On January 8, 2024 Pfizer Inc. (NYSE: PFE) reported that the European Commission (EC) has approved TALZENNA (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with XTANDI (enzalutamide), for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated (Press release, Seagen, JAN 8, 2024, View Source [SID1234639110]). With this approval, TALZENNA is now the first and only PARP inhibitor licensed in the European Union for use with XTANDI for patients with mCRPC, with or without gene mutations.

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"New treatment options are needed to increase the proportion of patients with metastatic castration-resistant prostate cancer who can benefit from current anticancer medicines that keep the disease under control for longer," said Robert Jones, MBChB, PhD, Professor of Clinical Cancer Research, University of Glasgow. "The European Commission’s approval of talazoparib in combination with enzalutamide offers a meaningful advancement for the treatment of patients with metastatic castration-resistant prostate cancer, the most advanced and aggressive stage of the disease."

"After years of fighting prostate cancer, it can be devastating for a patient to learn that their cancer has stopped responding to testosterone-lowering treatments. At this stage of the disease, the prognosis is generally poor," said Erik Briers, MS, PhD, Vice Chairman, Europa UOMO, a European advocacy movement for people with prostate cancer. "Patients urgently need new treatment options and TALZENNA in combination with XTANDI can bring new hope to these patients."

This approval by the European Commission of TALZENNA in combination with XTANDI for the mCRPC indication is valid in all 27 EU member states plus Iceland, Liechtenstein, and Norway.

The approval is based on data from the Phase 3 TALAPRO-2 trial, a multicenter, randomized, double-blind, placebo-controlled study, evaluating two mCRPC patient cohorts: Cohort 1 (all-comers [n=805]) and Cohort 2 (those with HRR gene mutations [HRRm; n=399]). The results from TALAPRO-2 Cohort 1, which were published in The Lancet, showed that treatment with TALZENNA plus XTANDI reduced the risk of disease progression or death by 37% versus placebo plus XTANDI (Hazard Ratio [HR]: 0.63; 95% Confidence Interval [CI], 0.51–0.78; P< 0.0001), meeting the study’s primary endpoint of improving radiographic progression-free survival (rPFS). At the time of the analysis, the median rPFS for those treated with TALZENNA plus XTANDI had not yet been reached versus 21.9 months for those treated with placebo plus XTANDI. Median rPFS is defined as the timepoint in which 50% of patients in each treatment arms have progressed. A trend in overall survival (OS), a key secondary endpoint, favoring TALZENNA plus XTANDI was also observed, though these data are immature. The safety of TALZENNA plus XTANDI in the TALAPRO-2 trial was generally consistent with the known safety profile of each medicine.

"Today’s approval of TALZENNA in combination with XTANDI represents an important advancement for men living with prostate cancer in Europe," said Chris Boshoff, M.D., Ph.D., Chief Oncology Officer, Executive Vice President, Pfizer. "The results from the pivotal TALAPRO-2 trial showed that this combination offers an effective treatment that addresses disease progression in patients with or without any specific gene mutation."

TALZENNA in combination with XTANDI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with HRR gene-mutated mCRPC in June 2023. Pfizer has also shared the TALAPRO-2 data with other regulatory agencies to support regulatory filings.

About Metastatic Castration-Resistant Prostate Cancer

Metastatic castration-resistant prostate cancer (mCRPC) is a cancer that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone. There were ~1.4 million new cases of prostate cancer reported worldwide in 2020, of which ~470,000 new cases were in Europe.1 Approximately 10%–20% of prostate cancer patients develop mCRPC within 5−7 years of diagnosis.2 Between 1.2%–2.1% of all prostate cancer cases globally are mCRPC.3

About TALAPRO-2

The Phase 3 TALAPRO-2 trial is a two-part, two-cohort, multicenter, randomized, double-blind, placebo-controlled study that enrolled 1,106 patients with mCRPC (with no systemic treatments initiated after documentation of mCRPC) at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. The study included two patient cohorts: all-comers (n=805) and those with and without gene mutations (HRRm; n=399). Patients on androgen deprivation therapy (ADT) or who had bilateral orchiectomy in the trial were randomized to receive TALZENNA 0.5 mg/day plus XTANDI 160mg/day, or placebo plus XTANDI 160 mg/day.

The primary endpoint of the trial is radiographic progression-free survival (rPFS), defined as the time from the date of randomization to first objective evidence of radiographic progression by blinded independent review, or death, whichever occurs first, in both Cohort 1 (all-comers) and Cohort 2 (those with HRRm). Secondary endpoints include overall survival (OS), objective response rate, duration of response, and PSA response.

For more information on the TALAPRO-2 trial (NCT03395197), go to www.clinicaltrials.gov.

About TALZENNA (talazoparib)

TALZENNA (talazoparib) is an oral inhibitor of poly ADP-ribose polymerase (PARP), which plays a role in DNA damage repair. Preclinical studies have demonstrated that TALZENNA blocks PARP enzyme activity and traps PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death.

TALZENNA is approved in over 70 countries, including the U.S and the EU, as a once-daily monotherapy for the treatment of adult patients with deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA)-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer. In the U.S., TALZENNA is approved in combination with XTANDI (enzalutamide) for the treatment of adult patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). In the EU, TALZENNA is now approved in combination with enzalutamide for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated.

TALZENNA (talazoparib) Indication in the U.S.

TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for:

Breast Cancer:

As a single agent, for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved companion diagnostic for TALZENNA.
HRR Gene-mutated mCRPC:

In combination with enzalutamide for the treatment of adult patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).
TALZENNA (talazoparib) Important Safety Information

WARNINGS and PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including cases with a fatal outcome, has been reported in patients who received TALZENNA. Overall, MDS/AML has been reported in 0.4% (3 out of 788) of solid tumor patients treated with TALZENNA as a single agent in clinical studies. In TALAPRO-2, MDS/AML occurred in 2 out of 511 (0.4%) patients treated with TALZENNA and enzalutamide and in 0 out of 517 (0%) patients treated with placebo and enzalutamide. The durations of TALZENNA treatment in these five patients prior to developing MDS/AML were 0.3, 1, 2, 3, and 5 years, respectively. Most of these patients had received previous chemotherapy with platinum agents and/or other DNA damaging agents including radiotherapy.

Do not start TALZENNA until patients have adequately recovered from hematological toxicity caused by previous chemotherapy. Monitor blood counts monthly during treatment with TALZENNA. For prolonged hematological toxicities, interrupt TALZENNA and monitor blood counts weekly until recovery. If counts do not recover within 4 weeks, refer the patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue TALZENNA.

Myelosuppression consisting of anemia, neutropenia, and/or thrombocytopenia have been reported in patients treated with TALZENNA. In TALAPRO-2, Grade ≥3 anemia, neutropenia, and thrombocytopenia were reported, respectively, in 45%, 18%, and 8% of patients receiving TALZENNA and enzalutamide. Overall, 39% of patients (199/511) required a red blood cell transfusion, including 22% (111/511) who required multiple transfusions. Discontinuation due to anemia, neutropenia, and thrombocytopenia occurred, respectively, in 7%, 3%, and 0.4% of patients.

Withhold TALZENNA until patients have adequately recovered from hematological toxicity caused by previous therapy. Monitor blood counts monthly during treatment with TALZENNA. If hematological toxicities do not resolve within 28 days, discontinue TALZENNA and refer the patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics.

Embryo-Fetal Toxicity TALZENNA can cause fetal harm when administered to pregnant women. Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment with TALZENNA and for 4 months after receiving the last dose.

ADVERSE REACTIONS

Serious adverse reactions reported in >2% of patients included anemia (9%) and fracture (3%). Fatal adverse reactions occurred in 1.5% of patients, including pneumonia, COVID infection, and sepsis (1 patient each).

The most common adverse reactions (≥ 10%, all Grades), including laboratory abnormalities, for patients in the TALAPRO-2 study who received TALZENNA in combination with enzalutamide vs patients receiving placebo with enzalutamide were hemoglobin decreased (79% vs 34%), neutrophils decreased (60% vs 18%), lymphocytes decreased (58% vs 36%), fatigue (49% vs 40%), platelets decreased (45% vs 8%), calcium decreased (25% vs 11%), nausea (21% vs 17%), decreased appetite (20% vs 14%), sodium decreased (22% vs 20%), phosphate decreased (17% vs 13%), fractures (14% vs 10%), magnesium decreased (14% vs 12%), dizziness (13% vs 9%), bilirubin increased (11% vs 7%), potassium decreased (11% vs 7%), and dysgeusia (10% vs 4.5%).

Clinically relevant adverse reactions in <10% of patients who received TALZENNA with enzalutamide included abdominal pain (9%), vomiting (9%), alopecia (7%), dyspepsia (4%), venous thromboembolism (3%) and stomatitis (2%).

Based on animal studies, TALZENNA may impair fertility in males of reproductive potential.

DRUG INTERACTIONS

Coadministration with P-gp inhibitors The effect of coadministration of P-gp inhibitors on talazoparib exposure when TALZENNA is taken in combination with enzalutamide has not been studied. Monitor patients for increased adverse reactions and modify the dosage as recommended for adverse reactions when TALZENNA is coadministered with a P-gp inhibitor.

Coadministration with BCRP inhibitors Monitor patients for increased adverse reactions and modify the dosage as recommended for adverse reactions when TALZENNA is coadministered with a BCRP inhibitor. Coadministration of TALZENNA with BCRP inhibitors may increase talazoparib exposure, which may increase the risk of adverse reactions.

USE IN SPECIFIC POPULATIONS

Renal Impairment The recommended dosage of TALZENNA for patients with moderate renal impairment (CLcr 30 – 59 mL/min) is 0.35 mg taken orally once daily in combination with enzalutamide. The recommended dosage of TALZENNA for patients with severe renal impairment (CLcr 15 – 29 mL/min) is 0.25 mg taken orally once daily in combination with enzalutamide. No dose adjustment is required for patients with mild renal impairment. TALZENNA has not been studied in patients requiring hemodialysis.

Please see full U.S. Prescribing Information and Patient Information for TALZENNA (talazoparib) at www.TALZENNA.com.

About XTANDI (enzalutamide) and Important Safety Information

XTANDI (enzalutamide) is an androgen receptor signaling inhibitor. XTANDI is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic castration-sensitive prostate cancer (mCSPC; also known as metastatic hormone-sensitive prostate cancer or mHSPC), metastatic castration-resistant prostate cancer (mCRPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR). XTANDI is currently approved for one or more of these indications in more than 90 countries, including in the U.S., EU, and Japan. Over one million patients have been treated with XTANDI globally.4

Warnings and Precautions

Seizure occurred in 0.6% of patients receiving XTANDI in eight randomized clinical trials. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Patients in the study had one or more of the following predisposing factors: use of medications that may lower the seizure threshold, history of traumatic brain or head injury, history of cerebrovascular accident or transient ischemic attack, and Alzheimer’s disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) There have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder that can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in eight randomized clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.

Ischemic Heart Disease In the combined data of five randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (3.5% vs 2%). Grade 3-4 ischemic events occurred in 1.8% of patients on XTANDI versus 1.1% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.

Falls and Fractures occurred in patients receiving XTANDI. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. In the combined data of five randomized, placebo-controlled clinical studies, falls occurred in 12% of patients treated with XTANDI compared to 6% of patients treated with placebo. Fractures occurred in 13% of patients treated with XTANDI and in 6% of patients treated with placebo.

Embryo-Fetal Toxicity The safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI.

Adverse Reactions (ARs)

In the data from the five randomized placebo-controlled trials, the most common ARs (≥ 10%) that occurred more frequently (≥ 2% over placebo) in XTANDI-treated patients were musculoskeletal pain, fatigue, hot flush, constipation, decreased appetite, diarrhea, hypertension, hemorrhage, fall, fracture, and headache. In the bicalutamide-controlled study, the most common ARs (≥ 10%) reported in XTANDI-treated patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.

In AFFIRM, the placebo-controlled study of metastatic CRPC (mCRPC) patients who previously received docetaxel, Grade 3 and higher ARs were reported among 47% of XTANDI-treated patients. Discontinuations due to ARs were reported for 16% of XTANDI-treated patients. In PREVAIL, the placebo-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to ARs were reported for 6% of XTANDI-treated patients. In TERRAIN, the bicalutamide-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 39% of XTANDI patients and 38% of bicalutamide patients. Discontinuations with an AR as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients.

In PROSPER, the placebo-controlled study of nonmetastatic CRPC (nmCRPC) patients, Grade 3 or higher ARs were reported in 31% of XTANDI patients and 23% of placebo patients. Discontinuations with an AR as the primary reason were reported for 9% of XTANDI patients and 6% of placebo patients.

In ARCHES, the placebo-controlled study of metastatic CSPC (mCSPC) patients, Grade 3 or higher ARs were reported in 24% of XTANDI-treated patients. Permanent discontinuation due to ARs as the primary reason was reported in 5% of XTANDI patients and 4% of placebo patients.

In EMBARK, the placebo-controlled study of nonmetastatic CSPC (nmCSPC) with high-risk biochemical recurrence (BCR) patients, Grade 3 or higher adverse reactions during the total duration of treatment were reported in 46% of patients treated with XTANDI plus leuprolide, 50% of patients receiving XTANDI as a single agent, and 43% of patients receiving placebo plus leuprolide. Permanent treatment discontinuation due to adverse reactions during the total duration of treatment as the primary reason was reported in 21% of patients treated with XTANDI plus leuprolide, 18% of patients receiving XTANDI as a single agent, and 10% of patients receiving placebo plus leuprolide.

Lab Abnormalities: Lab abnormalities that occurred in ≥ 5% of patients, and more frequently (> 2%) in the XTANDI arm compared to placebo in the pooled, randomized, placebo-controlled studies are hemoglobin decrease, neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, hyperphosphatemia, and hypercalcemia.

Hypertension: In the combined data from five randomized placebo-controlled clinical trials, hypertension was reported in 14.2% of XTANDI patients and 7.4% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid coadministration with strong CYP2C8 inhibitors. If coadministration cannot be avoided, reduce the dosage of XTANDI.

Avoid coadministration with strong CYP3A4 inducers. If coadministration cannot be avoided, increase the dosage of XTANDI.

Effect of XTANDI on Other Drugs Avoid coadministration with certain CYP3A4, CYP2C9, and CYP2C19 substrates for which minimal decrease in concentration may lead to therapeutic failure of the substrate. If coadministration cannot be avoided, increase the dosage of these substrates in accordance with their Prescribing Information. In cases where active metabolites are formed, there may be increased exposure to the active metabolites.

Please see Full Prescribing Information for additional safety information.

On January 8, 2024 Royalty Pharma plc (Nasdaq: RPRX) reported an update on its business performance, including recent key accomplishments, and the full year 2023 outlook for Portfolio Receipts (Press release, Royalty Pharma , JAN 8, 2024, View Source [SID1234639108]). Pablo Legorreta, Royalty Pharma’s founder and Chief Executive Officer, will discuss these updates tomorrow as part of a webcast presentation at the 42nd Annual J.P. Morgan Healthcare Conference to be held at 12:00 p.m. Eastern Time / 9:00 a.m. Pacific Time.

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"Royalty Pharma delivered record performance in 2023," said Pablo Legorreta. "We expect to achieve an all-time high for Portfolio Receipts of approximately $3.05 billion, representing our third consecutive year of double-digit underlying growth since our initial public offering in 2020. We deployed substantial capital to acquire royalties on eight therapies, including our strongest year ever for synthetic royalty transactions. We remain in an excellent position to deliver compounding growth in the years to come while executing on our mission and vision to accelerate innovation in life sciences and transform patient lives globally."

Record 2023 Financial Performance

Based on preliminary unaudited fourth quarter 2023 results, Royalty Pharma now expects to deliver Portfolio Receipts for full year 2023 of approximately $3,050 million, which includes a $50 million payment related to oral zavegepant and exceeds the upper end of its previous guidance range of $2,950 million to $3,000 million. This represents underlying growth of 11% year-over-year prior to Biohaven-related payments and reflects the strong performance of Royalty Pharma’s diversified royalty portfolio. Royalty Pharma also expects Net cash provided by operating activities to be approximately $2,980 million to $2,990 million for full year 2023.

Portfolio Receipts was previously referred to as Adjusted Cash Receipts. The calculation of Portfolio Receipts will result in the same total as under Royalty Pharma’s previous presentation of Adjusted Cash Receipts. This change of presentation will facilitate increased transparency into the economics of individual royalties, as Royalty Receipts by product and franchise, will be reported net of legacy non-controlling interests.

Royalty Pharma’s preliminary unaudited fourth quarter 2023 results provided in this press release are subject to change in connection with the completion of the company’s final adjustments and other developments that may arise during the preparation and audit of its financial statements. Royalty Pharma’s management will host a conference call to discuss Royalty Pharma’s fourth quarter and full year 2023 results in February 2024.

Strong Capital Deployment Added Innovative Therapies, Enhancing Long-term Growth

Since 2020, Royalty Pharma has announced transactions of approximately $13 billion, including $4.0 billion in 2023. Important additions to Royalty Pharma’s portfolio in the past year have included incremental royalties on Evrysdi, the fast-growing therapy for spinal muscular atrophy, as well as the potentially practice-changing, development-stage compounds pelacarsen for cardiovascular disease and KarXT for schizophrenia. Royalty Pharma also had its strongest year ever for synthetic royalties with announced transactions of $775 million, including Adstiladrin for bladder cancer, which is the first gene therapy added to its portfolio, Skytrofa, an approved therapy for growth hormone deficiency and TEV-‘749, an exciting development-stage compound for schizophrenia.

