FDA chief outlines new ways to speed cancer drug approvals: #ASCO18

The U.S. Food and Drug Administration is taking steps to streamline the approval process for cancer drugs, reviewing clinical trial data up front to make sure applications companies submit are complete.

The new approach, outlined on Saturday in a speech by FDA commissioner Dr. Scott Gottlieb at the American Society of Clinical Oncology (ASCO) meeting in Chicago, is part of an effort to remove regulatory barriers that drag out reviews of promising new cancer treatments.

The new review process, which Gottlieb called a “real-time oncology review,” is already being piloted in a number of applications for expanded use of already approved cancer drugs. Gottlieb believes the early peek at data would allow companies to address quality issues before submitting their the full application seeking approval.

If the process succeeds, it will be expanded to applications for new cancer treatments.

As part of the pilot program, FDA is trying out a shared application document that allows FDA reviewers to add their comments to background documents submitted by companies.

The FDA is also taking steps to streamline and standardize the review of manufacturing processes for gene therapies and cell based products, such as new chimeric antigen receptor T-cell therapies, or CAR-Ts, which involve removing and altering patients’ immune cells to recognize and attack cancer.

Gottlieb said such a move could enable more sites, such as hospitals or research facilities, to manufacture these cells, expanding treatment options for patients. Currently, harvested T-cells are shipped back to the companies for processing, and it takes about three weeks before the cells are returned and administered to patients.

FDA also plans to expand its database on the long-term safety issues related to CAR-T therapy to more than 1,000 patients by later this summer. The information will be used to study potential biomarkers that can predict long-term remission.

https://reut.rs/2J9C2Sj

Roche drugs show limited benefit in lung, breast cancer trials

In a disappointment for Roche Holding AG (ROG.S), two of its oncology drugs provided only modest protection from disease progression in lung cancer and breast cancer, according to data from separate clinical trials presented on Saturday.

Adding Roche’s high-profile immunotherapy Tecentriq to other standard cancer drugs extended by only about three weeks the median time patients with advanced squamous cell lung cancer lived before their disease progressed in one late stage study.

Meanwhile, Roche said it was scrapping development plans for its experimental drug taselisib after data showed adding it to hormone therapy extended by just two months the length of time women with advanced breast cancer lived before their disease worsened. Patients on the drug also experienced serious side effects.

The taselisib benefit to patients “was more modest than we had hoped for, and there is a risk of considerable side effects,” said Dr. José Baselga, the study’s lead investigator from Memorial Sloan Kettering Cancer Center in New York.

Roche in a statement also said the results were disappointing, adding “we will not be pursuing an FDA submission for taselisib based on the data presented at ASCO.”

The company also said it had no plans to further test taselisib in other types of cancer.

Both studies were being presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago. For more coverage of the meeting, see: here

Sales of Roche’s Tecentriq trail two rival lucrative therapies that also spur the body’s immune system to attack tumors: Keytruda from Merck & Co (MRK.N) and Opdivo from Bristol-Myers Squibb (BMY.N). Roche is under pressure to show success for the drug, which is central to replacing falling revenue from older, off-patent medicines.

Tecentriq is already approved for previously treated patients with advanced non-small cell lung cancer (NSCLC) and certain patients with advanced bladder cancer. Analysts are forecasting annual Tecentriq sales reaching about $6 billion by 2024, according to Thomson Reuters data.

Roche said it will continue to evaluate results from the study presented on Saturday.

“The study is one of eight Phase III trials from our extensive research program evaluating Tecentriq alone or in combination with other medicines in different types of lung cancer,” Roche said in a statement.

Merck’s Keytruda, in combination with chemotherapy, is approved as an initial treatment for non-squamous NSCLC, the most common form of lung cancer. Keytruda is also approved as a stand-alone treatment for lung cancer patients whose tumors have high levels of a protein known as PDL1.

The new Tecentriq trial studied 1,021 patients with late-stage squamous NSCLC, which accounts for about 30 percent of lung cancer and is considered particularly difficult to treat.

Roche Holding AG215.95

ROG.SVIRT-X LEVEL 1

+4.90(+2.32%)

• ROG.S
• MRK.N
• BMY.N
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One group of patients received the Roche drug plus the chemotherapy carboplatin and Celgene Corp’s (CELG.O) Abraxane, while a second group were only treated with carboplatin and Abraxane.

After 12 months, 25 percent of patients given the Tecentriq combination had not experienced disease progression compared with 12 percent in the chemotherapy group, Roche said.

But median progression-free survival was 6.3 months for Tecentriq patients versus 5.6 months for the standard chemotherapy combination.

The modest benefit was observed regardless of tumor PDL1 levels, researchers said. The analysis did not find an overall survival advantage with Tecentriq, although Roche said those data are not yet mature.

Merck last month said a study of Keytruda in combination with chemotherapy for squamous NSCLC showed a benefit in both overall survival and progression-free survival. [nL3N1SU48D]

In the study of taselisib, patients who received the Roche drug plus the hormone therapy fulvestrant saw their breast cancer worsen after a median of 7.4 months compared with 5.4 months for people who received fulvestrant alone.

The trial involved 516 postmenopausal women with advanced estrogen receptor-positive breast cancer, whose disease had progressed or returned after prior treatment.

Serious side effects in the taselisib group included diarrhea, high blood sugar and colon inflammation, leading 17 percent of treated patients to drop out of the trial.

https://reut.rs/2HeEbGx

Parkinson’s: ‘Adaptive’ brain implant may improve therapy

Parkinson’s, a neurodegenerative condition, is characterized by symptoms such as muscle stiffness and tremor in the limbs, as well as impaired balance, all of which tend to worsen over time. Has innovative research found a more reliable tool that helps to improve these symptoms?

An adjustable new brain stimulation implant could bring Parkinson’s therapy to a whole new level.

The National Institutes of Health (NIH) report that approximately 50,000 individuals in the United States receive a Parkinson’s diseasediagnosis every year.

Available treatments for this condition target its symptoms, aiming to improve the patients’ quality of life.

These treatments include different types of drugs that may focus either on motor on non-motor effects of the disease, as well as deep brain stimulation, which may be offered as an alternative therapy to people who do not respond well to drugs.

In deep brain stimulation, electrodes are surgically implanted into the brain. These are connected to a device that is attached to the chest. Through these implants, electrical stimuli are transmitted to the regions of the brain that regulate movement.

However, deep brain stimulation has — at least so far — come with certain risks and drawbacks. The device works continuously and has to be programmed so that the stimuli it sends are best adjusted to the wearer’s needs.

Often, devices will need to be reprogrammed by a specialist. