AwesomeCapital

Saturday, June 1, 2019

J&J unveils early-stage prostate cancer data from Erleada at ASCO

Johnson & Johnson is hoping to expand the use of its prostate cancer drug Erleada (apalutamide) in patients with metastatic castration-sensitive prostate cancer (mCSPC) – and new data presented at ASCO sheds light on the dossier under review at the FDA for this early stage disease.

Developed by J&J’s pharma unit Janssen, Erleada is already approved in the big battle ground in prostate cancer – castration resistant metastatic disease – where its big rival is Pfizer/Astellas’ Xtandi (enzalutamide) and generics of its older drug Zytiga (abiraterone).

Data published at ASCO, and simultaneously in the New England Journal of Medicine (NEJM) showed adding Erleada to androgen deprivation therapy (ADT), compared with placebo plus ADT, significantly improved the dual primary endpoints of overall survival (OS) and radiographic progression-free survival (rPFS) in mCSPC.

The study included patients with mCSPC regardless of extent of disease or prior docetaxel treatment history.

Data show Erleada plus ADT significantly extended OS compared with placebo plus ADT, with a 33% reduction in risk of death.

It also significantly improved rPFS compared to placebo plus ADT with a 52% reduction in risk of radiographic progression or death compared to placebo plus ADT.

The two-year OS rates, after a median follow-up of 22.7 months, were 82% for Erleada plus ADT compared to 74% for placebo plus ADT.

A secondary endpoint of prolonged time to cytotoxic chemotherapy in patients treated with Erleada plus ADT was also met, with a 61% risk reduction compared with placebo.

In exploratory endpoints, median time to PSA progression was more favourable following Erleada plus ADT, compared with placebo plus ADT, and prostate-specific antigen (PSA) reached undetectable levels in 68% of patients in the Erleada plus ADT arm and 29% of patients in the placebo plus ADT arm.

Erleada plus ADT, compared with placebo plus ADT, achieved a 34% risk reduction in median time to second progression-free survival (PFS2), defined as time from randomisation to either disease progression on first subsequent anticancer therapy or death, whichever occurred first.

The biggest issue safety-wise was a rash, seen in 27% of patients although investigator Dr Kim Chi said most cases were Grade 1 or 2. Overall the safety profile was consistent with previous experience of the drug, he noted.

It’s bad form to pre-judge whether the FDA will approve or not, but the response from oncologists gathered at ASCO seemed to be favourable.

And while the data has gone down well in Chicago, there are also several other phase 3 studies involving rival therapies such as Bayer’s darolutamide, Pfizer/Astellas’ Xtandi, and Takeda’s orteronel – which could provide competition even if the FDA does grant a new indication.

J&J unveils early-stage prostate cancer data from Erleada at ASCO

AstraZeneca, Merck data support PARP drug in prostate cancer

PARP, or poly (ADP-ribose) polymerase, inhibitors may have an amusing-sounding name but an increasing body of evidence suggest they could be used in a wide range of cancers as long as certain mutations are present.

PARP drugs work by interfering with cancer cells’ DNA repair system, eventually causing them to self-destruct – and AstraZeneca and Merck & Co’s Lynparza (olaparib) was the trailblazer in this drug class after first approval in ovarian cancer in 2014.

But since then the drug has gone on to be approved in breast cancer, and it looks possible that prostate cancer could be another use.

Clovis Oncology already unveiled data from the TRITON2 study at the European Society for Medical Oncology (ESMO) conference in the autumn that suggest its drug Rubraca (rucaparib) could be an option in this disease.

And the latest data from AZ and Merck & Co suggest olaparib could be a potential competitor in metastatic castration resistant prostate cancer (MCRPC) with DNA damage repair mutations.

This was a mid-stage trial that was expanded from an initial phase 1 trial to determine dose – and the study’s designers opted to include a patient arm treated with a lower 300ml dose of the drug, as well as the 400ml dose.

