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ANTICANCER AGENT “Remitoro® INTRAVENOUS DRIP INFUSION 300?g”(DENILEUKIN DIFTITOX (GENETIC RECOMBINANT)) APPROVED IN JAPAN FOR PERIPHERAL T-CELL LYMPHOMA AND CUTANEOUS T-CELL LYMPHOMA

On March 23, 2021 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has obtained manufacturing and marketing approval for the anticancer agent "Remitoro for Intravenous Drip Infusion 300μg" (denileukin diftitox (genetic recombinant)) with the indications of relapsed or refractory Peripheral T-cell Lymphoma (PTCL) and relapsed or refractory Cutaneous T-cell Lymphoma (CTCL), in Japan (Press release, Eisai, MAR 23, 2021, View Source [SID1234577000]). This agent was evaluated by the Ministry of Health, Labour and Welfare (MHLW) as a drug with high medical need at the "Study Group for Unapproved Drugs/Off-Label Drugs for High Medical Need". Hence, Eisai has been working on the development of the agent thereof in Japan, and applied for manufacturing and marketing approval in March 2020, based primarily on data from a Phase II clinical study (Study 205).

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Study 205 is a multicenter, open-label, single-arm Phase II clinical study, conducted in Japan to evaluate the efficacy and safety of the agent in patients with relapsed or refractory PTCL or CTCL.

This study achieved the primary endpoint target and exceeded a prespecified tumor response threshold with statistical significance: the objective response rate (ORR) of PTCL and CTCL patients in total (n=36) was 36.1% (95% confidence interval (CI): 20.8-53.8). The ORRs of each subtype were 41.2% (95%CI: 18.4-67.1) for PTCL (n=17) and 31.6% (95% CI: 12.6-56.6) for CTCL (n=19).

The five most frequent treatment-emergent adverse events observed in this study were increased aspartate aminotransferase (AST) (89.2%), increased alanine aminotransferase (ALT) (86.5%), hypoalbuminaemia (70.3%), lymphopenia (70.3%), and pyrexia (51.4%).

Eisai will conduct a post-marketing special use results survey (all-case surveillance) in all patients who are administered the agent until a pre-determined number of patients has been reached in accordance with an approval condition imposed by the MHLW.

The agent is a fusion protein consisting of interleukin-2 (IL-2) and partial sequence of diphtheria toxin, and specifically binds to the IL-2 receptor on the surface of tumoral lymphocytes. The antitumor effect of denileukin diftitox depends on the intracellular delivery of diphtheria toxin fragment which inhibits protein synthesis and induces cell death. Eisai retains exclusive development and marketing rights for the agent in Japan and Asia.

Eisai aims to make continuous efforts to meet the diversified needs of and increase the benefits provided to patients with cancer, their families, and healthcare professionals, by delivering "Remitoro" as a new treatment option for relapsed or refractory PTCL and relapsed or refractory CTCL in Japan.

1. About Remitoro for Intravenous Drip Infusion 300μg (Denileukin Diftitox (Genetic Recombinant))

This agent is a fusion protein consisting of interleukin-2 (IL-2) and partial sequence of diphtheria toxin. The antitumor effect of denileukin diftitox depends specific binding to the IL-2 receptor on the surface of tumoral lymphocytes followed by intracellular delivery and release of diphtheria toxin fragment which inhibits protein synthesis and induces cell death.

Eisai retains exclusive development and marketing rights for the agent in Japan and Asia, and in other regions, Dr. Reddy’s Laboratories Ltd. has development and marketing rights.

2. About Phase II Clinical Study (Study 205)

Study 205 is a multicenter, open-label, single-arm phase II clinical study evaluating the efficacy and safety of denileukin diftitox (genetic recombinant) conducted in Japan for patients with relapsed or refractory Peripheral T-cell Lymphoma (PTCL) or Cutaneous T-cell Lymphoma (CTCL). The patients who participated in this study received a final histopathological definitive diagnosis by the Central Committee for Pathological Diagnosis, which is independent of the clinical study site. The histopathological subtypes of participants consisted of 17 patients with PTCL, 19 patients with CTCL, and 1 patient with other malignant lymphoma. The efficacy of the agent was evaluated in 36 patients with PTCL or CTCL, and the safety was evaluated in 37 patients. The agent was administered by intravenous drip infusion over 60 minutes at a dose of 9μg / kg / day for five consecutive days from day 1 to day 5 to complete a cycle, with one cycle every three weeks and a maximum of up to 8 cycles conducted. In this study, the primary endpoint was objective response rate, and the efficacy of the agent was evaluated on the basis that the lower limit of the confidence interval (CI) was above a predetermined threshold.

