On December 13, 2019 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, will present updated interim results from a Phase II clinical trial of Puma’s drug neratinib at the 2019 San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas (Press release, Puma Biotechnology, DEC 13, 2019, View Source [SID1234552359]). The presentation entitled, "Effect of prophylaxis or neratinib dose escalation on neratinib-associated diarrhea and tolerability in patients with HER2-positive early-stage breast cancer: Phase II CONTROL trial," will be displayed at a poster session on December 13 at 5:00 p.m. CST. A full copy of the poster is available on the Puma Biotechnology website.

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Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy and is marketed in the United States as NERLYNX (neratinib) tablets.

The main adverse event seen to date in clinical trials of neratinib is diarrhea and, more specifically, grade 3 diarrhea. In the Phase III ExteNET trial of neratinib as extended adjuvant treatment of HER2-positive early stage breast cancer that has previously been treated with adjuvant Herceptin, prophylactic use of anti-diarrheal medications was not mandatory. In the trial, 95.4% of the patients experienced all grade diarrhea and 39.8% of the patients experienced grade 3 or higher diarrhea (there was one event of grade 4 diarrhea). The median cumulative duration of grade 3 diarrhea in the ExteNET trial was 5 days and 16.8% of patients who received neratinib in the ExteNET trial discontinued the drug due to diarrhea.

The CONTROL trial is an international, open-label, Phase II study investigating the use of antidiarrheal prophylaxis or dose escalation in the reduction of neratinib-associated diarrhea that has a primary endpoint of the incidence of grade 3 diarrhea.

In the CONTROL trial, patients with HER2-positive early stage breast cancer who had completed trastuzumab-based adjuvant therapy received neratinib daily for a period of one year. The trial initially tested high dose loperamide prophylaxis given for the first 2 cycles (56 days) of treatment (12 mg on days 1-14, 8 mg on days 15-56 and as needed thereafter). The CONTROL trial was then expanded to include four additional cohorts. One cohort received the combination of loperamide and budesonide, the second cohort received the combination of loperamide plus colestipol, the third cohort received colestipol plus loperamide as needed and the fourth cohort did not use any antidiarrheal drugs as mandatory prophylaxis but instead used a dose escalation during the first month of neratinib treatment. Budesonide is a locally acting corticosteroid that Puma believes targets the inflammation identified in a preclinical model of neratinib-induced diarrhea and colestipol is a bile acid sequestrant that Puma believes targets potential bile acid malabsorption that could result from such inflammation. The dose escalation involved treating with neratinib at 120 mg per day for the first week, 160 mg per week for the second week and 240 mg per week starting at week 3 and until the end of treatment.

The interim analysis of the CONTROL trial presented in the poster included a total of 137 patients who received neratinib plus loperamide prophylaxis, 64 patients who received neratinib plus loperamide prophylaxis for 2 cycles and budesonide for 1 cycle, 136 patients who received neratinib plus loperamide prophylaxis for 1 cycle and colestipol for 1 cycle, 104 patients who received colestipol for 1 cycle and loperamide as needed and 60 patients who received the dose escalation regimen of neratinib.

The results of the trial showed that the incidence of grade 3 diarrhea for the 137 patients who received the loperamide prophylaxis was 31% and that for the 137 patients in this cohort, 20% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 3 days.

For the 64 patients who received the combination of loperamide plus budesonide, the results of the trial showed that the incidence of grade 3 diarrhea was 28% and that for the 64 patients in this cohort, 11% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 2.5 days.

For the 136 patients who received the combination of loperamide plus colestipol, the results of the trial showed that the incidence of grade 3 diarrhea was 21% and that for the 136 patients in this cohort, 4% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 3.5 days.

For the 104 patients who received colestipol and loperamide as needed, the results of the trial showed that the incidence of grade 3 diarrhea was 34% and that for the 104 patients in this cohort, 8% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 3 days.

For the 60 patients who received no antidiarrheal drugs as mandatory prophylaxis and dose escalation of neratinib in the first month, the results of the trial showed that the incidence of grade 3 diarrhea was 15% and that for the 60 patients in this cohort, 3% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 2 days.

Further information is provided in Table 1 below:

Each patient was counted only once in the highest grade category.

No Grade 4 events reported in the CONTROL study.

Carlos H. Barcenas, MD, MS, Associate Professor in the Department of Breast Medical Oncology of The University of Texas MD Anderson Cancer Center, said, "We are pleased to see the maturation of the data supporting observations of a reduction in incidence, severity and duration of neratinib-associated diarrhea with loperamide prophylaxis, loperamide plus budesonide prophylaxis or the loperamide plus colestipol prophylaxis. Along with the continued reduction in the incidence and severity of grade 3 diarrhea with neratinib, diarrhea appears to be early onset, acute, self-limiting and manageable. Not only does the addition of budesonide or colestipol to loperamide prophylaxis appear to greatly improve the tolerability of neratinib, the dose escalation regimen appears as another promising option since there is no mandatory prophylaxis."

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are pleased to note that the dose-escalation cohort of our CONTROL trial continues to show a marked improvement in the incidence of grade 3 diarrhea and related discontinuation of therapy. We remain committed to improving the tolerability of neratinib in early stage breast cancer patients."

About HER2-Positive Breast Cancer

Approximately 20% to 25% of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

IMPORTANT SAFETY INFORMATION

NERLYNX (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early-stage HER2 overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

Diarrhea: Aggressively manage diarrhea occurring despite recommended prophylaxis with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥ 2 diarrhea that occurs after maximal dose reduction.
Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold NERLYNX in patients experiencing Grade 3 liver abnormalities and permanently discontinue NERLYNX in patients experiencing Grade 4 liver abnormalities.
Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
ADVERSE REACTIONS: The most common adverse reactions (≥ 5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight decreased and urinary tract infection.

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) and www.NERLYNX.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS:

Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors. When patients require gastric acid reducing agents, use an H2-receptor antagonist or antacid. Separate NERLYNX by at least 3 hours with antacids. Separate NERLYNX by at least 2 hours before or 10 hours after H2-receptor antagonists.
Strong or moderate CYP3A4 inhibitors: Avoid concomitant use.
Strong or moderate CYP3A4 inducers: Avoid concomitant use.
P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates when used concomitantly with NERLYNX.
USE IN SPECIFIC POPULATIONS:

Lactation: Advise women not to breastfeed.
Please see Full Prescribing Information for additional safety information.

The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given orally once daily with food, continuously for one year. Antidiarrheal prophylaxis should be initiated with the first dose of NERLYNX and continued during the first 2 months (56 days) of treatment and as needed thereafter.

To help ensure patients have access to NERLYNX, Puma has implemented the Puma Patient Lynx support program to assist patients and healthcare providers with reimbursement support and referrals to resources that can help with financial assistance. More information on the Puma Patient Lynx program can be found at www.NERLYNX.com or 1-855-816-5421.

On December 13, 2019 PDL BioPharma, Inc. ("PDL" or the "Company") (Nasdaq: PDLI) reported that it has entered into separate, privately negotiated exchange agreements pursuant to which it will exchange $119.3 million in aggregate principal amount of its outstanding 2.75% Convertible Senior Notes due in December 2021 (the "2021 Notes") and in December 2024 (the "2024 Notes") for (i) cash in an aggregate amount of $98.0 million, such cash amount to include $139,900 of accrued and unpaid interest on the exchanged notes up to, but excluding, the settlement dates, and (ii) an aggregate of 13.4 million shares of its common stock, par value $0.01 per share ("Common Stock") (Press release, PDL BioPharma, DEC 13, 2019, View Source [SID1234552358]).

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"We believe that the exchange of these notes is an important first step in executing on the strategy announced earlier this week to monetize our assets and return value to our shareholders," said Dominique Monnet, president and CEO of PDL. "Reducing the aggregate $150 million of convertible notes outstanding by approximately 80% will enable us to operate with broader flexibility and on more favorable financial terms by significantly lessening the impact of provisions of the Convertible Note Indentures governing such activities. The privately negotiated exchanges were executed under the note and share repurchase program authorized by our board and announced last Monday."

The 2021 Notes will be exchanged for an aggregate $39.9 million of cash and 3.5 million shares of Common Stock. The 2024 Notes will be exchanged for an aggregate $58.1 million of cash and 9.9 million shares of Common Stock. Upon consummation of the closing, approximately $19.2 million and $11.5 million aggregate principal amount of the 2021 Notes and 2024 Notes, respectively, will remain outstanding.

In connection with the exchange transactions, PDL and Royal Bank of Canada (the "Counterparty" or "RBC") entered into an agreement to terminate a portion of the capped call agreements previously entered into for the 2021 Notes and 2024 Notes in notional amounts corresponding to the amounts of notes exchanged. The Company will receive cash proceeds from the Counterparty of $6.7 million as a result of the partial unwinding of the capped call agreements. The capped call transactions remain in effect for the 2021 Notes and 2024 Notes that remain outstanding.