This was because of a regulatory update as olaparib was approved at the lower dose in ovarian cancer after it was first launched.

The strongest response rate from olaparib in TOPARP-B (54%) was seen in patients treated with a higher dose (400ml twice daily), although those on the more recently approved 300ml regime also benefited with a response rate of 39%.

But the results also suggested that response changed according to sub-groups of patients with different DNA damage repair mutations.

Expert Mary-Ellen Taplin, of the Dana Farber Cancer Institute, praised the design of the study in an analysis and was supportive of olaparib’s potential in this new indication.

But she did raise an issue about how this drug could be used in a real-life setting: selecting patients with the mutations that are most likely to respond could be tricky.

“The experience provided warns that identifying appropriate patients within routine clinical practice will be challenging and will require repeated testing,” she said.

This could prove a difficult technical challenge – but the data were well received by clinicians gathered at the conference in Chicago.

American Society of Clinical Oncology’s annual meeting in Chicago, Day 2

Just spoke with Anders Bjartell, Professor of Urological Cancer, Lund University, Sweden about the data from the TITAN trial yesterday.

As a trial investigator he’s naturally really excited about the data, and he also raised some interesting points about the future of prostate cancer research. He agreed with the comments made in the oral presentation session yesterday about the need for more accurate testing to identify which mutations are present, as this has a big impact on prognosis.

Then I had a chat with Scott Koenig, CEO of Macrogenics about the company’s new breast cancer drug margetuximab. The biotech made waves ahead of the conference with data showing a survival benefit in patients previously treated with existing cancer drugs like Herceptin.

The company aims to file with the FDA based on the progression-free survival data, and will look to confirm this with further data next year about overall survival.

Right now that data is not ready but it will be interesting to see if the PFS benefit seen in the early data from the phase 3 SOPHIA trial translates into an overall survival benefit, and what the magnitude of that benefit will be.

I will be doing more in-depth coverage of these interviews on pharmaphorum later.

2 hours ago

ASCO launches mCODE to improve e-health record compatibility

ASCO has identified a huge issue that is holding back progress in cancer care – and it’s quite a basic problem.

Getting the disparate computer systems across the U.S. and the rest of the world to share electronic health record data effectively is a major problem, said ASCO president Monica Bertagnolli.

There are 15 million people with cancer in the U.S. but many electronic health record systems use different terms to describe the same type of data, or collect data in different formats, making them incompatible.

According to ASCO this dramatically limits the ability of cancer researchers and doctors to learn from patient records, hinders care coordination, and adds to admin costs for all uses, but especially practices and patients.

Most patients assume that in these modern times it should be easy for doctors to communicate details about their disease and treatment.

But not so, according to Bertagnolli, as getting different systems to interact and read patients’ electronic records is proving to be a real challenge.

ASCO is trying to solve this problem with mCODE (Minimal Common Oncology Data Elements), a core set of data elements and recommended technical specs that it considers essential for capturing and reporting patient data, and should be captured in each patient’s electronic health record.

mCODE is a collaboration between ASCO, its wholly owned non-profit subsidiary CancerLinQ, and the Alliance for Clinical Trials in Oncology Foundation..

The standards and specs have been published online at mCODEinitiative.org.

Bertagnolli added in a question and answer session that it was her “dream” to make the system available worldwide to improve communication between oncologists on a global scale.

3 hours ago

ASCO experts noted that this and other data from immunotherapies is changing the way doctors think about patients with lung cancer.

The chances of patients surviving for extended periods of time with the disease have increased considerably.

In the past only a handful of lung cancer patients would survive past five years, but with immunotherapy around a quarter could be expected to live that long.

3 hours ago

New data unveiled at ASCO shows how Merck & Co’s Keytruda (pembrolizumab) and other immunotherapies could change the outlook for seriously ill lung cancer patients.

The latest data came from a phase 1a study, KEYNOTE – 001, which as its name suggests was one of the first cancer immunotherapy trials that began in 2011 in patients with solid tumours.

