologous recombination repair (HRR) gene alterations (Press release, Johnson & Johnson, FEB 14, 2022, View Source [SID1234608095]). At the final analysis for radiographic progression-free survival (rPFS), the treatment combination of niraparib and abiraterone acetate plus prednisone demonstrated a statistically significant improvement in patients with HRR gene alterations. Results will be featured in a late-breaking oral presentation (Abstract #12; Oral Abstract Session A) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Genitourinary (ASCO GU) Cancers Symposium, taking place in San Francisco and virtually from February 17-19, 2022.

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MAGNITUDE (NCT03748641) is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of the combination of niraparib and abiraterone acetate plus prednisone as a first-line therapy in patients with mCRPC. The MAGNITUDE study was intentionally designed with two independent cohorts to assess treatment effect in patients with and without HRR gene alterations (including ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2 alterations) versus standard of care. The cohort of patients with prospectively-identified HRR gene alterations enrolled 423 patients, with patients randomized to receive the combination of niraparib and abiraterone acetate plus prednisone (combination arm [n=212]) or placebo and abiraterone acetate plus prednisone (control arm [n=211]). At 18.6-month median follow-up, patients in the combination arm of the cohort with HRR gene alterations showed a significant improvement in rPFS, with a reduction in the risk of progression or death of 27 percent (hazard ratio [HR] 0.73; p=0.022). This improvement was most pronounced in patients with BRCA1/2 gene alterations, where a 47 percent risk reduction was observed for rPFS (HR 0.53; p=0.001), as analyzed by blinded independent central review (BICR). A consistent but greater improvement was observed in investigator-assessed rPFS, which showed an overall 36 percent risk reduction in patients with HRR gene alterations (HR: 0.64; p=0.002), and a 50 percent risk reduction in patients with BRCA1/2 gene alterations (HR: 0.50; p=0.0006).1

The cohort without HRR gene alterations (n=233) met the predefined futility criteria in August 2020, showing no benefit from the treatment combination (HR>1) in the HRR biomarker negative population.1 Enrollment into this cohort was stopped at the time of futility at the recommendation of the Independent Data Monitoring Committee. Investigators and patients were unblinded and given the opportunity to continue treatment with niraparib and abiraterone acetate plus prednisone or receive only abiraterone acetate plus prednisone at the discretion of the study investigator.

"When choosing a treatment plan for patients with prostate cancer, physicians must consider individual needs, particularly for patients with mCRPC with HRR gene alterations who face a poor prognosis," said Dr. Kim Chi, Medical Oncologist at BC Cancer – Vancouver and principal investigator of the MAGNITUDE study.* "The MAGNITUDE data provide important context about the subgroup of patients with prostate cancer who may benefit from treatment with niraparib in combination with abiraterone acetate plus prednisone in the first-line setting, as well as those who may be better served by other treatment options."

In patients with HRR gene alterations, clinically relevant improvements in outcomes were also seen at this first interim analysis for secondary endpoints including time to initiation of cytotoxic chemotherapy, time to symptomatic progression and time to PSA progression. Additionally, objective response rate was improved by the combination of niraparib and abiraterone acetate plus prednisone. Overall survival data were immature at this interim analysis and follow-up will continue for all secondary endpoints.1

"These data suggest clinically meaningful improvements in outcomes in patients with prostate with HRR gene alterations who may derive benefit from this combination regimen, highlighting the importance of biomarkers to guide the patient selection process," said Mary Guckert, RN, MSN, Vice President, Development Leader, Prostate Cancer, Janssen Research & Development, LLC. "The design of this trial aligns with the real-world setting as it includes patients with prostate cancer who were able to start first-line standard of care treatment, while awaiting HRR biomarker results, and shows the need to prospectively test for and identify patients most likey to benefit from the combination of niraparib and abiraterone acetate with prednisone."