In connection with the partial unwinding of the capped call agreements, the Company has entered into an agreement with RBC to purchase 3.2 million shares of PDL Common Stock previously acquired by RBC (and or its affiliates) to hedge the capped calls. The Common Stock was acquired by PDL at the closing price of PDL’s Common Stock on December 12, 2019.

The transactions are subject to customary closing conditions and are expected to close on or before Tuesday, December 17, 2019. The shares of Common Stock will be issued in reliance upon the exemption from registration under Section 3(a)(9) of the Securities Act of 1933, as amended.

BofA Securities acted as financial advisor to PDL in connection with the transactions.

On December 13, 2019 Innate Pharma SA (Euronext Paris: IPH – ISIN: FR0010331421; Nasdaq: IPHA) ("Innate" or the "Company") reported an update regarding its TELLOMAK Phase II trial evaluating the efficacy and safety of lacutamab (IPH4102, a potentially first-in-class anti-KIR3DL2 antibody) (Press release, Innate Pharma, DEC 13, 2019, View Source [SID1234552357]). The Company will take the following actions based on ongoing discussions with regulatory authorities regarding a quality issue related to the chemistry, manufacturing and controls (CMC) process:

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Lacutamab will not be administered to new patients in the TELLOMAK trial until additional feedback is received from the respective regulatory agencies overseeing our clinical trial.
Until further notice, the Company will continue to treat patients who are currently enrolled in the multi-center trial, except in Italy where the clinical trial has been suspended due to the feedback from Italian regulatory authorities.
This decision is related to issues with the Company’s manufacturing subcontractor, Rentschler Fill Solutions GmbH or "RFS" (now known as Impletio Wirkstoffabfüllung GmbH). RFS has recently withdrawn the Certificate of Conformity of batches they have produced, including the lacutamab batch currently used in the TELLOMAK trial. RFS was granted a Good Manufacturing Practice (GMP) certificate by the Austrian regulatory agency in August 2018 and further confirmed in October 2019. In parallel, RFS filed for bankruptcy.

The Company’s utmost priority is to ensure patient safety, and no new safety issues have been reported to date in the TELLOMAK trial. An extensive internal and third-party analysis concluded that there was no element that would affect the CMC quality of the product.

Innate will provide an update once it has received additional feedback from the relevant regulatory agencies. In parallel, the Company is working on resolution of the quality issues related to the CMC matter.

About Lacutamab:

Lacutamab (formerly IPH4102) is a potentially first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody, designed for treatment of CTCL, an orphan disease. This group of rare cutaneous lymphomas of T lymphocytes has a poor prognosis with few therapeutic options at advanced stages. KIR3DL2 is an inhibitory receptor of the KIR family, expressed by approximately 65% of patients across all CTCL subtypes and expressed by up to 85% of them with certain aggressive CTCL subtypes, in particular, Sézary syndrome. It has a restricted expression on normal tissues.

Lacutamab was granted orphan drug status in the European Union and in the United States for the treatment of CTCL. In January 2019, the US Food and Drug Administration (FDA) granted Innate Pharma Fast Track designation for lacutamab for the treatment of adult patients with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies.

About TELLOMAK Trial:

TELLOMAK is a global, open-label, multi-cohort Phase II clinical trial conducted in the United States and Europe. In this clinical trial, lacutamab is being evaluated alone and in combination with chemotherapy in patients with advanced TCL. TELLOMAK is expected to recruit up to 250 patients, with lacutamab evaluated:

As a single agent in approximately 60 patients with Sézary syndrome who have received at least two prior treatments, including mogamulizumab,
As a single agent in approximately 90 patients with MF who have received at least two prior treatments, and
In combination with standard chemotherapy (gemcitabine and oxaliplatin) in approximately 100 patients with PTCL who have received at least one prior treatment.
In patients with MF and PTCL, the study is designed to evaluate the benefit of lacutamab according to KIR3DL2 expression. The study comprises two cohorts for each of the two indications, testing lacutamab in KIR3DL2 expressing and non-expressing patients. These cohorts follow a Simon 2-stage design that will terminate if treatment is considered futile. The Sézary syndrome arm of the study could enable the registration of lacutamab in this indication.