There were 550 people with advanced non-small cell lung cancer on the trial, including 101 patients who had not previously received any treatment and 449 who had received treatment previously.

After a median follow-up of 60.6 months – around five years – and at that point 18% of enrolees (100 people) were still alive.

Of those who had not received prior treatment, 23% were still alive after five years compared with 15.5% of those previously treated.

Higher levels of the biomarker PD-L1 predicted longest survival – in previously untreated people 29.6% with PD-L1 expression of 50% or more were alive after five years, compared with 12.6% with expression levels between one to 49%. Only 3.5% of people with expression levels below 1% were alive after five years.

Among previously treated patients, 42% had responses that lasted for a median of 16.8 months, while for those who were treatment naïve, 23% had responses that lasted for a median of 38.9 months.

3 hours ago

Another interesting point from that briefing on MONALEESA-7 – the survival data could also be important in countries carrying out health technology assessment to decide whether drugs should be available in national health systems.

ASCO expert Harold Burstein said: “Demonstration of robust survival adds to a value proposition for ribociclib and this could be helpful for health systems that measure value to decide on national access to drugs.”

Novartis looks to have gained an advantage in its battle with Pfizer and Eli Lilly in the CDK4/6 class of breast cancer drugs after its Kisqali became the first to show an overall survival benefit in a subgroup of younger patients.

Results of the phase 3 MONALEESA-7 trial found that adding Kisqali (ribociclib) to standard-of-care endocrine therapy significantly improved overall survival for premenopausal women with advanced HR-positive/HER2-negative breast cancer patients compared with endocrine therapy alone.

Data unveiled today at ASCO show the survival rate was 70% for women who took the combination therapy compared with 46% for women who received endocrine therapy only.

Women who received Kisqali lived a median 23.8 months without the disease progressing compared with 13 months for women who received placebo.

The trial was the first to focus exclusively on women under age 59 who were premenopausal and had advanced breast cancer for which they had not received prior endocrine therapy.

Investigators randomly assigned women to Kisqali or placebo and all received goserelin to suppress the oestrogen that drives the disease, and one of three other established therapies – letrozole, anastrozole, or tamoxifen.

In all, 672 women enrolled on the study and after a median follow-up of 34.6 months, 173 (26%) were still receiving the therapies, with 116 women still receiving Kisqali and 57 still receiving placebo.

Speaking at a press briefing to unveil the results, Sara Hurvitz, director of the Breast Cancer Clinical Research Program at UCLA, said that until now doctors were likely to use Kisqali, or Pfizer’s rival Ibrance (palbociclib) or Lilly’s Verzenio (abemaciclib) interchangeably.

But this could change with the survival data announced today – at least until Novartis’ rivals produce similar data, said Hurvitz.

Novartis’ data “could change the way physicians practice,” said Hurvitz at the press briefing in a question and answer session.

4 hours ago

Just came out of the morning press conference – I will have updates on new data from Novartis’ breast cancer drug Kisqali, and Merck & Co’s immunotherapy Keytruda shortly.

7 hours ago

AZ/Merck & Co reveal olaparib data in prostate cancer

Data presented yesterday at ASCO 2019 from AZ and Merck & Co suggest their PARP inhibitor olaparib could be a potential competitor in metastatic castration resistant prostate cancer (MCRPC) with DNA damage repair mutations.

8 hours ago

ASCO 2019 – Kantar takes a first look at interim TITAN data

Will Erleada take the lead in metastatic CSPC? New interim data at ASCO 2019 from the phase 3 TITAN trial supports addition of Erleada to ADT for a broad range of patients in this setting.