3. About Peripheral T-cell Lymphoma (PTCL)

PTCL is a type of T-cell non-Hodgkin’s lymphoma that is classified as an intermediate-grade lymphoma. PTCL is often detected in advanced stages, and has symptoms such as swelling and lumps in the lymph nodes, fever, heavy night sweats, and weight loss. Among PTCLs, Anaplastic Lymphoma Kinase (ALK)-positive anaplastic large cell lymphoma, which occurs in the 20s and 30s, has a favorable prognosis and is curable. However, other types of PTCL often occur around the age of 60, and may have a poor prognosis or be difficult to treat. Therefore, PTCL is still a disease with extremely high-unmet medical need. It is estimated that the number of patients with PTCL in Japan is less than 6,000.1

4. About Cutaneous T-cell Lymphoma (CTCL)

CTCL is a type of non-Hodgkin’s lymphoma of primary cutaneous disease with various other manifestations in additional sites like lymph nodes and peripheral blood. In CTCL, some of the T cells (a type of lymphocyte involved in the immune system) become cancerous, causing skin lesions and reducing the patient’s QOL (Quality of Life) due to pain and pruritus. CTCL is generally a low-grade lymphoma, with initial patch and plaque skin lesions, but it progresses slowly and advances to the tumor stage over several years to over a dozen years. CTCL is still a disease with extremely high unmet medical need because it has a high malignancy when it reaches the tumor stage and has a poor prognosis. It is estimated that the number of patients with CTCL in Japan is less than 4,000.1

5. About Study Group for Unapproved Drugs/Off-Label Drugs for High Medical Need

The Study Group was set up within the Ministry of Health, Labour and Welfare with the purpose of contributing to enhancing the development of drugs and indications that have not been approved in Japan (unapproved drugs/off-label drugs) by pharmaceutical companies. In addition to evaluating the medical needs of unapproved drugs/off-label drugs, their responsibilities include evaluating the applicability of the drug to an Application with Public Knowledge, and the adequacy of additional clinical studies that need to be conducted for filing applications for approval, and so on.

1. Vital Statistics/Patient Survey in 2017 (Statistics and Information Department, Minister’s Secretariat, Ministry of Health, Labour and Welfare, Japan.) (available in Japanese only)

Pulmatrix Reports 2020 Financial Results and Provides Business Update

On March 23, 2021 Pulmatrix, Inc. (NASDAQ: PULM), a clinical stage biopharmaceutical company developing innovative inhaled therapies to address serious pulmonary and non-pulmonary disease using its patented iSPERSE technology, reported its Q4 and full year 2020 financial results and provides a business update (Press release, Pulmatrix, MAR 23, 2021, View Source [SID1234576998]).

"In recent months, we have made important progress advancing iSPERSE enabled programs that both strengthen our foundation in respiratory indications and expand the reach of our platform to lung cancer and acute migraine," said Ted Raad, Chief Executive Officer of Pulmatrix. "Our strengthened balance sheet fully funds our operations through key data milestones across our ongoing and planned studies including the PUR1800 Phase 1b study, the PUR3100 Phase 1 / Phase 2 study and Pulmazole Phase 2b study. We look forward to a milestone rich 2021 which includes toxicology and clinical data packages from ongoing PUR1800 studies, potential license option execution from Johnson & Johnson, and continued execution as we advance therapies to address significant unmet need."

Q4 and Recent Highlights:

PUR1800

Initiated the Phase 1b clinical study of PUR1800, dosing 4 of 15 patients to date. Study endpoints include safety, tolerability and exploratory biomarkers to demonstrate target engagement and anti-inflammatory effect. Ph1b top-line data is expected in Q4 2021, shortly after data from 6 and 9-month toxicology studies.
Completion of the PUR1800 Phase 1b will trigger a $2M milestone payment as part of the kinase inhibitor licensing and development agreement with the Lung Cancer Initiative (LCI) at Johnson & Johnson*, which was previously on January 2, 2020.
Pulmazole

Successfully completed a Type C Meeting with the U.S. FDA for the further clinical development of Pulmazole.
Based on feedback from the Type C Meeting, and in accordance with our collaboration with Cipla, Pulmatrix intends to initiate a Phase 2b clinical study of Pulmazole in allergic bronchopulmonary aspergillosis (ABPA) in Q1 2022, dependent on assessment of COVID-19 impact on patient safety and study operations.
PUR3100

