On April 28, 2022 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported its consolidated financial results for the first quarter ended March 31, 2022 and reviewed recent business highlights (Press release, Alnylam, APR 28, 2022, View Source [SID1234613115]).

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"The first quarter of 2022 saw a steady increase in patients on therapy across all products in our commercial portfolio, despite combined product revenues that were down compared to Q4 2021, as anticipated, given several non-recurring revenue benefits in the fourth quarter of 2021, as well as some pandemic-related impact experienced early in the quarter. We continue to make progress with our pipeline programs, including our TTR franchise, for which we reported positive 18-month results from the HELIOS-A study of vutrisiran, and we remain on track for topline results from the APOLLO-B study of patisiran in the middle of this year," said Yvonne Greenstreet, MBChB, MBA, Chief Executive Officer of Alnylam. "With our earlier stage programs, we’re excited to have initiated our first clinical study of an Alnylam investigational RNAi therapeutic targeting a CNS disorder with the start of our Phase 1 study for ALN-APP in patients with early-onset Alzheimer’s disease, and are announcing today that the Phase 1 study of ALN-XDH in patients with gout also has been initiated. These programs underscore our commitment to advancing innovative new medicines into the clinic, and we anticipate data from both programs later this year. We look forward to continuing our steady execution across our commercial products and advancement of our clinical development pipeline, with many key upcoming milestones to mark our progress toward achieving our Alnylam P5x25 strategy."

First Quarter 2022 and Recent Significant Corporate Highlights

Commercial Performance

ONPATTRO (patisiran)

Achieved global net product revenues for the first quarter of 2022 of $137 million, representing a 1% decrease compared to Q4 2021.
Attained over 2,200 hATTR amyloidosis patients with polyneuropathy worldwide on commercial ONPATTRO treatment as of March 31, 2022, up from over 2,050 commercial patients at year end 2021, representing 7% quarterly growth.
GIVLAARI (givosiran)

Achieved global net product revenues for the first quarter of 2022 of $35 million, representing a 13% decrease compared to Q4 2021.
Attained over 400 patients worldwide on commercial GIVLAARI treatment as of March 31, 2022, up from over 350 commercial patients at year end 2021, representing 14% quarterly growth.
OXLUMO (lumasiran)

Achieved global net product revenues for the first quarter of 2022 of $15 million, representing a 24% decrease compared to Q4 2021.
Attained over 160 patients worldwide on commercial OXLUMO treatment as of March 31, 2022, up from over 140 commercial patients at year end 2021, representing 14% quarterly growth.
Leqvio (inclisiran)

Launch in the U.S. and in other markets is ongoing, with focus on patient on-boarding, removing access hurdles and driving urgency to treat. Leqvio is now approved in more than 55 countries, with most awaiting reimbursement.
R&D Highlights

Vutrisiran, a subcutaneously administered investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis and Stargardt disease

Reported positive results for 18-month endpoints and safety from the HELIOS-A Phase 3 study in hATTR amyloidosis patients with polyneuropathy.
Vutrisiran met all 18-month secondary endpoints, including statistically significant improvements in neuropathy impairment, quality of life (QoL), gait speed, nutritional status and overall disability, relative to external placebo.
Vutrisiran continued to demonstrate halting or reversal of polyneuropathy, with improvements in neuropathy impairment and QoL, relative to baseline.
Additionally, vutrisiran continued to demonstrate an encouraging safety and tolerability profile.
At month 18, vutrisiran also showed improvements in exploratory cardiac endpoints, including NT-proBNP, a measure of cardiac stress; certain echocardiographic parameters, relative to placebo; and technetium uptake in the heart, providing potential evidence for reduced cardiac amyloid burden.
Announced that the U.S. Food and Drug Administration (FDA) has extended the review timeline of the New Drug Application (NDA) for vutrisiran to allow for review of newly added information related to the new secondary packaging and labeling facility.
The updated Prescription Drug User Fee Act (PDUFA) goal date to allow for this review is July 14, 2022. No additional clinical data have been requested by the FDA.
Vutrisiran is also under review by the European Medicines Agency (EMA), the Brazilian Health Regulatory Agency (ANVISA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA).
Lumasiran (the non-proprietary name for OXLUMO), for the treatment of primary hyperoxaluria type 1 (PH1), and in development for the treatment of recurrent kidney stone disease

Announced U.S. FDA acceptance of the Company’s supplemental NDA for OXLUMO for the treatment of advanced PH1.
The FDA has set a PDUFA goal date of October 6, 2022.
Additionally, a Type II variation for lumasiran to amend the label to further inform on the use of lumasiran in patients with advanced PH1 was submitted in December 2021 and is undergoing review by the Committee for Medicinal Products for Human Use (CHMP) with a decision expected by year-end.
Early- and mid-stage investigational RNAi therapeutic pipeline programs and RNAi platform

Initiated a Phase 1 study of ALN-APP in patients with early-onset Alzheimer’s disease (EOAD).
The Company announces today that it has initiated a Phase 1 study of ALN-XDH in patients with gout.
The Company announces today that, due in part to impacts related to COVID-19 as well as the ongoing situation in Ukraine, it now expects to complete enrollment in the KARDIA-1 Phase 2 monotherapy study of zilebesiran in patients with mild-to-moderate hypertension in early 2023, with topline results now expected in mid-2023.
Vir Biotechnology reported encouraging results from its Phase 2 trial evaluating ALN-HBV02 (VIR-2218), an investigational RNAi therapeutic in development for the treatment of chronic hepatitis B virus (HBV) infection, in combination with its investigational monoclonal antibody VIR-3434.
Additional Business Updates

Appointed Akshay Vaishnaw, M.D., Ph.D., formerly President, Research and Development, as President effective January 1, 2022.
Appointed Indrani Franchini as Chief Legal Officer effective January 31, 2022.
Entered into a collaboration with Novartis to explore a targeted therapy designed to promote the regrowth of functional liver cells and to provide an alternative to transplantation for patients with liver failure.
Launched a partnership with Our Future Health, the UK’s largest ever health research program that aims to genotype samples from up to 5 million participants.
Published 2021 Corporate Responsibility Report.
Filed separate patent infringement suits against Pfizer, Inc. and Moderna, Inc., seeking damages for infringement of U.S. Patent No. 11,246,933 in the parties’ manufacture and sale of their messenger RNA (mRNA) COVID-19 vaccines. The patent relates to Alnylam’s biodegradable cationic lipids that are foundational to the success of the mRNA COVID-19 vaccines.
Upcoming Events

In early and mid-2022, Alnylam intends to:

Launch vutrisiran in the U.S., assuming successful review and approval from the FDA, for the treatment of hATTR amyloidosis patients with polyneuropathy.
Report topline results from the APOLLO-B Phase 3 study of patisiran in ATTR amyloidosis patients with cardiomyopathy.
Report results from the Phase 2 monotherapy study of cemdisiran in patients with IgA nephropathy.
Novartis plans to report results from its ORION-3 Phase 2 study of inclisiran in patients with heterozygous familial hypercholesterolemia or pre-existing atherosclerotic cardiovascular disease on background statin +/- ezetimibe therapy.
Report topline results from Part B of the Phase 1 study of ALN-HSD in patients with NASH.
Financial Results for the Quarter Ended March 31, 2022

Net Product Revenues

Net product revenues increased 38% compared to the first quarter of 2021, primarily due to increased patients on ONPATTRO, GIVLAARI, and OXLUMO therapies, offset by an unfavorable impact from foreign exchange rates on our international revenue.
Net Revenues from Collaborations

Net revenues from collaborations decreased 38% compared to the first quarter of 2021, primarily due to a decrease in revenue from our collaboration with Regeneron.
First Quarter 2022 Expenses

Research & Development (R&D) Expenses

GAAP R&D expenses decreased compared to the first quarter of 2021, primarily due to decreased stock-based compensation expense primarily due to the accounting for certain performance-based awards.
Selling, General & Administrative (SG&A) Expenses

GAAP and Non-GAAP SG&A expenses increased compared to the first quarter of 2021, primarily due to increased legal expenses, charitable contributions, and other expenses to support our strategic growth. On a GAAP basis, these increases were offset by decreased stock-based compensation expense primarily due to the accounting for certain performance-based awards.
Other Financial Highlights

GAAP other expense increased compared to the first quarter of 2021, primarily due to approximately $80 million of realized and unrealized losses on our marketable equity securities holdings and an increase in interest expenses of approximately $10 million due to additional draws on our term loan facility.
Cash, cash equivalents and marketable securities were $2.24 billion as of March 31, 2022 compared to $2.44 billion as of December 31, 2021 with the decrease primarily due to our operating loss in the first quarter of 2022.
A reconciliation of our GAAP to non-GAAP results for the current quarter is included in the tables of this press release.