8 hours ago

J&J’s early-stage prostate cancer data from Erleada

Johnson & Johnson is hoping to expand the use of its prostate cancer drug Erleada (apalutamide) in patients with metastatic castration-sensitive prostate cancer (mCSPC) – and new data presented yesterday at ASCO 2019 sheds light on the dossier under review at the FDA for this early stage disease.

https://pharmaphorum.com/asco-chicago-2019

NRG oncology trial of metformin for non-small cell lung cancer

Initial results of NRG-LU001 indicate that, although the diabetes agent metformin was well-tolerated by patients, the agent has not clearly improved progression-free survival (PFS) or overall survival (OS) for trial participants with locally advanced non-small cell lung cancer (NSCLC). These results are based on local center reported outcomes. Trial participants will continue to be followed for changes in their status. The initial report of these results were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting and the abstract was awarded a “Best of ASCO” designation.

“In previous pre-clinical studies, metformin enhanced the response of human non-small cell lung cancer (NSCLC) models to radiotherapy and chemotherapy,” stated Dr. Theodoros Tsakiridis, MD, PhD, of McMaster University and lead author of the NRG-LU001 abstract. “The pre-clinical data suggested a potential benefit for patients with lung cancer. For that, we pursued the NRG-LU001 trial to examine whether metformin could indeed improve outcomes in patients with stage III NSCLC treated with standard of care chemotherapy and radiotherapy.”

In NRG-LU001 patients were randomly assigned either to the control arm that received standard chemotherapy and radiotherapy alone or to the experimental arm that received chemotherapy, radiotherapy, and 2000mg of metformin per day during those treatments. This study was designed to detect a 15% improvement in 12-month PFS from 50% to 65% or, equivalently, a HR of 0.622. Following treatment, researchers tracked the participating patients for changes in survival outcomes, toxicities or side effects, time to local-regional progression (TTLRP), and time to distant metastasis (TTDM).

NRG-LU001 closed to accrual in December 2016 after completing accrual and randomization of the pre-planned number of 168 patients. There was no statistically significant difference in rates or grade of toxicity between the two arms, indicating that metformin was well-tolerated by patients. At the time of analysis, local centers reported 102 PFS events. The 1- and 2-year PFS rates were 60.4% (95% CI: 48.5, 70.4) and 40.1% (95% CI: 29.0, 51.0) in the control arm, and 51.3% (95% CI: 39.8, 61.7) and 34.5% (95% CI: 24.2, 45.1) in the experimental treatment arm with metformin. OS at 2 years was 65.4% (95% CI: 53.5, 75.0) in the control arm and 64.9% (95% CI:53.1, 74.5) in the experimental arm (HR=1.03 (95% CI: 0.64, 1.68). Deaths were due to lung cancer in 90% of the control arm and 71% of the experimental arm. These initial results of NRG-LU001 yielded no differences between treatment arms for TTLRP and TTDM.

“While finding no difference in the primary endpoint, between treatment arms was disappointing, we are heartened to observe better than expected PFS and OS rates in both arms of this study” said Dr. Heath Skinner, MD, PhD of the UPMC Hillman Cancer Center who was Co-Principal Investigator of the trial, along with Dr. Tsakiridis. “We plan to complete secondary analyses with a central clinical and radiological review of all cases, as well as biomarker studies involving the biospecimens collected during this trial.”

The results of NRG-LU001 demonstrate the value of continued investigation of NSCLC, one of the deadliest cancers worldwide, in multi-institutional settings such as NRG-Oncology.

This project was supported by National Cancer Institute (NCI) grants: U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), UG1CA189867 (NCORP), U24CA180803 (IROC).

###

Citation

Tsakiridis T*, Hu C, Skinner H*, Santana-Davila R, Lu B, Erasmus JJ, Doemer AJ, Videtic GMM, Coster J, Yang AX, Lee RY, Werner-Wasik M, Schaner PE, McCormack SE, Esparaz BT, McGarry RC, Bazan J, Struve T, Bradley JD. Initial reporting of NRG-LU001, randomized phase II trial of concurrent chemoradiotherapy (CRT) +/- metformin HCL in locally advanced Non-Small Cell Lung Cancer (NSCLC). Abstract presented at the annual meeting of the American Society of Clinical Oncology (ASCO). Chicago, IL.