Declared PUR3100 development candidate, a dry powder iSPERSE formulation of DHE for pulmonary delivery in acute migraine.
Completed dog PK study of PUR3100, demonstrated similar exposure kinetics to modelled kinetics from published data with MAP0004, the MAP Pharmaceuticals pMDI inhaled formulation of DHE.
Progressing IND-enabling studies with Phase 1/Phase 2 clinical study anticipated to begin Q1 2022.
Corporate:

Completed a registered direct offering with gross proceeds of $40 million extending the Company’s cash through data readouts across its development pipeline including PUR1800 Phase 1b, PUR3100 Phase 1 / Phase 2, and Pulmazole Phase 2b studies.
Financials

As of December 31, 2020, Pulmatrix had $31.7 million in cash and cash equivalents, compared to $23.4 million for the year ended December 31, 2019.

Revenue for 2020 was $12.6 million, compared to $7.9 million for 2019. The increase resulted from an increase in revenue recorded of $6.9 million as a result of the JJEI License Agreement and includes reimbursement of pass-through expenses, partially offset by a decrease in revenue recorded of $2.2 million as a result of the Cipla Agreement.

Research and development expense was $15.6 million in 2020 compared to $12.8 million in 2019. The increase year–over–year was primarily due to increased spending on manufacturing, clinical, and preclinical study costs of $4.4 million and $0.3 million, on the PUR1800 and PUR3100 programs, respectively, $1.1 million on employment costs in support of our programs, $0.6 million in allocated fixed expenses and lab services which were partially offset by a decrease of $3.6 million on the Phase 2 Pulmazole clinical trial costs.

General and administrative expense was $6.9 million for 2020 and $8.5 million for 2019. The decrease year-over-year was primarily due to decreased employment costs of $1.2 million because of lower share-based compensation expense and salary costs, $0.1 million in patent and legal expenses and $0.3 million of a milestone payment to the CFFT made in 2019.

Goodwill was not impaired in 2020 compared to a $7.3 million impairment charge in 2019.

Net loss for 2020 was $19.3 million. The net loss in 2020 was primarily attributable to Pulmazole project costs as we advanced our Phase 2 clinical study and PUR1800 manufacturing, preclinical, and clinical study costs for the upcoming Phase 1b clinical study.

Incyte Announces Approval of Pemazyre® (pemigatinib) in Japan for the Treatment of Patients with Unresectable Biliary Tract Cancer (BTC) with a Fibroblast Growth Factor Receptor 2 (FGFR2) Fusion Gene, Worsening After Cancer Chemotherapy

On March 23, 2021 Incyte (Nasdaq:INCY) reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Pemazyre (pemigatinib), a selective fibroblast growth factor receptor (FGFR) inhibitor, for the treatment of patients with unresectable biliary tract cancer (BTC) with a fibroblast growth factor receptor 2 (FGFR2) fusion gene1, worsening after cancer chemotherapy (Press release, Incyte, MAR 23, 2021, View Source [SID1234576994]).

"The MHLW approval of Pemazyre is an important milestone for the BTC community, and underscores our commitment to finding and delivering solutions for patients with significant unmet medical needs," said Lothar Finke, M.D., Ph.D., General Manager, Incyte Asia. "BTC is a rare and serious condition, and we are proud that with the support of the MHLW we will be able to bring a new targeted treatment to more patients around the world."

BTC is a rare cancer that forms in the bile duct. Cholangiocarcinoma, a subtype of BTC, is classified based on its origin: intrahepatic, which occurs in the bile duct inside the liver and extrahepatic, which occurs in the bile duct outside the liver. Patients with BTC are often diagnosed at a late or advanced stage when the prognosis is poor2,3. FGFR2 fusions or rearrangements, which occur almost exclusively in intrahepatic cholangiocarcinoma, are observed in a small percentage of Japanese patients with BTC4,5,6,7.

The approval is based on data from the FIGHT-202 study evaluating the safety and efficacy of pemigatinib in adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGF/FGFR status. In FIGHT-202 patients harboring FGFR2 fusions or rearrangements (Cohort A), Pemazyre monotherapy resulted in an overall response rate of 36% (primary endpoint), and median DOR of 7.49 months (secondary endpoint). The most frequent treatment-emergent adverse event (TEAE) were grade ≤2 hyperphosphatemia (58.2%). Other frequent TEAEs (all grades) observed in ≥30% of patients were alopecia, diarrhea, fatigue, dysgeusia, nausea, constipation, stomatitis, dry mouth and decreased appetite. The majority of these TEAEs were grade ≤2. The TEAE with grade ≥3 that occurred in ≥10% of patients was hypophosphatemia.

