On September 15, 2019 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported updated interim efficacy and safety data from the ongoing pivotal Phase 2 study, HORIZON, at the 17th International Myeloma Workshop (IMW) meeting in Boston, Massachusetts, USA (Press release, Oncopeptides, SEP 15, 2019, View Source [SID1234539502]). The data focused on patients with extramedullary disease (EMD) and was presented in an oral presentation by Professor Paul G. Richardson. Oncopeptides will host a conference call to review this data on Monday, September 16, 2019, at. 08.30 (CET).

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The results presented at IMW 2019 by Professor Paul G Richardson in the plenary session "Late Breaking Abstracts" under the title: Activity of Melflufen in RRMM Patients with Extramedullary Disease in the Phase 2 Study (OP-106 HORIZON) – Promising Results in a High-Risk Population, are based on a data cut in the HORIZON study dated July 30, 2019 when 136 patients were treated compared to previously reported data including 121 patients. Based on literature, HORIZON represents the largest clinical cohort to date of myeloma patients with extra medullary disease (EMD).

Relapsed-refractory multiple myeloma (RRMM) patients with extramedullary disease (EMD) is a very difficult to treat patient population. In recent single-agent studies (with or without steroids) including RRMM patients with EMD have shown overall response rates (ORR) between 0 – 17%. Only daratumumab has shown any relevant clinical activity with a response rate of 17% in daratumumab naïve myeloma patients with EMD.

In the HORIZON study, an overall response rate of 23% was achieved with treatment with melflfufen and dexamethasone in RRMM patients with EMD. These patients were mainly penta refractory (had undergone at least five prior treatments and were resistant to at least one proteasome inhibitor, one IMiD, and anti-CD38 treatment). The EMD patients who responded to the treatment had a median survival (OS) of 18.5 months compared to a median survival of 5.1 months for the EMD patients who did not respond to treatment. The difference observed suggests a clear clinical benefit for these patients.

Professor Paul G Richardson comments
"We are experiencing a significant increase in the number of relapsed and refractory myeloma patients with extramedullary disease and without effective treatment options. The observation in the HORIZON trial, that melflufen shows activity in these patients and may impact favorably on survival outcome, is very encouraging.

"In my view, given the relative lack of therapeutic alternatives for these patients, moving rapidly into melflufen-based combination strategies in patients with extramedullary disease, as well as exploring earlier lines of therapy, should be the next priority", said Professor Paul G Richardson, Professor of Medicine at Harvard Medical School and Clinical Program Leader, Director of Clinical Research at the Jerome Lipper Multiple Myeloma Center Dana-Farber Cancer Institute in Boston, Massachusetts, USA.

Overall Conclusions From the Presentation

As of July 30, 2019, 136 patients had been treated in HORIZON with melflufen and dexamethasone. 44 out of the 136 patients had confirmed EMD diagnosis at baseline
91% of EMD patients were triple-class refractory and 73% penta refractory
Similar ORR in non-EMD and EMD patients with an ORR of 27% and 23% respectively
Response rates in EMD patients was seemingly higher than historical studies
Median OS was 5.8 months for patients with EMD and 11.6 months for patients without EMD
Median OS in EMD responders and non-responders was 18.5 months and 5.1 months, respectively
Median OS in non-EMD responders and non-responders was 17.2 months and 8.5 months, respectively
The treatment was generally well tolerated, with manageable toxicity with a low overall incidence of nonhematologic Adverse Events (AE) including infections; no treatment-related deaths
The full presentation from IMW is available on the company’s website under:
www.oncopeptides.com / Investors&media / Presentations / IMW 2019

Conference call for investors, analysts and the media
CEO Jakob Lindberg will review of the results presented at IMW, on Monday September 16, 2019 at 08:30 (CET).
The conference call will also be streamed via a link on the company website: www.oncopeptides.com.