*authors contributed equally to this work.

About NRG Oncology

NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG). The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.

https://www.eurekalert.org/pub_releases/2019-06/no-not053119.php

Biotech Investors: Mark Your Calendar For These June FDA Dates

The FDA approval machinery worked overtime in May, with several new labelings, original approvals and new molecule approvals coming through in the month.

The month saw the approval of two new molecular entities, or NMEs: Novartis AG NVS 0.22%‘s Piqray in combination with fulvestrant to treat postmenopausal women and men, with hormone HR-positive HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer and Pfizer Inc. PFE 0.88%‘s Vyndaqel and Vyndamax capsules for treating heart disease caused by transthyretin-mediated amyloidosis.

Novartis also won approval for Zolgensma, its novel gene therapy for spinal muscular atrophy Type 1.

PDUFA dates are deadlines for the FDA to review new drugs. The FDA is normally given 10 months to review new drugs. If a drug is selected for priority review, the FDA is allotted six months to review the drug. These time frames begin on the date that an NDA is accepted by the FDA as complete.

Here are the key PDUFA dates to watch for June.

Merck Seeks Approval For Expanded Indication For Antibiotic

Company: Merck & Co., Inc. MRK 0.61%
Type of Application: sNDA
Candidate: Zerbaxa (ceftolozone and tazobactam)
Indication: Treating adult patients with ventilated nosocomial (hospital-acquired) pneumonia
Date: June 3

Zerbaxa is indicated for the treatment of adult patients with complicated urinary tract infections, including pyelonephritis, caused by certain susceptible gram-negative microorganisms, and also for the treatment of adult patients with complicated intra-abdominal infections in combination with metronidazole.

In April, Merck released the results of a Phase 3 trial, showing non-inferiority of Zarbaxa to meropenem, the active comparator, in the primary and key secondary endpoints.

Xeris’ Glucagon Autoinjector For Low Blood Sugar

Company: Xeris Pharmaceuticals Inc XERS 4.44%
Type of Application: NDA
Candidate: Gvoke HypoPen
Indication: Treating severe hypoglycemia in people with diabetes
Date: June 10

Gvoke HypoPen is Xeris’ lead product candidate – a ready-to-use, room-temperature stable liquid glucagon rescue pen auto injector. Glucagon is the standard-of-care for treating severe hypoglycemia.

“Compared to the current glucagon rescue option for people with diabetes who are at risk for severe hypoglycemia, the Xeris glucagon rescue pen would eliminate the need for reconstitution and dramatically simplify the preparation and administration process,” according to Xeris.

Can Merck Snatch Another Approval For Keytruda?

Company: Merck
Type of Application: sBLA
Candidate: Keytruda
Indication: First-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma, or HNSCC
Date: June 10

The FDA accorded priority review status for the application, and Keytruda is being evaluated as a monotherapy, or in combination with platinum and 5-fluorouracil chemotherapy. The application is supported by the pivotal Phase 3 KEYNOTE-048 trial, in which Keytruda demonstrated a significant improvement in overall survival compared with the standard-of-care.

Merck’s Keytruda For Lung Cancer

Company: Merck
Type of Application: sBLA
Candidate: Keytruda
Indication: For treating patients with advanced small cell lung cancer, or SCLC, whose disease has progressed after two or more lines of prior therapy
Date: June 17

The regulatory submission was based on data from the SCLC cohorts of the Phase 2 KEYNOTE-158 and Phase 1b KEYNOTE-028 trials.

Palatin’s Drug For Hypoactive Sexual Desire Disorder Awaits

Company: AMAG Pharmaceuticals, Inc. AMAG 1.75% and Palatin Technologies, Inc. PTN 3.85%
Type of Application: NDA
Candidate: Vyleesi (bremelanotide)
Indication: Treating premenopasal women with hypoactive sexual desire disorder, or HSDD
Date: June 23

Vyleesi is a novel melanocortin 4 receptor agonist under evaluation for restoring a natural sexual desire in premenopausal women with HSDD. It’s administered as a subcutaneous injection under the skin using a single-use autoinjector pen. The drug developed by Palatin is being licensed to Amag.

