On January 29, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that the European Commission (EC) has granted marketing authorisation for the expanded use of Erleada▼ (apalutamide) to include the treatment of adult men with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT) (Press release, Janssen Pharmaceuticals, JAN 29, 2020, View Source [SID1234553661]).

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"Prostate cancer is the most prevalent form of cancer in men throughout Europe, and the expanded approval of apalutamide marks a significant advancement for those living with mHSPC," said Prof. Dr. med. Axel S. Merseburger, Chairman of the Department of Urology, Campus Lübeck, University Hospital Schleswig-Holstein, Kiel, Germany. "In prostate cancer treatment, our primary goal is always to delay progression of disease and prolong survival, to ensure the best possible outcomes for patients. Today’s news is therefore an encouraging development for patients within Europe, for whom the importance of an additional treatment option that can both delay progression and extend survival cannot be underestimated."

The EC approval is based on data from the Phase 3 TITAN study, which assessed the addition of apalutamide to ADT in a broad range of patients with mHSPC, regardless of disease volume, prior treatment with docetaxel or staging at initial diagnosis. The dual primary endpoints of the study were overall survival (OS) and radiographic progression-free survival (rPFS).2 Apalutamide plus ADT significantly improved OS compared to placebo plus ADT with a 33 percent reduction in the risk of death (HR=0.67; 95% CI, 0.51-0.89; p=0.0053).2 In both study arms, median OS was not reached.2 Apalutamide plus ADT also significantly improved rPFS compared to placebo plus ADT with a 52 percent reduction in risk of radiographic progression or death compared to placebo plus ADT (HR=0.48; 95% CI, 0.39-0.60; p<0.0001).2 The median rPFS was 22.1 months for placebo plus ADT and not reached for apalutamide plus ADT.2 The two-year OS rates, after a median follow up of 22.7 months, were 82 percent for apalutamide plus ADT compared to 74 percent for placebo plus ADT.2 These results were published in The New England Journal of Medicine.2,3

The safety profile observed in the TITAN study for apalutamide plus ADT was consistent with that described in previous studies. In the study, 42 percent of patients on apalutamide plus ADT experienced Grade 3/4 adverse events (AEs), compared to 41 percent of patients on placebo plus ADT.2 The most common Grade ≥3 AEs for apalutamide plus ADT versus placebo plus ADT were hypertension (8.4 percent vs. 9.1 percent) and skin rash (6.3 percent vs. 0.6 percent). Treatment discontinuation due to AEs was 8 percent in the apalutamide arm compared to 5 percent in the placebo arm.2

"We are delighted with the EC’s approval of the extended use of apalutamide, which makes an important treatment option potentially available to over 100,000 patients living with mHSPC across Europe," said Joaquín Casariego, M.D., Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen-Cilag S.A. "It is vital to fight cancer at this stage of the disease with an efficacious new line of treatment, to delay progression to the late and fatal mCRPC stage and, crucially, prolong survival. Janssen remains committed to transforming treatment outcomes for patients and improving lives throughout the prostate cancer journey."

"We continue to be encouraged by the clinical trial data for apalutamide, which demonstrates that the addition of apalutamide to ADT improves outcomes for a broad range of patients with mHSPC, compared to ADT alone," said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology at Janssen Research & Development, LLC. "This approval is welcome news for patients with mHSPC and highlights our focus of addressing areas of high unmet need across the prostate cancer disease continuum."

In Europe, apalutamide is also approved for use in adults with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease.4

About the TITAN Study2,3
TITAN is a Phase 3 randomised, placebo-controlled, double-blind study in men with mHSPC regardless of extent of disease or prior docetaxel treatment history. The study included 1,052 patients in intention-to-treat (ITT) population in 23 countries across 260 sites in North America, Latin America, South America, Europe and Asia Pacific. Patients with mHSPC were randomised 1:1 and received either apalutamide (240 mg) plus continuous androgen deprivation therapy (ADT) (n=525), or placebo plus ADT (n=527). The recruitment period for the study spanned from December 2015 to July 2017. The study included a broad population of patients with mHSPC, including patients with both low- and high-volume disease, those who were newly diagnosed, or those who had received prior definitive local therapy or prior treatment with up to six cycles of docetaxel or up to six months of ADT for mHSPC. Participants were treated until disease progression or the occurrence of unacceptable treatment-related toxicity. An independent data-monitoring committee was commissioned by the sponsor to monitor safety and efficacy before unblinding and make study conduct recommendations. Dual primary endpoints of the study were OS and rPFS. Secondary endpoints included time to cytotoxic chemotherapy, time to pain progression, time to chronic opioid use and time to skeletal-related event. Exploratory endpoints included time to PSA progression, time to second progression-free survival and time to symptomatic progression. For additional study information, visit ClinicalTrials.gov.