The primary endpoint of the trial is objective response rate. Key secondary measures include incidence of treatment emergent adverse events, quality of life, overall response rate, progression-free survival and overall survival.

On December 13, 2019 Helix BioPharma Corp. (TSX, FSE: "HBP"), a an immuno-oncology company developing drug candidates for the prevention and treatment of cancer, reported its financial results for the first quarter of fiscal 2020 ending October 31, 2019 (Press release, Helix BioPharma, DEC 13, 2019, View Source [SID1234552356]).

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OVERVIEW

The Company recorded a net loss and total comprehensive loss, including non-controlling interest of $2,211,000 ($0.02 loss per common share) and $1,379,000 ($0.01 loss per common share) for the three-month periods ended October 31, 2019 and 2018, respectively. Fluctuations in net loss and total comprehensive loss is mainly the result of cash reserves available to be deployed on ongoing research and development activities and operating, general and administration expenses.

The Company experienced a working capital deficiency for several quarters until recently when on August 21, 2019 the Company closed a private placement financing for gross proceeds of $7,000,005 which included the disposition of a 25% stake in the Company’s Polish subsidiary, Helix Immuno-Oncology S.A. As previously disclosed, the Company intends to fully divest its remaining interest in its Polish subsidiary to raise additional capital to fund the Company’s clinical development programs while retaining licensing agreements for future royalties and milestones payments.

In addition, the Company has been in discussions with various capital market firms, both in the U.S. and Canada, with the goal of raising sufficient capital to qualify the Company for a listing on a U.S. stock exchange such as NASDAQ in order to further advance the Company’s clinical development programs.

On December 11, 2019 the Company announced that patient enrollment and screening had commenced on its Phase Ib/II clinical study in the U.S. The study is entitled "A Phase Ib/II Study of the Microenvironment Modifier L-DOS47 plus Doxorubicin for the Treatment of Patients with Previously Treated Advanced Pancreatic Cancer". The Phase Ib portion of the study involves three dose escalating cohorts enrolling a total of nine (9) patients. The Phase II portion of the study will enroll an additional eleven (11) patients depending on meeting safety and efficacy criteria.

Research and development Research and development costs for the three-month periods ended October 31, 2019 and 2018 totalled $1,511,000 and $1,014,000, respectively. The following table outlines research and development costs expensed for the Company’s significant research and development projects for the three-month periods ending October 31: 2019 2018

L-DOS47 research and development expenses for the three-month periods ended October 31, 2019 and 2018 totalled $1,211,000 and $861,000, respectively.

L-DOS47 research and development expenditures relate primarily to the Company’s LDOS001 Phase I clinical study in the U.S., the LDOS002 European Phase I/II clinical study in Poland, the LDOS003 Phase II clinical study in Poland and the Ukraine and the Company’s newly approved Phase Ib/II clinical study in the U.S. (LDOS006).

As a result of closing a private placement for gross proceeds of $7,000,005 on August 21, 2019, the Company committed to various expenditures related to its L-DOS47 clinical development program, specifically as it relates to the Company’s’ recently approved IND clinical study for previously treated advanced pancreatic cancer (LDOS006). The Company expects to enrol the first patient by the end of the calendar year 2019. In the meantime, the Company’s other NSCLC studies (LDOS001 and LDOS002) are both in late stages of development within their respective clinical phases and the Company is working on finalizing the data for reporting.

V-DOS47 research and development expenses for the three-month periods ended October 31, 2019 and 2018 totalled $111,000 and $130,000, respectively. The Company’s wholly owned subsidiary in Poland has a grant funding agreement with the Polish National Centre for Research and Development ("PNCRD") for research and development expenditures associated with V-DOS47. The Company’s subsidiary received $27,000 and $135,000 in the three-month periods ended October 31, 2019 and 2018, respectively, from the PNCRD.

Trademark and patent related expenses for the three-month periods ended October 31, 2018 and 2017 totalled $153,000 and $25,000, respectively. The Company continues to ensure it adequately protects its intellectual property.

Operating, general and administration Operating, general and administration expenses for the three-month periods ended October 31, 2019 and 2018 totalled $709,000 and $373,000, respectively. The increase in operating, general and administration expenses mainly reflects higher third-party advisor expenditures such as legal & accounting, investor & media relations, investment banking services and stock-based compensation from options granted over their vesting period. In addition, the much lower operating expenditures for the three-month period ending October 31, 2018 was also the result of cost cutting initiatives.