The original PDUFA date of March 23 was pushed forward by three months to allow the regulatory agency to parse through additional Phase 1 data submitted by the company at FDA’s request.

Acer Seeks Approval For Drug To Treat Rare Genetic Disease of Connective Tissue

Company: Acer Therapeutics Inc ACER 2.69%
Type of Application: NDA
Candidate: Edsivo
Indication: Treatment of vascular Ehlers-Danlos syndrome, or vEDS, in patients with a confirmed type III collagen (COL3A1) mutation
Date: June 25

Ehlers-Danlos Syndrome is a group of hereditary disorders of connective tissues, with vEDS being the most severe subtype, where patients suffer from life-threatening arterial dissections and ruptures, as well as intestinal and uterine ruptures. The drug has received Orphan Drug Designation in 2015 and the NDA has been granted priority review as well.

Can Dupixent Get The Nod For Expanded Indication?

Company: Sanofi SA SNY 1% and Regeneron Pharmaceuticals Inc REGN 2.03%
Type of Application: sBLA
Candidate: Dupixent
Indication: Add-on maintenance treatment for adults with inadequately controlled severe chronic rhinosinusitis with nasal polyps, or CRSwNP
Date: June 26

Dupixent has already been approved for eczema and as a maintenance therapy in combination with other medicines for asthma.

“Currently, there are no FDA-approved biologic medicines to treat CRSwNP, a chronic disease of the upper airway predominantly driven by type 2 inflammation and characterized by polyps that obstruct the sinuses and nasal passages,” the company said.

Can Alexion’s Soliris Pass The Muster For NMOSD?

Company: Alexion Pharmaceuticals, Inc. ALXN 5.65%
Type of Application: sBLA
Candidate: Soliris (eclizumab)
Indication: for treating patients with neuromyelitis optica spectrum disorder, or NMOSD
Date: June 28

The sNDA was supported by comprehensive data from the PREVENT study in patients with anti-AQP4 auto antibody-positive NMOSD, who represent three-quarters of all patients with NMOSD.

NMOSD is a rare, complement-mediated disorder of the central nervous system characterized by relapses. Each relapse results in stepwise accumulation of disability, including blindness and paralysis, and sometimes premature death. There is currently no FDA-approved therapy for the indication.

Retrophin Awaits FDA Nod For New Formulation Of Rare Kidney Disorder Drug

Company: Retrophin Inc RTRX 0.05%
Type of Application: NDA
Candidate: new formulation of Thiola (tiopronin)
Indication: Treatment of cystinuria
Date: June 30

Dova’s Bleeding Disorder Drug On Course For Snagging Another Approval

Company: Dova Pharmaceuticals Inc DOVA 1.56%
Type of Application: sNDA
Candidate: Doptelet (avatrombopag)
Indication: Treatment for patients with chronic immune thrombocytopenia, or ITP, who have had an inadequate response to prior treatment
Date: June 30

Allergan Seeks Label Expansion For Botox

Company: Allergan plc AGN 0.46%
Type of Application: sNDA
Candidate: Botox
Indication: Treatment of pediatric patients (two years of age and older) with upper and lower limb spasticity
Date: Second quarter (exact date not given)

https://www.benzinga.com/general/biotech/19/05/13816006/attention-biotech-investors-mark-your-calendar-for-these-june-pdufa-dates

Janssen Shares Notable Prostate Cancer Data at ASCO

A little more than a year after winning regulatory approval for a non-metastatic prostate cancer treatment, Janssen Pharmaceuticals is aiming to gain approval for the same medication as a treatment for metastatic castration-sensitive prostate cancer (mCSPC).