2022 Updated Financial Guidance
Full year 2022 financial guidance has been updated as follows:

Use of Non-GAAP Financial Measures

This press release contains non-GAAP financial measures, including expenses adjusted to exclude certain non-cash expenses and non-recurring gains outside the ordinary course of the Company’s business. These measures are not in accordance with, or an alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies.

The items included in GAAP presentations but excluded for purposes of determining non-GAAP financial measures for the periods presented in this press release are stock-based compensation expenses and realized and unrealized (gains) losses on marketable equity securities. The Company has excluded the impact of stock-based compensation expense, which may fluctuate from period to period based on factors including the variability associated with performance-based grants for stock options and restricted stock units and changes in the Company’s stock price, which impacts the fair value of these awards. The Company has excluded the impact of the realized and unrealized (gains) losses on marketable equity securities because the Company does not believe these adjustments accurately reflect the performance of the Company’s ongoing operations for the period in which such gains or losses are reported, as their sole purpose is to adjust amounts on the balance sheet.

The Company believes the presentation of non-GAAP financial measures provides useful information to management and investors regarding the Company’s financial condition and results of operations. When GAAP financial measures are viewed in conjunction with non-GAAP financial measures, investors are provided with a more meaningful understanding of the Company’s ongoing operating performance and are better able to compare the Company’s performance between periods. In addition, these non-GAAP financial measures are among those indicators the Company uses as a basis for evaluating performance, allocating resources and planning and forecasting future periods. Non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between GAAP and non-GAAP measures is provided later in this press release.

Conference Call Information

Management will provide an update on the Company and discuss first quarter 2022 results as well as expectations for the future via conference call on Thursday, April 28, 2022 at 8:30 am ET. To access the call, please dial 877-312-7507 (domestic) or +1-631-813-4828 (international) five minutes prior to the start time and refer to conference ID 2758447. A replay of the call will be available beginning at 11:30 am ET on the day of the call. To access the replay, please dial 855-859-2056 (domestic) or +1-404-537-3406 (international) and refer to conference ID 2758447.

A live audio webcast of the call will be available on the Investors section of the Company’s website at www.alnylam.com/events. An archived webcast will be available on the Alnylam website approximately two hours after the event.

About ONPATTRO (patisiran)

ONPATTRO is an RNAi therapeutic that was approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. ONPATTRO is also approved in the European Union, Switzerland and Brazil for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and in Japan for the treatment of hATTR amyloidosis with polyneuropathy. ONPATTRO is an intravenously administered RNAi therapeutic targeting transthyretin (TTR) and should be administered via a healthcare professional. It is designed to target and silence TTR messenger RNA, thereby blocking the production of TTR protein before it is made. ONPATTRO blocks the production of TTR in the liver, reducing its accumulation in the body’s tissues in order to halt or slow down the progression of the polyneuropathy associated with the disease. For more information about ONPATTRO, including please see the full U.S. Prescribing Information, visit ONPATTRO.com.

About GIVLAARI (givosiran)

GIVLAARI is an RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) approved in the United States and Brazil for the treatment of adults with acute hepatic porphyria (AHP). GIVLAARI is also approved in the European Union for the treatment of AHP in adults and adolescents aged 12 years and older. In the pivotal study, givosiran was shown to significantly reduce the rate of porphyria attacks that required hospitalizations, urgent healthcare visits or intravenous hemin administration at home compared to placebo. GIVLAARI is Alnylam’s first commercially available therapeutic based on its Enhanced Stabilization Chemistry ESC-GalNAc conjugate technology to increase potency and durability. GIVLAARI is administered via subcutaneous injection once monthly at a dose based on actual body weight and should be administered by a healthcare professional. GIVLAARI works by specifically reducing elevated levels of ALAS1 messenger RNA (mRNA), leading to reduction of toxins associated with attacks and other disease manifestations of AHP. For more information about GIVLAARI, including the full U.S. Prescribing Information, visit GIVLAARI.com.