In total, 34 unique therapies have been added to the company’s portfolio since 2020 (of which 17 are either currently or projected to be blockbusters that generate annual sales of $1 billion or more based on consensus estimates). In aggregate, based on consensus sales forecasts, investments made since 2020 are estimated to add approximately $1.2 billion to Royalty Pharma’s Portfolio Receipts in 2025.

Biopharma Funding Environment Driving New Royalty Opportunities

The biopharmaceutical ecosystem is generating significant demand for capital to fund the ongoing wave of healthcare innovation. Reflecting this positive market backdrop, between 2019 and 2023, the number of in-depth reviews of new royalty opportunities conducted by Royalty Pharma increased by 133%, resulting in an 80% increase in announced annual transaction value (from $2.2 billion in 2019 to $4.0 billion in 2023).

Given Royalty Pharma’s unique role at the heart of funding life sciences innovation, Royalty Pharma believes that there will be significant opportunity to deploy capital and fund innovation, while creating value for its stakeholders. This is reflected in the company’s capital deployment target of $10 billion to $12 billion from 2022 to 2026 and in Royalty Pharma’s expectation that it has the potential over the longer term to double its average annual capital deployment to $4 billion to $5 billion.

Webcast of J.P. Morgan Healthcare Conference

Royalty Pharma will present at the 42nd Annual J.P. Morgan Healthcare Conference at 12:00 p.m. ET / 9:00 a.m. PT tomorrow. The webcast will be accessible from Royalty Pharma’s "Events" page at View Source The webcast will also be archived for a minimum of thirty days.

On January 8, 2024 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported a business update including preliminary total revenue for the fourth quarter of 2023, ongoing activity from the commercial portfolio, including TAVALISSE (fostamatinib disodium hexahydrate) tablets and REZLIDHIA (olutasidenib) capsules, and upcoming catalysts for 2024 (Press release, Rigel, JAN 8, 2024, View Source [SID1234639107]).

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"2023 was a year of significant growth across our commercial hematology-oncology portfolio. We grew TAVALISSE net product sales nearly 24% over 2022 and successfully achieved more than $10 million of REZLIDHIA revenue during its first full year of launch. This enabled us to generate more than $104 million of total net product sales this year," said Raul Rodriguez, Rigel’s president and CEO. "Also, our recent collaborations with MD Anderson and CONNECT will allow us to evaluate the potential of REZLIDHIA as a possible therapy in a broad range of IDH1-mutant cancers. As we head into the future, we are focused on commercial execution, the advancement of our hematology-oncology pipeline, and our plan to reach financial breakeven."

Commercial and Preliminary Financial Update
In the fourth quarter of 2023, a total of 2,671 bottles of TAVALISSE were sold in the U.S., of which, 2,463 bottles were shipped directly to patients and clinics, representing the highest daily bottles shipped to patients and clinics in a quarter since launch. While Rigel is still determining final results for the fourth quarter of 2023, it expects to report net product sales of TAVALISSE of $25.7 million for the fourth quarter compared to $21.9 million for the same period of 2022.

In the fourth quarter of 2023, a total of 308 bottles of REZLIDHIA were sold in the U.S., of which, 278 bottles were shipped directly to patients and clinics. While Rigel is still determining final results for the fourth quarter of 2023, it expects to report net product sales of REZLIDHIA of $3.9 million for the fourth quarter compared to $0.9 million for the same period of 2022.

Overall, Rigel expects to report net product sales of $104.3 million in 2023, representing 36% growth over 2022.

Contract revenues for the fourth quarter of 2023 are expected to be approximately $6.1 million, consisting of $6.0 million in contract revenue from collaborations and $0.1 million in government contract revenue. Contract revenue from collaborations is expected to include $3.7 million of revenue from Grifols S.A., related to delivery of drug supplies and earned royalties, as well as $2.2 million of revenue from Kissei Pharmaceutical Co., Ltd. and $0.1 million of revenue from Medison Pharma Trading AG, related to delivery of drug supplies.

For the fourth quarter of 2023, Rigel expects to report total revenue of approximately $35.7 million.

Rigel expects to report cash, cash equivalents, and short-term investments of approximately $56.9 million as of December 31, 2023, compared to $58.2 million as of December 31, 2022.