Previously, the MHLW granted Orphan Drug Designation for Pemazyre – a designation granted to investigational compounds intended to treat rare diseases that affect fewer than 50,000 people in Japan, and for which there is a high medical need8. Designated orphan drugs are eligible for priority review for marketing authorizations to ensure supply to clinical settings at the earliest opportunity8.

About FIGHT-202

The FIGHT-202 Phase 2, open-label, multicenter study (NCT02924376) is evaluating the safety and efficacy of pemigatinib – a selective fibroblast growth factor receptor (FGFR) 1, 2, 3 inhibitor – in adult (age ≥ 18 years) patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGF/FGFR status.

Patients were enrolled into one of three cohorts – Cohort A (FGFR2 fusions or rearrangements), Cohort B (other FGF/FGFR genetic alterations) or Cohort C (no FGF/FGFR genetic alterations). All patients received 13.5 mg pemigatinib orally once daily (QD) on a 21-day cycle (two weeks on/one week off) until radiological disease progression or unacceptable toxicity.

The primary endpoint of FIGHT-202 is overall response rate (ORR) in Cohort A, assessed by independent review per RECIST v1.1. Secondary endpoints include ORR; progression free survival (PFS), overall survival (OS), duration of response (DOR), disease control rate (DCR) and safety in all cohorts.

For more information about FIGHT-202, visit View Source

About FIGHT

The FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program includes ongoing Phase 2 and 3 studies investigating safety and efficacy of pemigatinib therapy across several FGFR-driven malignancies. Phase 2 monotherapy studies include FIGHT-202, as well as FIGHT-201 investigating pemigatinib in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 mutations or fusions/rearrangements; FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 fusions/rearrangements; FIGHT-207 in patients with previously treated, locally-advanced/metastatic or surgically unresectable solid tumor malignancies harboring activating FGFR mutations or fusions/rearrangements, irrespective of tumor type.

FIGHT-302 is a Phase 3 study investigating pemigatinib as a first-line treatment for patients with cholangiocarcinoma with FGFR2 fusions or rearrangements.

About Pemazyre (pemigatinib)

Pemazyre is a kinase inhibitor indicated in the United States for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test9. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Japan, Pemazyre is approved for the treatment of patients with unresectable biliary tract cancer (BTC) with a fibroblast growth factor receptor 2 (FGFR2) fusion gene, worsening after cancer chemotherapy.

Pemazyre is a potent, selective, oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations.

Pemazyre is marketed by Incyte in the United States and will be marketed by Incyte in Japan. Incyte has granted Innovent Biologics, Inc. rights to develop and commercialize pemigatinib in hematology and oncology in Mainland China, Hong Kong, Macau and Taiwan. Incyte has retained all other rights to develop and commercialize pemigatinib outside of the United States.

Additionally, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the conditional marketing authorization of pemigatinib for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy.

Pemazyre is a trademark of Incyte Corporation.

Dr Thomas Morris appointed as Chief Medical Officer

On March 23, 2021 Oxford Vacmedix, the UK-based biopharma company focused on the development of cancer vaccines reported the appointment of Dr. Thomas Morris BSc, MB BCh, LlM, MRCP FFPM as Chief Medical Officer (Press release, Oxford Vacmedix, MAR 23, 2021, View Source [SID1234576993]). Tom originally worked as a physician in the NHS before joining industry, including many years at Astra Zeneca where he led the global clinical development of several oncology compounds. He has been responsible for the design, implementation and subsequent analysis of many study protocols, including several first in man clinical trials. Tom has wide experience in scientific interactions and in negotiation with the US, European and Japanese regulatory agencies on clinical development plans pre-phase III.

William Finch, Chief Executive Officer of Oxford Vacmedix said;
"I am delighted to welcome Tom to the team at Oxford Vacmedix at this critical time, as move our lead cancer vaccine, OVM-200, into the clinic. His extensive experience in oncology and in clinical development will be invaluable for the next phase of the development of our vaccines as monotherapy and in combination with immune-oncology agents, to meet the needs of cancer patients."

Dr Morris qualified in Physiology and Medicine from the University of Wales in 1987 and went on to gain a master’s degree in Law from the University of Cardiff. He was awarded the Fellowship of the Faculty of Pharmaceutical Medicine from the Royal College of Physicians in 2003 and was appointed to the role of Registrar and Board Member of the Faculty in 2015. Tom also served as a member of the Faculty’s Coordination Committee and as a Speciality Adviser, responsible for overseeing training in pharmaceutical medicine, and was previously Chair of the Ethical Issues Committee and member of the Professional Standards Committee of the Faculty.