Phone numbers for participants from:
Sweden: +46 8 505 583 68
Europe: +44 3333 009 271
USA: +1 833 823 05 87

The information in the press release is information that Oncopeptides is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person above, on September 15, 2019 at 14.30 (CET).

About the OP-106 HORIZON study
Patient recruitment in the HORIZON study is ongoing. The interim data presented at IMW 2019 is based on a data cut-off dated July 30, 2019, with 136 patients treated. The goal is to include 150 patients in the study. The patients in the study are refractory to pomalidomide and/or daratumumab after failing on immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs).

Oncopeptides has initiated preparations for submitting a New Drug Application (NDA) for accelerated approval of melflufen in the US based on the available HORIZON data. The detailed plan for the filing process is still under development, but Oncopeptides currently targets to submit the application to FDA during the first quarter of 2020. This could then lead to the first melflufen market approval in the US in 2020.

More information can be found at: View Source;rank=2

About Melflufen
Melflufen is a lipophilic peptide-conjugated alkylator that rapidly delivers a highly cytotoxic payload into myeloma cells through peptidase activity. It belongs to the novel class Peptidase Enhanced Cytotoxics (PEnC), which is a family of lipophilic peptides that exhibit increased activity via peptidase cleavage and have the potential to treat many cancers. Peptidases play a key role in protein homeostasis and feature in cellular processes such as cell-cycle progression and programmed cell death. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and immediately cleaved by peptidases to deliver an entrapped hydrophilic alkylator payload. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the peptidase cleavage, and induces irreversible DNA damage and apoptosis. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies.

On September 14, 2019 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported that our two poster presentations have been made public at the 17th International Myeloma Workshop (IMW) meeting in Boston, Massachusetts, USA (Press release, Oncopeptides, SEP 14, 2019, View Source [SID1234539499]).

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The posters presented at IMW
The first poster presentation was held during Poster Session I, Multiple Myeloma Genomics – under the title: Aminopeptidase gene expression in myeloma.

The second poster presentation was held during Poster Session II, Treatment of Previously Treated Myeloma –under the title: Quality of life treatment for relapsed/refractory multiple myeloma, a systematic review.

The posters are available on the company webpage under:
www.oncopeptides.com / Investors&Media / Presentations / IMW 2019

For further information, please contact:
Jakob Lindberg, CEO of Oncopeptides
E-mail: [email protected]
Telephone: +46 8 615 20 40

Rein Piir, Head of Investor Relations at Oncopeptides
E-mail: [email protected]
Cell phone: +46 70 853 72 92

This information was submitted for publication at 13.00 CET September 14, 2019.

On September 13, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the phase III FeDeriCa study met its primary endpoint (Press release, Hoffmann-La Roche, SEP 13, 2019, View Source [SID1234539487]). The study showed a new investigational fixed-dose combination (FDC) of Perjeta (pertuzumab) and Herceptin (trastuzumab), administered by subcutaneous (SC) injection in combination with intravenous (IV) chemotherapy, demonstrated non-inferior levels of Perjeta in the blood (pharmacokinetics) compared to standard IV infusion of Perjeta plus Herceptin and chemotherapy in people with HER2-positive early breast cancer (eBC). The safety profile of the FDC of Perjeta and Herceptin was consistent with that of Perjeta and Herceptin administered intravenously.1,2

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"With this single injection under the skin, people with HER2-positive breast cancer receiving Perjeta and Herceptin can have a faster treatment option," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Our medicines have helped millions of people living with HER2-positive breast cancer and this latest development is particularly exciting as, for the first time, we have combined two therapeutic antibodies as a single subcutaneous formulation."

SC administration of the FDC takes approximately 8 minutes for the initial loading dose, and approximately 5 minutes for each subsequent maintenance dose. This is compared to approximately 150 minutes for infusion of a loading dose of Perjeta and Herceptin using the standard IV formulations, and between 60-150 minutes for subsequent maintenance infusions for the combination.1,2,3

Full data from the FeDeriCa study will be submitted for presentation at an upcoming medical meeting and to health authorities around the world.

About the FeDeriCa study
FeDeriCa is an international, multi-centre, two-arm, randomised, open-label, phase III study evaluating the pharmacokinetics, efficacy and safety of SC injection of the FDC of Perjeta and Herceptin in combination with chemotherapy, compared with standard IV infusions of Perjeta and Herceptin in combination with chemotherapy in people with HER2-positive eBC who are being treated in the neoadjuvant (before surgery) and adjuvant (after surgery) settings.4 The primary endpoint of the study is minimum levels of Perjeta in the blood during a given dosing interval (Ctrough). Secondary endpoints include safety; minimum levels of Herceptin in the blood during a given dosing interval (Ctrough); and total pCR, meaning there is no tumour tissue detectable at the time of surgery.4

About the FDC of Perjeta and Herceptin
The FDC of Perjeta and Herceptin is a new SC formulation that combines Perjeta and Herceptin with Halozyme Therapeutics’ Enhanze drug delivery technology.

Trastuzumab in the FDC is the same monoclonal antibody as in IV Herceptin and pertuzumab is the same monoclonal antibody as in IV Perjeta. The mechanisms of action of Perjeta and Herceptin are believed to complement each other as both bind to the HER2 receptor, but to different places.5 The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of the HER signaling pathways.5

The standard IV formulation of Perjeta in combination with IV Herceptin and chemotherapy (the Perjeta-based regimen) is approved in over 100 countries for the treatment of both early and metastatic HER2-positive breast cancer. In the neoadjuvant eBC setting, the Perjeta-based regimen has been shown to almost double the rate of pCR compared to Herceptin and chemotherapy.6 Additionally, the combination has been shown to significantly reduce the risk of recurrence of invasive disease or death in the adjuvant eBC setting.7 In the metastatic setting, the combination has shown an unprecedented survival benefit in previously untreated (first-line) patients with HER2-positive metastatic breast cancer.8

Halozyme’s Enhanze drug delivery technology may enable and optimise SC drug delivery for appropriate co-administered therapeutics. The technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that temporarily degrades hyaluronan – a glycosaminoglycan or chain of natural sugars in the body, to aid in the dispersion and absorption of other injected therapeutic drugs.9

About Roche’s medicines for HER2-positive breast cancer
Roche has been leading research into the HER2 pathway for over 30 years and is committed to improving the health, quality of life and survival of people with both early and metastatic HER2-positive disease. HER2-positive breast cancer is a particularly aggressive form of the disease that affects approximately 15-20% of patients.10 Roche has developed three innovative medicines that have helped transform the treatment of HER2-positive breast cancer: Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla (trastuzumab emtansine). Eligibility for treatment with Roche’s HER2-targeted medicines is determined via a diagnostic test which identifies people who will likely benefit from these medicines at the onset of their disease.

On September 13, 2019 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported that the global phase III FeDeriCa study conducted by Genentech, a member of the Roche Group, met its primary endpoint (Press release, Halozyme, SEP 13, 2019, View Source [SID1234539472]). The FeDeriCa study investigated a fixed-dose combination of pertuzumab (Perjeta) and trastuzumab (Herceptin) for subcutaneous administration using Halozyme’s ENHANZE drug delivery technology in combination with intravenous chemotherapy. The study results demonstrated non-inferior levels of Perjeta in the blood (pharmacokinetics) compared to standard intravenous (IV) infusion of Perjeta plus Herceptin and chemotherapy in patients with HER2-positive early breast cancer.

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"The results of the phase III FeDeriCa study represent an important development for our ENHANZE drug delivery technology," said Dr. Helen Torley, President and CEO. "This is the first study to combine two therapeutic antibodies as a single fixed-dose subcutaneous formulation utilizing our ENHANZE technology, thereby providing patients with HER2-positive breast cancer the possibility of a faster treatment option."