About apalutamide
Apalutamide is an androgen receptor (AR) inhibitor indicated for use in Europe for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease and metastatic hormone-sensitive prostate cancer (mHSPC).4 In the U.S. apalutamide is indicated for the treatment of nmCRPC and mHSPC.5

About Metastatic Hormone-Sensitive Prostate Cancer
Metastatic hormone-sensitive prostate cancer (mHSPC), also referred to as metastatic castration sensitive prostate cancer (mCSPC), refers to prostate cancer that still responds to androgen deprivation therapy (ADT) and has spread to other parts of the body.6 Patients with mHSPC tend to have a poor prognosis, with a median overall survival (OS) of less than five years, underscoring the need for new treatment options.7,8,9

On January 29, 2020 Starpharma (ASX: SPL, OTCQX: SPHRY) reported its Appendix 4C – Quarterly Cashflow Report for the period ended 31 December 2019 (Press release, Starpharma, JAN 29, 2020, View Source [SID1234553660]).

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Starpharma’s cash balance as at 31 December 2019 was $35.9 million, with net operating cash outflows for the quarter of $0.5 million, compared to $4.6 million last quarter. Receipts for the quarter included the $4.9 million R&D tax incentive refund received in December 2019. Product supply and royalty receipts for VivaGel BV totalled $0.9 million for the quarter.

The cash balance does not include the anticipated US$3 million milestone payment from AstraZeneca which is expected to be received during the March quarter.

Cash outflows for the quarter include the manufacture of VivaGel BV product to support the roll-out in multiple regions, including the UK, Eastern Europe and Asia. Cash outflows also included expenditure on Starpharma’s three DEP clinical programs, including several new sites across the DEP studies. Outflows also included expenditure on the dual strategy to achieve FDA approval through the formal review process, as well as preparation, including start-up activities, for a possible VivaGel BV treatment clinical trial.

Key recent events:

AstraZeneca commenced the phase 1 clinical trial of its first DEP product, AZD0466. The successful dosing of the first patient in this trial triggered a US$3 million milestone payment, which is expected to be received in the coming weeks.
DEP cabazitaxel trial progressed from phase 1 to phase 2 on positive results. The trial met its objective of evaluating safety, tolerability and preliminary efficacy data, and identifying a recommended phase 2 dose. The trial transitioned seamlessly into phase 2, with two new sites initiated and recruitment underway.
Patients continue to be recruited into the phase 2 trial for DEP docetaxel, with efficacy signals observed in a variety of tumour types including non-small cell lung cancer, prostate cancer, and several hard to treat tumours. Six sites in the UK are currently recruiting patients, including two new sites – the Christie and the Beatson (Glasgow).
Patients continue to be recruited into the dose escalation phase of the phase 1/2 trial for DEP The three leading cancer sites actively recruiting for this trial are the Christie, the Royal Marsden and Newcastle Freeman Hospital.
VivaGel BV was launched in the UK under the brand Betafem BV Gel.
Starpharma supplied product to Mundipharma to support the roll-out of VivaGel BV in Europe, including countries in Central and Eastern Europe, where launches are expected in the coming months.
Further regulatory approvals were granted in Asia. Advanced marketing activities are underway, and product has been delivered by Starpharma in preparation for launch.
Aspen continued to advance their marketing and promotional activities for Fleurstat BVgel in Australia, and preparations have progressed for the New Zealand launch, including product supply by Starpharma and training of sales representatives.
Starpharma progressed its dual strategy regarding FDA approval of VivaGel BV with ongoing support from a team of expert FDA consultants (regulatory, statistical, clinical, legal; several ex-FDA). This includes seeking formal review of some of the FDA’s initial conclusions, as well as preparation for a possible BV treatment trial.
VivaGel condom was granted marketing approval in Europe. LifeStyles has commenced marketing preparations ahead of the launch of the VivaGel condom under the brand name Absolute DUAL PROTECTION.
New DEP candidate, DEP gemcitabine, was advanced for development upon demonstrating significantly enhanced anti-tumour activity compared with Gemzar (gemcitabine), both alone and in combination with Nab‑paclitaxel (Abraxane), in a human pancreatic cancer model.
Several new DEP patents were filed covering DEP in combination with marketed anticancer agents and novel DEP
Dr Jackie Fairley, Starpharma CEO, commented: "It was a key milestone for Starpharma to see AstraZeneca treat its first patient with our partnered DEP product, AZD0466. AstraZeneca describes AZD0466 as having the potential to be a ‘best-in-class’ agent in this field due to its ability to target both Bcl2 and Bcl/xL. We will follow the progress of the AZD0466 trial, which is currently being conducted in multiple sites in the US, with interest. In our internal portfolio, we progressed DEP cabazitaxel into phase 2 on positive phase 1 results and we delivered excellent data on our new candidate, DEP gemcitabine. With four DEP products now in the clinic, and a pipeline of high-potential candidates, the DEP platform is generating a deep portfolio of valuable products".