The observed safety profile of the combination of niraparib and abiraterone acetate plus prednisone was consistent with the known safety profile of each agent. Of the patients with HRR gene alterations, 67 percent experienced Grade 3 adverse events (AEs) and 46.4 percent experienced Grade 4 AEs, largely driven by anemia and fatigue. Discontinuation rates for the combination arm and control arm were 10.8 percent and 4.7 percent respectively. The combination of niraparib and abiraterone acetate plus prednisone also maintained overall quality of life in comparison with placebo and abiraterone acetate plus prednisone as measured on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) scale.1

Patients with HRR gene alterations, such as BRCA1/2, are at an increased risk of developing prostate cancer, and BRCA-related prostate cancer is usually aggressive.2 Long-term survival is low for patients with mCRPC and those who have HRR gene alterations face a worse prognosis, driving a significant unmet medical need for novel therapies in this disease.3,4

About MAGNITUDE
MAGNITUDE is a Phase 3 randomized, double-blind, placebo-controlled, multicenter clinical study evaluating the safety and efficacy of the combination of niraparib and abiraterone acetate plus prednisone as a first-line therapy for patients with mCRPC, with or without certain HRR gene alterations. The study includes two cohorts in which patients were randomized to receive either niraparib and abiraterone acetate plus prednisone or abiraterone acetate (placebo) plus prednisone cohorts: one cohort of patients with predefined HRR gene alterations (including ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2 alterations) and one cohort of patients without HRR gene alterations. In a third, open-label cohort, all patients received a combination tablet of niraparib and abiraterone and a separate tablet of prednisone. The primary endpoint of the MAGNITUDE trial is rPFS. Secondary endpoints include time-to-initiation of cytotoxic chemotherapy, time to symptomatic progression, and overall survival.

About Niraparib
Niraparib is an orally administered, selective poly-ADP ribose polymerase (PARP) inhibitor, that is currently being studied by Janssen for the treatment of patients with prostate cancer. Additional ongoing studies include the Phase 3 AMPLITUDE study evaluating the combination of niraparib and abiraterone acetate plus prednisone in a biomarker-selected patient population with metastatic castration-sensitive prostate cancer and QUEST, a Phase 1b/2 study of niraparib combination therapies for the treatment of mCRPC.

In April 2016, Janssen Biotech, Inc. entered a worldwide (except Japan) collaboration and license agreement with TESARO, Inc. (acquired by GSK in 2018), for exclusive rights to niraparib in prostate cancer. In the U.S., niraparib is indicated for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy; for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy; for the treatment of adult patients with advanced ovarian, fallopian tube or primary peritoneal cancer who have been treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either: a deleterious or suspected deleterious BRCA mutation, or genomic instability and who have progressed more than six months after response to the last platinum-based chemotherapy. Niraparib is currently marketed by GSK as ZEJULA.5

About Metastatic Castration-Resistant Prostate Cancer
Metastatic castration-resistant prostate cancer characterizes cancer that no longer responds to androgen deprivation therapy and has spread to other parts of the body. The most common metastatic sites are bones, followed by lymph nodes, lungs and liver.6 Prostate cancer is the second most common cancer in men worldwide, behind lung cancer.2 More than one million men around the world are diagnosed with prostate cancer each year.7 Patients with mCRPC and HRR gene alterations have a worse prognosis than those without HRR alterations.8

On February 14, 2022 Roivant Sciences reported that has spawned another Vant (Press release, Roivant Sciences, FEB 14, 2022, View Source [SID1234608336]). The latest addition to the clan is Hemavant, a biotech that starts life with a former Eisai drug and plans to start a study in patients with myelodysplastic syndromes (MDS) this year.

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Hemavant is developing RVT-2001, the small-molecule modulator of splicing factor 3B subunit 1 that Roivant licensed from Eisai late last year. Eisai, working with its H3 Biomedicine subsidiary, took the oral candidate into a phase 1 clinical trial in 2016 but saw no complete or partial responses in the first 84 patients enrolled in the study of patients with MDS and other blood cancers.

Work stalled on the candidate after the 2019 data drop, with Roivant saying in January that the number of subjects treated with RVT-2001 still stands at "over 80." Yet, Roivant sees promise in some of the data generated by Eisai, leading it to license the asset and narrow the focus of the program.