In April, the Johnson & Johnson subsidiary announced it had submitted a supplemental New Drug Application to the U.S. Food and Drug Administration seeking approval for Erleada (apalutamide) for the aforementioned treatment of mCSPC. The sNDA is based on findings from the Phase III TITAN study, presented at the American Society of Oncology meeting today. TITAN was designed to determine whether Erleada, a selective next-generation androgen receptor inhibitor, plus androgen deprivation therapy (ADT) improves radiographic progression-free survival (rPFS) and overall survival (OS) compared with placebo plus ADT in patients with mCSPC. ADT is the backbone of treatment for this condition but the addition of supporting medications, such as Erleada has certainly improved the outcomes of care. The data from Janssen’s TITAN study is certainly impressive. And what the data shows is impressive, Joaquin Casariego Garcia Luben, J&J’s medical affairs director for prostate cancer for Europe, the Middle East and Africa, told BioSpace in an exclusive interview.

During the presentation of the abstract, Janssen showed that treatment with Erleada significantly improved (rPFS) with a reduction in the risk of death by 52 percent. Additionally, in overall survival, the TITAN data showed Erleada and ADT significantly improved OS with a 33 percent reduction in risk of death. The dual primary endpoints of the study are rPFS and OS, both of which were hit. The data showed that the combination of Erleada and ADT significantly improved radiographic progression-free survival and overall survival. The secondary endpoint of prolonged time to cytotoxic chemotherapy in patients treated with Erleada plus ADT was also met, with a 61 percent risk reduction compared with placebo plus ADT, Janssen said. Overall, the data suggests that treatment with Erleada prolongs overall survival and delays disease progression in patients with mCSPC.

Based on the trial results, the independent data monitoring committee recommended unblinding the study in order to allow those patients on placebo and ADT to receive the combination of Erleada and ADT.

“Both endpoints go together, it really shows the strength of the efficacy of this treatment,” Casariego told BioSpace in a telephone interview from Spain, ahead of his journey to ASCO in Chicago. Casariego noted that an IDMC rarely recommends unblinding a study unless the data is exceptional. He said the IDMC’s decision was made due to the “magnitude” of the results.

Janssen’s sNDA is being reviewed by the FDA through its Real-Time Oncology Review program, which for certain applications allows the FDA to review data before the applicant formally submits the complete application.

Casariego said Janssen’s goal, as well as the goal of other companies developing treatments for cancer, is to provide a treatment that can cheat death out of as many years as possible from patients.

“It’s about adding years to life, as well as life to years. This is the main challenge,” he said. “These results are promising to that. We are stealing years to death and we keep investing in research to do this.”

Prostate cancer is the second most common cancer in men worldwide, with about 164,000 expected diagnoses in the United States this year. Erleada was the first FDA-approved treatment for patients with non-metastatic castration-resistant prostate cancer (NM-CRPC). In the trial that won it the first approval, Erleada demonstrated a 72 percent reduction in risk of distant metastasis or death. Metastatic prostate cancer is cancer that has spread to another part of the body. mCSPC refers to prostate cancer that still responds to ADT. Erleada works by blocking the effect of androgens, a type of hormone, on the tumor. These androgens, such as testosterone, can promote tumor growth. Patients with mCSPC tend to have a poor prognosis, with a median OS of less than five years, which underscores the need for new treatments, Luben said.

Now 49, Casariego said he is of an age where he will begin to receive regular prostate examinations. If a doctor discovers anything that could indicate cancer, he said he is glad to know that there are an increasing number of treatment options for this disease. Any treatment, he said, that can steal time from death, is a good thing for patients.

https://www.biospace.com/article/1-janssen-to-present-titan-prostate-cancer-study-data-at-asco/

Adding BP Med to Pancreatic Cancer Treatment May Simplify Tumor Removal

A medical and research team at Massachusetts General Hospital (MGH) Cancer Center published clinical trial results of a new treatment protocol for locally advanced pancreatic cancer (LAPC). The procedure combined intensive chemotherapy and radiation with the blood-pressure drug losartan. The research was published in the journal JAMA Oncology.