The above information is preliminary, has not been audited, and is subject to change upon the audit of Rigel’s financial statements for the year ended December 31, 2023. Rigel expects to provide complete fourth quarter and full year 2023 financial results in March 2024.

Q4 Business Update

Rigel and The University of Texas MD Anderson Cancer Center (MD Anderson) recently announced a multi-year strategic development collaboration to expand the evaluation of REZLIDHIA (olutasidenib) in acute myeloid leukemia (AML) and other hematologic cancers. Under the strategic collaboration, Rigel and MD Anderson will evaluate the potential of olutasidenib to treat newly diagnosed and relapsed or refractory (R/R) patients with AML, higher-risk myelodysplastic syndromes (MDS), and advanced myeloproliferative neoplasms (MPN), in combination with other agents. The collaboration will also support the evaluation of olutasidenib as monotherapy in lower-risk MDS and maintenance therapy in post-hematopoietic stem cell transplant (HSCT) patients. Rigel will provide $15 million in time-based milestone payments and study material over the five-year collaboration.

Rigel and CONNECT recently announced a collaboration to evaluate REZLIDHIA (olutasidenib) in combination with temozolomide as maintenance therapy in patients with high-grade glioma (HGG) harboring an isocitrate dehydrogenase-1 (IDH1) mutation. Under the collaboration, CONNECT will include olutasidenib in CONNECT’s TarGeT-D, a molecularly guided Phase 2 umbrella clinical trial for HGG. The Rigel-sponsored arm will study post-radiotherapy administration of olutasidenib in combination with temozolomide followed by olutasidenib monotherapy as maintenance treatment in newly diagnosed pediatric and young adult patients (<39 years old) with IDH1 mutation positive HGG, including diffuse intrinsic pontine glioma (DIPG), an aggressive brain tumor with limited treatment options. Rigel will provide funding up to $3 million and study material over the four-year collaboration.

In December 2023, Rigel presented four posters highlighting data from the Company’s commercial and clinical-stage hematology-oncology portfolio at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. Included was a poster, Abstract #2888, reporting post hoc analyses in a subset of patients with mIDH1 R/R AML or MDS that were R/R to HSCT, ivosidenib, or venetoclax. The analyses suggest that olutasidenib alone or in combination with azacitidine may induce complete remissions in these patients.

Rigel continues to advance its open-label, Phase 1b clinical trial of R2891, an investigational, potent, and selective IRAK1/4 inhibitor, in patients with lower-risk myeloid dysplastic syndrome (LR-MDS) who are refractory/resistant to prior therapies. The primary endpoint for this trial is safety with key secondary endpoints including preliminary efficacy and evaluation of pharmacokinetic properties. Rigel is currently enrolling patients in the third cohort.
About ITP
In patients with ITP (immune thrombocytopenia), the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs), and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

About AML
Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that in the United States alone, there were about 20,380 new cases, most in adults, in 2023.2

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need.

About R289
R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which has been shown in preclinical studies to block inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to various inflammatory conditions. Chronic stimulation of both these receptor systems is thought to cause the pro-inflammatory environment in the bone marrow responsible for persistent cytopenias in lower-risk MDS patients.5

About TAVALISSE
Indication
TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information
Warnings and Precautions

Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
Drug Interactions

Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
Adverse Reactions

Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.
Please see www.TAVALISSEUSPI.com for Full Prescribing Information.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

TAVALISSE is a registered trademark of Rigel Pharmaceuticals, Inc.

About REZLIDHIA
INDICATION
REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME
Differentiation syndrome, which can be fatal, can occur with REZLIDHIA treatment. Symptoms may include dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain. If differentiation syndrome is suspected, withhold REZLIDHIA and initiate treatment with corticosteroids and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS
Differentiation Syndrome
REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence.

Hepatotoxicity
REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin.

Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity.

ADVERSE REACTIONS
The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis.

DRUG INTERACTIONS

Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers.
Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
LACTATION
Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose.

GERIATRIC USE
No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age.

HEPATIC IMPAIRMENT
In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome.

Click here for Full Prescribing Information, including Boxed WARNING.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

REZLIDHIA is a registered trademark of Rigel Pharmaceuticals, Inc.

On January 8, 2024 Replimune presented its corporate presentation (Presentation, Replimune, JAN 8, 2024, View Source [SID1234639106]).

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On January 8, 2024 Relay Therapeutics presented its corporate presentation (Presentation, Relay Therapeutics, JAN 8, 2024, View Source [SID1234639105]).

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Discover why more than 1,500 members use 1stOncology™ to excel in:

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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