Subcutaneous administration of the fixed-dose combination of Perjeta and Herceptin is approximately 8 minutes for the initial loading dose and approximately 5 minutes for each subsequent maintenance dose. Intravenous administration is approximately 150 minutes for the loading dose of Perjeta and Herceptin using standard IV formulations and between 60-150 minutes for subsequent maintenance infusions for the combination.

The study also demonstrated that the safety profile of the fixed dose subcutaneous combination of Perjeta and Herceptin was consistent with the safety profile of Perjeta and Herceptin administered intravenously.

Full data from the FeDeriCa study will be submitted for presentation at an upcoming medical meeting and to health authorities worldwide, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).1 2

About ENHANZE Technology
Halozyme’s proprietary ENHANZE drug-delivery technology is based on its patented recombinant human hyaluronidase enzyme (rHuPH20). rHuPH20 has been shown to remove traditional limitations on the volume of biologics that can be delivered subcutaneously (just under the skin). By using rHuPH20, some biologics and compounds that are administered intravenously may instead be delivered subcutaneously. ENHANZE may also benefit subcutaneous biologics by reducing the need for multiple injections. This delivery has been shown in studies to reduce health care practitioner time required for administration and shorten time for drug administration.

On September 13, 2019 Genmab A/S (Nasdaq: GMAB) reported topline results from the Phase III CANDOR study, sponsored by Amgen, of daratumumab in combination with carfilzomib and dexamethasone (Kd) versus Kd alone in patients with multiple myeloma who have relapsed after one to three prior therapies (Press release, Genmab, SEP 13, 2019, View Source [SID1234539492]). The study met the primary endpoint of improving progression free survival (PFS). The regimen resulted in a 37% reduction in the risk of progression or death in patients with relapsed or refractory multiple myeloma treated with daratumumab in combination with Kd (HR=0.630; 95% CI: 0.464, 0.854; p=0.0014). The median PFS for patients treated with daratumumab in combination with Kd had not been reached by the cut-off date compared to a median PFS of 15.8 months for patients who received Kd alone.

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There was a higher frequency of adverse events reported with daratumumab plus Kd, a three-agent regimen, than with Kd, a two-agent regimen. The types of observed adverse events were consistent with the known safety profiles of the individual agents. The most frequently reported treatment-emergent adverse events (greater than or equal to 20%) in the daratumumab plus Kd arm were thrombocytopenia, anemia, diarrhea, hypertension, upper respiratory tract infection, fatigue and dyspnea.

The CANDOR data will be submitted to a future medical meeting and Amgen will discuss the data with health authorities in preparation for regulatory submissions.

"We are very pleased that daratumumab has shown efficacy in yet another combination regimen – in this case with carfilzomib, a newer member of the proteasome inhibitor class. We look forward to the potential for this combination to provide an additional regimen for patients diagnosed with relapsed multiple myeloma," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

About the CANDOR study
The Phase III trial (NCT03158688) is a randomized, open-label study that includes approximately 460 patients with multiple myeloma who have relapsed after 1 to 3 prior therapies. Patients were randomized to receive either daratumumab in combination with carfilzomib (a proteasome inhibitor) and dexamethasone (a corticosteroid) or carfilzomib and dexamethasone alone. In the daratumumab treatment arm, patients received 8 milligrams per kilogram (mg/kg) on days 1 and 2 of cycle 1, then 16 mg/kg once weekly for the remaining doses of the first 2 cycles, then every 2 weeks for 4 cycles (cycles 3 to 6), and then every 4 weeks for the remaining cycles or until disease progression. In both treatment arms carfilzomib was dosed twice weekly (20 mg/m2 on cycle 1 days 1 and 2 and 56 mg/m2 beginning on cycle 1 day 8 and thereafter) and dexamethasone was given weekly (40 mg orally or via IV infusion). The primary endpoint of the study is 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 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 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.5

About DARZALEX(daratumumab)
DARZALEX (daratumumab) intravenous infusion is indicated for the treatment of adult patients in the United States: 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.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe 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 therapy. 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 is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma and 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).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.