Locally advanced pancreatic cancer is a type that has grown into major blood vessels and as a result, can’t be removed safety via surgery (unresectable). The cancer has not yet metastasized outside the pancreas.

“Around 40% of pancreatic cancer patients have either locally advanced or borderline resectable disease, with historically poor rates of successful surgery,”Janet Murphy told The Harvard Gazette. Murphy is co-lead and corresponding author of the study, an instructor in medicine in the hematology/oncology division of Mass General’s Department of Medicine.

“To be able to successfully remove the primary tumor in 61% of patients sets a new benchmark and offers much hope,” she added. “To our knowledge, this is the first LAPC clinical trial that defined surgical success as its primary outcome.”

The new aspect of the procedure and the study is the addition of losartan, a drug for high blood pressure that is marketed as a generic form and under the brand name of Cozaar. Earlier studies by co-author Rakesh K. Jain, director of the Steele Laboratories for Tumor Biology at MGH and Andrew Werk Cook Professor of Radiation Oncology at Harvard Medical School, found that the drug improved chemotherapy delivery in animal models of breast, pancreatic and ovarian cancer. Its method of action for this is to relieve pressure in the tumor microenvironment that actually blocks drug delivery and decreases the oxygen supply, which is necessary for the tumor-killing activity of radiation therapy. Jain’s studies also indicated that cancer patients who were otherwise taking losartan or similar hypertension medications generally lived longer than others receiving the same types of cancer therapies.

In the current study, between August 2013 and July 2017, 49 MGH Cancer Center patients who had previously been untreated for LAPC received chemotherapy with a combination of fluorouracil, leucovorin, oxaliplatin and irinotecan (FOLFIRINOX) for four months. They also took daily doses of losartan.

They then underwent CT scans to determine if the blood vessels were still involved with the tumors. Those whose blood vessels were no longer entangled received a short course of proton-beam radiation therapy. Those whose tumors still involved blood vessels received more conventional radiation therapy. Both groups continued to receive capecitabine chemotherapy during this post-CT period.

After this stage, 34 of the 49 patients had improved to where they could have their cancers removed. Thirty of the 34 patients’ cancers were successfully removed eliminating all evidence of cancer. For three patients, a pathologic complete response was observed, meaning no tumor was observed anywhere.

Biomarker studies also saw significant decreases in the expression of TGF-ß, showing that losartan was having the desired effect. Time until recurrence as well as overall survival time was significantly longer than was previously observed in LAPC patients.

“Locally advanced pancreatic cancer has been generally considered an incurable disease, so these results mark a dramatic improvement with respect both to rates of conversion to surgical resectability and to long-term disease outcomes,” co-lead author Jennifer Wo, assistant professor of radiation oncology, told The Harvard Gazette. “Based on these results we have launched a new, multi-institutional clinical trial that will also include the immunotherapy drug nivolumab [Bristol-Myers Squibb’s Opdivo), since losartan treatment has also been shown to activate several immune-system pathways.”

https://www.biospace.com/article/mass-general-tests-new-approach-to-pancreatic-cancer/

Search This Blog

Saturday, June 1, 2019

Merck Seeks Approval For Expanded Indication For Antibiotic

Xeris’ Glucagon Autoinjector For Low Blood Sugar

Can Merck Snatch Another Approval For Keytruda?

Merck’s Keytruda For Lung Cancer

Palatin’s Drug For Hypoactive Sexual Desire Disorder Awaits

Acer Seeks Approval For Drug To Treat Rare Genetic Disease of Connective Tissue

Can Dupixent Get The Nod For Expanded Indication?

Can Alexion’s Soliris Pass The Muster For NMOSD?

Retrophin Awaits FDA Nod For New Formulation Of Rare Kidney Disorder Drug

Dova’s Bleeding Disorder Drug On Course For Snagging Another Approval

Allergan Seeks Label Expansion For Botox