Eisai enrolled patients with acute myeloid leukemia, chronic myelomonocytic leukemia and lower- and higher-risk MDS in its phase 1 study. In that population, the lack of responses was a blow, but Roivant has zeroed in on another endpoint that suggests RVT-2001 may have a future in lower-risk, transfusion-dependent MDS patients.

RELATED: Roivant ditches plan to reacquire Immunovant, invests $200M

Thirty percent of the 19 lower-risk MDS patients treated with RVT-2001, formerly known as H3B 8800, gained red blood cell transfusion independence. Most of the patients had previously received Bristol Myers Squibb’s Revlimid, hypomethylating agents or both therapies.

Based on the signal, Hemavant is developing RVT-2001 as an oral therapy for transfusion-dependent anemia in patients with lower-risk MDS. A phase 1/2 clinical trial is set to start in the first half of the year.

Roivant has paid Eisai $8 million in cash and $7 million in stock for the global rights to the candidate. As RVT-2001 advances, Roivant will pay up to $65 million in development and regulatory milestones in the first indication plus up to $18 million in additional indications. The deal also features up to $295 million in commercial milestones and a tiered high single-digit to sub-teens royalty.

On February 14, 2022 Nykode Therapeutics AS (Euronext Growth (Oslo): NYKD), a clinical-stage biopharmaceutical company dedicated to the discovery and development of vaccines and novel immunotherapies, reported that its Chief Executive Officer, Michael Engsig, and Chief Innovation and Strategy Officer, Agnete Fredriksen, will present and provide a corporate update at the SVB Leerink 2022 Global Healthcare Conference on February 18, 2022 at 2.00 p.m. CET/ 8.00 a.m. EST and are available for 1:1 investor meetings (Press release, Nykode Therapeutics, FEB 14, 2022, View Source [SID1234608062]).

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An updated corporate presentation will be available in the Investors section of the Company’s website at 7:00 a.m. CET on February 18, 2022 at www.nykode.com/investors. The live and archived webcast of the presentation can be accessed in the Investors section of the Company’s website here.

On February 14, 2022 Bio-Techne Corporation (NASDAQ:TECH) reported an important publication in World Journal of Urology, entitled Pre–diagnosis urine exosomal RNA (ExoDx EPI score) is associated with post–prostatectomy pathology outcome (Press release, Bio-Techne, FEB 14, 2022, https://investors.bio-techne.com/news/detail/292/bio-techne-announces-publication-of-new-data-demonstrating-exodx-prostate-test-correlation-with-post-prostatectomy-pathology-outcomes [SID1234608078]). Principal investigator Dr. Alexander Kretschmer, urologist from Ludwig Maximilian University of Munich, Germany, and colleagues demonstrated utility of the ExoDx Prostate test, or EPI, to address limitations related to prostate biopsy sampling error, prostate biopsy bias as well as multifocality of the disease, providing a more relevant assessment of low-risk men who could remain on active surveillance. The significance of this study is that in men with an EPI score below the cut-point of 15.6, the ExoDx Prostate test could prevent low-risk men from proceeding to radical prostatectomy.

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According to the American Cancer Society, active surveillance is often used to monitor prostate cancer closely. Usually this includes a doctor visit with a prostate-specific antigen (PSA) blood test about every 6 months and a digital rectal exam at least once a year. Prostate biopsies and imaging tests may be done every 1 to 3 years. If test results change, the doctor would then discuss treatment options. Active surveillance is less invasive and a preferable option for men versus radical prostatectomy surgery that entails removal of the entire prostate gland and surrounding lymph nodes.

The study consisted of 2,066 subjects and explored the applicability of an exosome-based, non-invasive urine test for men with low-risk disease considering active surveillance. When EPI scores were evaluated for men with grade group 1 (GG1) on biopsy, those men who were upgraded to grade group 3 (≥GG3), had significantly higher scores compared to men that remained GG1 post radical prostatectomy. In contrast, neither PSA nor any of the standard multiparametric risk calculators provided any discrimination between these groups. Further, in this cohort, zero cases were upgraded to ≥GG3 when the EPI scores were below the cut-point of 15.6 resulting in a high NPV (100%) for ruling out ≥GG3.