Tom Morris commented;
"I am very pleased to be joining Oxford Vacmedix to lead the clinical development of these novel cancer vaccines. The underlying ROP technology offers great hope to provide safe and effective therapies to help people with cancer live longer and better lives, and I look forward to making a positive contribution to the company."

Novartis announces positive result of phase III study with radioligand therapy 177Lu-PSMA-617 in patients with advanced prostate cancer

On March 23, 2021 Novartis reported the first interpretable results of the Phase III VISION study evaluating the efficacy and safety of 177Lu-PSMA-617, a targeted radioligand therapy in patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) compared to best standard of care alone (Press release, Novartis, MAR 23, 2021, View Source [SID1234576992]). The trial met both primary endpoints of overall survival and radiographic progression-free survival1, helping to move closer the ambition of becoming the targeted treatment for >80% of patients with advanced prostate cancer. The safety profile was consistent with data reported in previous clinical studies1. Results from the VISION trial will be presented at an upcoming medical meeting and included in US and EU regulatory submissions.

"Patients with metastatic castration-resistant prostate cancer have a less than 1 in 6 chance of surviving 5 years2 and need new treatment options. These groundbreaking data confirm our belief in the potential of 177Lu-PSMA-617 to reimagine outcomes for these patients through phenotypic precision medicine. We intend to submit these data to regulatory authorities as soon as possible," said John Tsai, Head of Global Drug Development and Chief Medical Officer for Novartis. "We would like to thank the patients who volunteered to participate in this study as well as the clinical teams at each of the trial sites. We would not be able to realize our commitment to reimagining medicine without the partnership of patients and their families."

Radioligand therapy combines a targeting compound that binds to markers expressed by tumors and a radioactive isotope, causing DNA damage that inhibits tumor growth and replication. This therapeutic approach enables targeted delivery of radiation to the tumor, while limiting damage to the surrounding normal tissue. Novartis has established global expertise and specialized supply chain and manufacturing capabilities across its network of four radioligand therapy production sites, and is further increasing capacity to ensure delivery of radioligand therapies like 177Lu-PSMA-617 to patients in need.

Novartis is the only pharmaceutical company which is pursuing four different cancer treatment platforms. These include radioligand therapy, cell and gene therapy, and targeted therapy and immunotherapy, with an opportunity to combine these platforms for the best outcomes for each cancer patient.

About Advanced Prostate Cancer
Prostate cancer is a form of cancer that develops in the prostate gland, a small walnut shaped gland in the pelvis of men. In castration resistant prostate cancer (CRPC), the tumor shows signs of growth, such as rising Prostate Specific Antigen (PSA) levels, despite the use of hormone treatments that lower testosterone3. In metastatic CRPC (mCRPC), the tumor spreads to other parts of the body, such as neighboring organs or bones and remains unresponsive to hormone treatment4. The five-year survival rate for patients with mCRPC is approximately 15%2.

About Phenotypic Precision Medicine in Advanced Prostate Cancer
Despite advances in prostate cancer care, there is a high unmet need for new targeted treatment options to improve outcomes for patients with metastatic castration resistant prostate cancer. More than 80% of prostate cancer tumors highly express a phenotypic biomarker5 called Prostate Specific Membrane Antigen (PSMA)4,6-9, making it a promising diagnostic (through positron emission tomography (PET) scan imaging) and therapeutic target for radioligand therapy6.

About 177Lu-PSMA-617
177Lu-PSMA-617 is an investigational PSMA-targeted radioligand therapy for metastatic castration-resistant prostate cancer. It is a type of precision cancer treatment combining a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle)10-12. After administration into the bloodstream, 177Lu-PSMA-617 binds to prostate cancer cells that express PSMA13, a transmembrane protein, with high tumor-to-normal tissue uptake10,14,15. Once bound, emissions from the radioisotope damage tumor cells, disrupting their ability to replicate and/or triggering cell death. The radiation from the radioisotope works over very short distances to limit damage to surrounding cells14,16.

About VISION
VISION is an international, prospective, randomized, open-label, multicenter, phase III study to assess the efficacy and safety of 177Lu-PSMA-617 (7.4 GBq administered by i.v. infusion every 6 weeks for a maximum of 6 cycles) plus investigator-chosen best standard of care in the investigational arm, versus best standard of care in the control arm17. Patients with PSMA PET-scan positive mCRPC, and progression after prior taxane and androgen receptor-directed therapy (ARDT), were randomized in a 2:1 ratio in favor of the investigational arm. The alternate primary endpoints were rPFS and OS. The study enrolled 831 patients1.