"We also achieved key milestones for VivaGel BV, with the launch into the UK market. We continue to work closely with our partners to support the roll-out in Europe and Asia, as well as the New Zealand launch. In the last few months, several submissions have also been prepared and submitted for countries in other regions. During the next quarter we are focussed on accelerating our clinical trials, wherever possible, and working towards further regulatory approvals and launches for VivaGel BV," concluded Dr Fairley.

On January 29, 2020 PharmaMar (MSE:PHM) reported that it has received the upfront payment of $200 million from the agreement signed with Jazz Pharmaceuticals on 19 December 2019 (Press release, PharmaMar, JAN 29, 2020, View Source [SID1234553659]).

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This license agreement for the commercialization of lurbinectedin in the United State became effective with the expiration of the Hart-Scott-Rodino waiting period.

Under the terms of the agreement, PharmaMar is also eligible to receive, in the following months, potential regulatory milestone payments of up to $250 million upon the achievement of accelerated and/or full regulatory approval of lurbinectedin by FDA within certain timelines.

PharmaMar is also eligible to receive up to $550 million in potential commercial milestone payments, as well as incremental tiered royalties on future net sales of lurbinectedin ranging from the high teens up to 30%.

There is the potential for other regulatory milestones on FDA approval of other indications beyond relapsed small cell lung cancer.

About Lurbinectedin
Lurbinectedin (PM1183) is a synthetic compound currently under clinical investigation. It is a selective inhibitor of the oncogenic transcription programs on which many tumors are particularly dependent. Together with its effect on cancer cells, lurbinectedin inhibits oncogenic transcription in tumor-associated macrophages, downregulating the production of cytokines that are essential for the growth of the tumor. Transcriptional addiction is an acknowledged target in those diseases, many of them lacking other actionable targets.

On January 29, 2020 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, Precision Cancer Medicine oncology therapeutics company developing drugs that target cell division (mitosis) for the treatment of various cancers including prostate, colorectal and leukemia, reported that it has received approximately $1.45 million in proceeds from holders exercising common stock purchase warrants at an exercise price of $1.56 per share (Press release, Trovagene, JAN 29, 2020, View Source [SID1234553658]). The warrants were issued as part of the units sold to certain institutional investors in October, 2019.

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Trovagene intends to use the proceeds to continue funding its clinical development activities and for working capital and general corporate purposes.

"We continue to see clinical benefit in patients receiving onvansertib as part of combination therapy in all three of our clinical development programs," said Dr. Thomas Adams, CEO and Chairman of Trovagene. "Earlier this week, we presented positive data from our Phase 1b/2 study in patients with difficult-to-treat KRAS-mutated metastatic colorectal cancer (mCRC); all of whom are achieving a meaningful clinical response which has been confirmed by shrinking of tumors seen on radiographic scans. Additionally, on February 13th, we will be presenting data from our ongoing Phase 2 trial in patients with metastatic castrate-resistant prostate cancer (mCRPC) at the ASCO (Free ASCO Whitepaper)-GU conference."