About OXLUMO (lumasiran)

OXLUMO is an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate levels in pediatric and adult patients. HAO1 encodes glycolate oxidase (GO), an enzyme upstream of the disease-causing defect in PH1. OXLUMO works by degrading HAO1 messenger RNA and reducing the synthesis of GO, which inhibits hepatic production of oxalate – the toxic metabolite responsible for the clinical manifestations of PH1. In the pivotal ILLUMINATE-A study, OXLUMO was shown to significantly reduce levels of urinary oxalate relative to placebo, with the majority of patients reaching normal or near-normal levels. Injection site reactions (ISRs) were the most common drug-related adverse reaction. In the ILLUMINATE-B pediatric Phase 3 study, OXLUMO demonstrated an efficacy and safety profile consistent to that observed in ILLUMINATE-A. OXLUMO utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc conjugate technology designed to increase potency and durability. OXLUMO is administered via subcutaneous injection once monthly for three months, then once quarterly thereafter at a dose based on actual body weight. For patients who weigh less than 10 kg, ongoing dosing remains monthly. OXLUMO should be administered by a healthcare professional. For more information about OXLUMO, including the full U.S. Prescribing Information. visit OXLUMO.com.

About LNP Technology

Alnylam has licenses to Arbutus Biopharma LNP intellectual property for use in RNAi therapeutic products using LNP technology.

About RNAi

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

On April 28, 2022 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported that it will report first quarter 2022 financial results and provide a corporate update on Thursday, May 5, 2022 (Press release, Jounce Therapeutics, APR 28, 2022, View Source [SID1234613114]). Jounce Therapeutics’ management team will host a live conference call and webcast at 8:00 a.m. ET.

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Conference Call and Webcast
To access the conference call, please dial (866) 916-3380 (domestic) or (210) 874-7772 (international) and refer to conference ID 9072989. The live webcast can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at www.jouncetx.com. The webcast will be archived and made available for replay on the company’s website approximately two hours after the call and will be available for 30 days thereafter.

On April 28, 2022 Pfizer Inc. (NYSE: PFE) reported that its board of directors declared a $0.40 second-quarter 2022 dividend on the company’s common stock, payable June 10, 2022, to holders of the Common Stock of record at the close of business on May 13, 2022 (Press release, Pfizer, APR 28, 2022, View Source [SID1234613113]). The second-quarter 2022 cash dividend will be the 334th consecutive quarterly dividend paid by Pfizer.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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On April 28, 2022 Clovis Oncology, Inc. (NASDAQ: CLVS), reported that seven abstracts from the company’s pipeline, including late-breaking data from the ATHENA-MONO Phase 3 clinical trial evaluating Rubraca monotherapy versus placebo and imaging of solid tumors using FAP-2286, will be presented in oral and poster sessions during the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held June 3-7, 2022, in Chicago (Press release, Clovis Oncology, APR 28, 2022, View Source [SID1234613112]). Three additional retrospective analyses evaluating Rubraca and PARP inhibitors will be published online during the meeting.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"The wealth of data being presented during ASCO (Free ASCO Whitepaper), including more detailed analyses of the positive results from the ATHENA-MONO study of Rubraca monotherapy versus placebo in first-line maintenance treatment for ovarian cancer, adds to the breadth of knowledge demonstrating that Rubraca is an important part of treatment for patients regardless of biomarker status," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "Additionally, we look forward to new imaging data of FAP-2286 in solid tumors, an important component in understanding the solid tumor types where FAP-2286 may offer clinical benefit for patients."

The following non late breaker Clovis-sponsored and Clovis-supported abstracts will be available as of May 26 at 5:00 pm EDT on ASCO (Free ASCO Whitepaper)’s Meeting Library. The Clovis-sponsored late breaker abstract will be available as of June 6 at 8:00 a.m. EDT, and the posters and supplemental materials for all abstracts will be available on the day and at the time of presentation in the ASCO (Free ASCO Whitepaper) Program. In addition, Clovis-sponsored posters and supplemental materials can be found at View Source on the day and time of presentation.