LIQUIDITY AND CAPITAL RESOURCES
The Company reported a consolidated net loss and total comprehensive loss including non-controlling interest of $2,211,000 for the three-month period ended October 31, 2019 (October 31, 2018-$1,379,000). As at October 31, 2019 the Company has working capital of $430,000, shareholders’ equity of $666,000 and a deficit of $173,707,000. As at July 31, 2019 the Company had a working capital deficiency of $3,534,000, shareholders’ deficiency of $3,281,000 and a deficit of $171,531,000.

The Company experienced a working capital deficiency for several fiscal quarters, until recently when on August 21, 2019 the Company closed a private placement financing for gross proceeds of $7,000,005 which included a disposition of a 25% stake in the Company’s Polish subsidiary, Helix Immuno-Immunology S.A. As previously disclosed, the Company intends to fully divest its remaining interest in its Polish subsidiary to raise additional capital to fund the Company’s clinical development programs for future royalties and milestone payments.

In addition, the Company has been in discussions with various capital market firms, both in the U.S. and Canada, with the goal of raising sufficient capital to qualify the Company for a listing on a U.S. stock exchange such as NASDAQ in order to further advance the Company’s clinical development programs.

The Company’s cash reserves of $1,650,000 as at October 31, 2019 in addition to the subsequent private placement the Company closed on August 21, 2019 are insufficient to meet anticipated cash needs for working capital and capital expenditures through the next twelve months, and nor are they sufficient to see planned research and development initiatives through to completion. Though the funds raised have assisted the Company in dealing with its working capital deficiency, additional funds are required to advance the Company’s clinical and preclinical programs and deal with working capital requirements To the extent that the Company does not believe it has sufficient liquidity to meet its current obligations, management considers securing additional funds, primarily through the issuance of equity securities of the Company, to be critical for its development needs. 3

The Company’s Consolidated Statement of Net Loss and Comprehensive Loss and Consolidated Statement of Cash Flow for the three-month periods ended October 31, 2019 and 2018 are summarized below: The Company’s condensed unaudited interim consolidated financial statements and management’s discussion and analysis will be filed under the Company’s profile on SEDAR at www.sedar.com, as well as on the Company’s website.

On December 13, 2019 Genmab A/S (Nasdaq: GMAB) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending broadening the existing marketing authorization for DARZALEX (daratumumab) in the European Union (Press release, Genmab, DEC 13, 2019, View Source [SID1234552354]). The recommendation is for the use of DARZALEX in in combination with bortezomib, thalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT).

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"We are very pleased with this positive opinion from the CHMP as, if approved, the combination of DARZALEX plus bortezomib, thalidomide and dexamethasone would be the first DARZALEX containing regimen that would be a potential treatment option for newly diagnosed patients with multiple myeloma in Europe who are eligible for ASCT," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The Type II variation application was submitted to the EMA by Janssen Pharmaceutica NV in March 2019 and was based on the Phase III CASSIOPEIA (MMY3006) study sponsored by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen R&D, LLC. Data from this study was published in The Lancet and presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

About the CASSIOPEIA (MMY3006) study
This Phase III study is a randomized, open-label, multicenter study, run by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen R&D, LLC, including 1,085 newly diagnosed subjects with previously untreated symptomatic multiple myeloma who are eligible for high dose chemotherapy and stem cell transplant. In the first part of the study, patients were randomized to receive induction and consolidation treatment with daratumumab combined with bortezomib, thalidomide (an immunomodulatory agent) and dexamethasone (a corticosteroid) or treatment with bortezomib, thalidomide and dexamethasone alone. The primary endpoint is the proportion of patients that achieve a stringent Complete Response (sCR). In the second part of the study, patients that achieved a response will undergo a second randomization to either receive maintenance treatment of daratumumab 16 mg/kg every 8 weeks for up to 2 years versus no further treatment (observation). The primary endpoint of this part of the study is progression free survival (PFS).

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Approximately 16,830 new patients were expected to be diagnosed with multiple myeloma and approximately 10,480 people were expected to die from the disease in the Western Europe in 2018.2 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.3 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.4

About DARZALEX(daratumumab)
DARZALEX (daratumumab) intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.5 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX intravenous infusion is indicated for the treatment of adult patients in Europe: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy6. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S. In Japan, DARZALEX intravenous infusion is approved for the treatment of adult patients: in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United States, Europe and Japan. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).5,6,7,8,9,10

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis, NKT-cell lymphoma and B-cell and T-cell ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.