On January 29, 2020 Verastem, Inc. (Nasdaq: VSTM), (Verastem Oncology or the Company), a biopharmaceutical company focused on developing and commercializing medicines seeking to improve the survival and quality of life of cancer patients, reported that its partner CSPC Pharmaceutical Group Limited (HKEx: 1093) (CSPC), a leading pharmaceutical company in China, has dosed the first patient in a pivotal Chinese bridging study evaluating COPIKTRA (duvelisib) in patients with relapsed or refractory follicular lymphoma (FL) (Press release, Verastem, JAN 29, 2020, View Source [SID1234553657]). COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma in the United States.

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"Building on CSPC’s strong track record of successfully developing and commercializing oncology products in China, we are pleased that this CSPC trial is now underway as they work to provide a new option for patients with follicular lymphoma in China, where there are limited options for this difficult to treat disease," said Brian Stuglik, Chief Executive Officer of Verastem Oncology. "The first patient dosed in this trial is a critical step in our mission to bring COPIKTRA to patients around the world."

In September of 2018, Verastem Oncology and CSPC entered into an exclusive licensing agreement for CSPC to develop and commercialize Verastem Oncology’s COPIKTRA for the treatment of all oncology indications in China. CSPC’s single-arm, open-label, multi-center pivotal study is designed to evaluate the antitumor activity and safety of duvelisib administered to patients diagnosed with relapsed or refractory follicular lymphoma. This study is expected to serve as a bridging study based on the efficacy and safety observed in Verastem Oncology’s Phase 2 DYNAMO study. The results of this study will form the basis of a regulatory submission for COPIKTRA for the treatment of relapsed or refractory FL in China.

COPIKTRA was approved in September 2018 by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies. COPIKTRA also received accelerated approval for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. Continued approval in FL may be contingent upon verification and description of clinical benefit in confirmatory trials.

About COPIKTRA (duvelisib)

COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells, in the United States. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 COPIKTRA is indicated in the United States for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies and relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. COPIKTRA is also being developed by Verastem Oncology for the treatment of peripheral T-cell lymphoma (PTCL), for which it has received Fast Track status in the United States, and is being investigated in combination with other agents through investigator-sponsored studies.4 For more information on COPIKTRA, please visit www.COPIKTRA.com. Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

SELECT IMPORTANT SAFETY INFORMATION

This does not include all information needed to use COPIKTRA (duvelisib) safety and effectively. See full Prescribing Information.

WARNING: FATAL AND SERIOUS TOXICITIES: INFECTIONS, DIARRHEA OR COLITIS, CUTANEOUS REACTIONS, and PNEUMONITIS

See full Prescribing Information for complete boxed warning

Fatal and/or serious infections occurred in 31% (4% fatal) of COPIKTRA-treated patients. Monitor for signs and symptoms of infection. Withhold COPIKTRA if infection is suspected.
Fatal and/or serious diarrhea or colitis occurred in 18% (<1% fatal) of COPIKTRA-treated patients. Monitor for the development of severe diarrhea or colitis. Withhold COPIKTRA.
Fatal and/or serious cutaneous reactions occurred in 5% (<1% fatal) of COPIKTRA-treated patients. Withhold COPIKTRA.
Fatal and/or serious pneumonitis occurred in 5% (<1% fatal) of COPIKTRA-treated patients. Monitor for pulmonary symptoms and interstitial infiltrates. Withhold COPIKTRA.
INDICATIONS AND USAGE

COPIKTRA is a kinase inhibitor indicated for the treatment of adult patients with:

Relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies.
Relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. Accelerated approval based on overall response rate and continued approval may be contingent upon confirmatory trials.
WARNINGS AND PRECAUTIONS

Hepatotoxicity: Monitor hepatic function.
Neutropenia: Monitor blood counts.
Embryo-Fetal toxicity: COPIKTRA can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
ADVERSE REACTIONS

The most common adverse reactions (≥20%) are diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.

To report Adverse Reactions, contact FDA at 1-800-FDA-1088 (1-800-332-1088) or www.fda.gov/medwatch and Verastem Oncology at 1-877-7RXVSTM (1-877-779-8786).

DRUG INTERACTIONS

CYP3A inducers: Avoid co-administration with strong CYP3A inducers.
CYP3A inhibitors: Monitor for COPIKTRA toxicities when co-administered with strong or moderate CYP3A inhibitors. Reduce COPIKTRA dose to 15 mg twice daily when co-administered with strong CYP3A4 inhibitors.
CYP3A substrates: Monitor for signs of toxicities when co-administering COPIKTRA with sensitive CYP3A substrates.