The EPI test was previously validated in patients presenting for an initial biopsy as well as men with a prior negative biopsy. This study confirms that the ExoDx Prostate test also performs exceptionally well to predict which men will not be upgraded ≥GG3 at subsequent radical prostatectomy.

Prostate cancer (PCa) is a leading cause of cancer death among men in the United States, with more than 3.6 million men living with prostate cancer. It is estimated that more than 248,000 newly diagnosed cases occurred in 2021. A large percentage of newly diagnosed prostate cancers are indolent, clinically insignificant, and with low metastatic potential. These cancers typically do not require definitive treatment and may be managed most effectively with active surveillance. The low specificity of PSA which contributes to the high frequency of newly-diagnosed low-risk PCa suggests that 60–70% of men may be able to avoid biopsy.

Dr. Alexander Kretschmer, urologist from Ludwig Maximilian University of Munich, Munich, Germany, stated, "From the clinical perspective, active surveillance (AS) is still underused in eligible patients with low-risk localized prostate cancer and more tools are necessary to inform AS decisions. This study demonstrated the EPI test accurately identified men with GG1 at biopsy who remained GG1 post-radical prostatectomy (RP) compared to men upgraded to ≥ GG3 post-RP (p < 0.001). Since the EPI test was associated with low-risk pathology post-RP, and can be a valuable tool for urologists informing AS decisions."

"This study has important implications for up to 75% of men who would be eligible for an active surveillance program and potentially avoid radical prostatectomy," commented Chuck Kummeth, President and Chief Executive Officer of Bio-Techne Corporation. "Using ExoDx Prostate to predict which men can undergo active surveillance is an exciting and substantial advancement for men with a diagnosis of low-grade prostate cancer. The ExoDx Prostate Test provides the right intervention, for the right patient, at the right time."

On February 14, 2022 Tetra Bio-Pharma Inc. ("Tetra" or the "Company") (TSX: TBP) (OTCQB: TBPMF) (FRA:JAM1) a leader in cannabinoid-derived drug discovery and development reported that it has executed a non-binding term sheet with Avicanna Inc. ("Avicanna") (TSX: AVCN) (OTCQX: AVCNF) (FSE: 0NN) to assess entering into a strategic partnership comprising of three strategic pillars, including (Press release, Tetra Bio Pharma, FEB 14, 2022, View Source [SID1234608096]):

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The registration and commercialization of Tetra’s various prescription products (REDUVO AdVersa, QIXLEEF and CAUMZ) across Avicanna’s channels in Latin/South America. This opens the door for Tetra to initiate sales earlier than planned.
Supply of Avicanna’s Active Pharmaceutical Ingredients (APIs) for Tetra’s pharmaceutical pipeline. The phyto-cannabinoid APIs would be sourced from Avicanna’s low cost and sustainable operations in Colombia.
Co-development and support for Avicanna’s pharmaceutical pipeline for Health Canada and FDA level clinical development and registration.
Steeve Neron, Chief Commercial Officer at Tetra stated, "Tetra will need multiple reliable suppliers of API, like Avicanna, to support QIXLEEF operations leading to its successful marketing authorization and global sales and distribution. QIXLEEF is Tetra’s proprietary investigational new drug and is currently being evaluation in two U.S. FDA-authorized clinical trials. Additionally, Avicanna’s established distribution channels in Latin/South America may help advance Tetra’s product commercialization in select jurisdictions".

Aras Azadian, Chief Executive Officer of Avicanna also commented on the opportunity. "We look forward to collaborating with the Tetra team who has in many ways been pioneering cannabinoid- prescription products. As the global industry continues to mature and shift its focus towards evidence-based medicines, the two companies are well positioned to work in synergy across several projects and leverage their leadership positions into fruitful commercial results."