Rubraca

Company-Sponsored Abstracts:

Abstract #LBA5500: ATHENA–MONO (GOG-3020/ENGOT-ov45): A randomized, double-blind, phase 3 trial evaluating rucaparib monotherapy versus placebo as maintenance treatment following response to first-line platinum-based chemotherapy in ovarian cancer

Lead Author: Bradley J. Monk., M.D., GOG Foundation, HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ, USA
Oral Abstract Session: Gynecologic Cancer
Date/Time: June 6, 9:00 a.m. – 12:00 p.m. EDT, presentation 9:00 – 9:12 a.m. EDT
Abstract #5544: Efficacy and safety of rucaparib maintenance treatment in patients from ARIEL3 with platinum-sensitive, recurrent ovarian carcinoma not associated with homologous recombination deficiency

Lead Author: Robert L. Coleman, FACS, M.D., FACOG, FASCO, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Poster Session: Gynecologic Cancer
Date/Time: June 4, 2:15 – 5:15 p.m. EDT
Company-Supported Abstracts:

Abstract #TPS9138: A Phase I/II multisite study of rucaparib and pembrolizumab maintenance therapy in stage IV non-squamous non-small cell lung cancer after initial therapy with carboplatin, pemetrexed, and pembrolizumab

Lead Author: Angel Qin, BS, M.D., University of Michigan, Rogel Cancer Center, Ann Arbor, MI, USA
Poster Session: Lung Cancer—Non-Small Cell Metastatic
Date/Time: June 6, 9:00 a.m. – 12:00 p.m. EDT
Abstract #TPS5107: Alliance A031902 (CASPAR): A randomized, phase (ph) 3 trial of enzalutamide with rucaparib/placebo in first-line metastatic castration-resistant prostate cancer (mCRPC)

Lead Author: Arpit Rao, M.D., Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
Poster Session: Genitourinary Cancer—Prostate, Testicular, and Penile
Date/Time: June 6, 2:15 – 5:15 p.m. EDT
Abstract #5510: An open label, nonrandomized, multisite phase II trial combining bevacizumab, atezolizumab, and rucaparib for the treatment of previously treated recurrent and progressive endometrial cancer

Lead Author: William Hampton Bradley, M.D., Froedtert and the Medical College of Wisconsin, Wauwatosa, WI, USA
Clinical Science Symposium: Molecular-Based Treatment for Endometrial Cancer
Date/Time: June 7, 9:00 – 10:30 a.m. EDT
ASCO Publication-Only Abstracts:

Abstract #e17562: Clinical experience with rucaparib after prior PARPi treatment: a subanalysis from the rucaparib access program in Spain by GEICO

Lead Author: Alfonso Yubero, M.D., Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
Abstract #e17598: Clinical insights from the rucaparib access program in Spain: a sub-analysis of long-term responders by GEICO

Lead Author: Alfonso Yubero, M.D., Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
Abstract #e18812: Real-world progression-free and overall survival for patients with advanced ovarian cancer utilizing PARP inhibitor second-line maintenance therapy vs active surveillance

Lead Author: Robert Reid, M.D., US Oncology, Medical Oncology, Virginia Cancer Specialists, Fairfax, VA, USA
FAP-2286

Company-Supported Abstract:

Abstract #3059: Imaging of solid tumors using 68Ga-FAP-2286

Lead Author: Thomas A. Hope, M.D., Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
Poster Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Date/Time: June 5, 9:00 a.m. – 12:00 p.m. EDT
For more information about FAP-2286, Targeted Radionuclide Therapy (TRT), or Clovis’ TRT development program, click here.

Lucitanib

Company-Sponsored Abstract:

Abstract #5517: Efficacy and safety of lucitanib + nivolumab in patients with advanced gynecologic malignancies: Phase 2 results from the LIO-1 study (NCT04042116; ENGOT-GYN3/AGO/LIO)

Lead Author: Manish R. Patel, M.D., Drug Development Unit, Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL, USA
Poster Discussion Session: Gynecologic Cancer
Date/Time: June 4, 5:30 – 7:00 p.m. EDT
Panel Q&A featuring Dr. Patel: 6:04 – 6:14 p.m. EDT
About Rubraca (rucaparib)

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca is an unlicensed medical product outside of the US and Europe.

Rubraca Ovarian Cancer US FDA Approved Indications

Rubraca is indicated for the maintenance treatment of adult women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Rubraca is indicated for the treatment of adult women with a deleterious BRCA mutation (germline and/or somatic)-associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) have occurred in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1146 treated patients, MDS/AML occurred in 20 patients (1.7%), including those in long term follow-up. Of these, 8 occurred during treatment or during the 28 day safety follow-up (0.7%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 53 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA damaging agents.

Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.

Based on its mechanism of action and findings from animal studies, Rubraca can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca.

Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1-4) were nausea (76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%), constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia (29%), nasopharyngitis/upper respiratory tract infection (29%), stomatitis (28%), decreased appetite (23%), and neutropenia (20%).

Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%; Grade 1-4) were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea (21%), and thrombocytopenia (21%).

Co-administration of rucaparib can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring.

Because of the potential for serious adverse reactions in breast-fed children from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks after the last dose.

Please Click here for full Prescribing Information for Rubraca.

You may also report side effects to Clovis Oncology, Inc. at 1-415-409-7220 (US toll) or 1-844-CLVS-ONC (1-844-258-7662; US toll-free).

Rubraca (rucaparib) European Union (EU) including Northern Ireland, and Great Britain (GB) authorized use and Important Safety Information

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rubraca is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with ≥2 prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Efficacy of Rubraca as treatment for relapsed or progressive epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) has not been investigated in patients who have received prior treatment with a PARP inhibitor. Therefore, use in this patient population is not recommended.

Summary warnings and precautions:

Hematological toxicity

During treatment with Rubraca, events of myelosuppression (anemia, neutropenia, thrombocytopenia) may be observed and are typically first observed after 8–10 weeks of treatment with Rubraca. These reactions are manageable with routine medical treatment and/or dose adjustment for more severe cases. Complete blood count testing prior to starting treatment with Rubraca, and monthly thereafter, is advised. Patients should not start Rubraca treatment until they have recovered from hematological toxicities caused by previous chemotherapy (CTCAE grade ≥1).

Supportive care and institutional guidelines should be implemented for the management of low blood counts for the treatment of anemia and neutropenia. Rubraca should be interrupted or dose reduced according to Table 1 (see Posology and Method of Administration [4.2] of the Summary of Product Characteristics [SPC]) and blood counts monitored weekly until recovery. If the levels have not recovered to CTCAE grade 1 or better after 4 weeks, the patient should be referred to a hematologist for further investigations.

MDS/AML

MDS/AML, including cases with fatal outcome, have been reported in patients who received Rubraca. The duration of therapy with Rubraca in patients who developed MDS/AML varied from less than 1 month to approximately 28 months.

If MDS/AML is suspected, the patient should be referred to a hematologist for further investigations, including bone marrow analysis and blood sampling for cytogenetics. If, following investigation for prolonged hematological toxicity, MDS/AML is confirmed, Rubraca should be discontinued.

Photosensitivity

Photosensitivity has been observed in patients treated with Rubraca. Patients should avoid spending time in direct sunlight because they may burn more easily during Rubraca treatment; when outdoors, patients should wear a hat and protective clothing, and use sunscreen and lip balm with sun protection factor of 50 or greater.

Gastrointestinal toxicities

Gastrointestinal toxicities (nausea and vomiting) are frequently reported with Rubraca and are generally low grade (CTCAE grade 1 or 2) and may be managed with dose reduction (refer to Posology and Method of Administration [4.2], Table 1 of the SPC) or interruption. Antiemetics, such as 5-HT3 antagonists, dexamethasone, aprepitant and fosaprepitant, can be used as treatment for nausea/vomiting and may also be considered for prophylactic (i.e. preventative) use prior to starting Rubraca. It is important to proactively manage these events to avoid prolonged or more severe events of nausea/vomiting which have the potential to lead to complications such as dehydration or hospitalization.

Embryofetal toxicity

Rubraca can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings from animal studies. In an animal reproduction study, administration of Rubraca to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at exposures below those in patients receiving the recommended human dose of 600 mg twice daily (see Preclinical Safety Data [5.3] of the SPC).

Pregnancy/contraception

Pregnant women should be informed of the potential risk to a fetus. Women of reproductive potential should be advised to use effective contraception during treatment and for 6 months following the last dose of Rubraca (see section 4.6 of the SPC). A pregnancy test before initiating treatment is recommended in women of reproductive potential.

Click here to access the current EU SmPC (including for Northern Ireland). Click here to access the current GB SmPC.

Healthcare professionals should report any suspected adverse reactions via their national reporting systems.

About the ATHENA Clinical Trial

ATHENA (GOG 3020/ENGOT-ov45) (NCT03522246) is an international, randomized, double-blind, phase III trial consisting of two separate and fully independently powered study comparisons evaluating Rubraca monotherapy (ATHENA-MONO) and Rubraca in combination with nivolumab (ATHENA-COMBO) as maintenance treatment for patients with newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. ATHENA enrolled approximately 1000 patients across 24 countries, all women with newly diagnosed ovarian cancer who responded to their first-line chemotherapy. The trial completed accrual in 2020 and was conducted in association with the Gynecologic Oncology Group (GOG) in the US and the European Network of Gynaecological Oncological Trial groups (ENGOT) in Europe. GOG and ENGOT are the two largest cooperative groups in the US and Europe dedicated to the treatment of gynecological cancers.

ATHENA-MONO is evaluating the benefit of Rubraca monotherapy versus placebo in 538 women in this patient population. The primary efficacy analysis evaluated two prospectively defined molecular sub-groups in a step-down manner: 1) HRD-positive (inclusive of BRCA mutant) tumors, and 2) the intent-to-treat population, or all patients treated in ATHENA-MONO.

The ATHENA-COMBO portion of the trial, anticipated to readout in Q1 2023, is evaluating the magnitude of benefit of adding Opdivo (nivolumab) to Rubraca monotherapy in the ovarian cancer first-line maintenance treatment setting. ATHENA-COMBO is anticipated to be the first Phase 3 dataset to readout evaluating the combination of a PARP inhibitor and an immune checkpoint inhibitor as maintenance treatment following completion and response to front-line chemotherapy.

About FAP-2286

FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two functional elements; a targeting peptide that binds to FAP and a site that can be used to attach radioactive isotopes for imaging and therapeutic use. High FAP expression has been shown in pancreatic ductal adenocarcinoma, cancer of unknown primary, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non–small cell lung, and squamous head and neck cancers. High FAP expression was detected in both primary and metastatic tumor samples and was independent of tumor stage or grade. Clovis holds US and global rights for FAP-2286 excluding Europe, Russia, Turkey, and Israel.

FAP-2286 is an unlicensed medical product.

About Targeted Radionuclide Therapy

Targeted radionuclide therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing delivery of radiation to normal tissue. Targeted radionuclides are created by linking radioactive isotopes, also known as radionuclides, to targeting molecules (e.g., peptides, antibodies, small molecules) that can bind specifically to tumor cells or other cells in the tumor environment. Based on the radioactive isotope selected, the resulting agent can be used to image and/or treat certain types of cancer. Agents that can be adapted for both therapeutic and imaging use are known as "theranostics." Clovis, together with licensing partner 3B Pharmaceuticals, is developing a pipeline of novel, targeted radiotherapies for cancer treatment and imaging, including its lead candidate, FAP-2286, an investigational peptide-targeted radionuclide therapeutic (PTRT) and imaging agent, as well as three additional discovery-stage compounds.

About the LuMIERE Clinical Study

LuMIERE is a Phase 1/2 study evaluating FAP-2286 as a peptide-targeted radionuclide therapy (PTRT) targeting fibroblast activation protein, or FAP, in patients with advanced solid tumors. The Phase 1 portion of the LuMIERE study is evaluating the safety of the investigational therapeutic agent and will identify the recommended Phase 2 dose and schedule of lutetium-177 labeled FAP-2286 (177Lu-FAP-2286). FAP-2286 labeled with gallium-68 (68Ga-FAP-2286) will be utilized as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment with the therapeutic agent. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types.

About Lucitanib

Lucitanib is an investigational angiogenesis inhibitor, which inhibits vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDGFRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR1-3). Emerging clinical data support the combination of angiogenesis inhibitors and immunotherapy to increase effectiveness in multiple cancer indications. Angiogenic factors, such as vascular endothelial growth factor (VEGF), are frequently up-regulated in tumors and create an immunosuppressive tumor microenvironment. Use of antiangiogenic drugs may reverse this immunosuppression and augment response to immunotherapy. Clovis holds global rights for lucitanib excluding China.

Lucitanib is an unlicensed medical product.

On April 28, 2022 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated oncology therapeutics, reported that it will report first quarter 2022 financial results on Thursday, May 5, 2022, after the close of U.S. markets (Press release, CytomX Therapeutics, APR 28, 2022, View Source [SID1234613111]). Following the announcement, the Company will host a conference call and webcast at 5:00 p.m. ET / 2:00 p.m. PT to discuss the results and provide a corporate update.

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Participants may access the live webcast of the conference call from the Events and Presentations page of CytomX’s website at View Source An archived replay of the webcast will be available on the Company’s website until May 12, 2022.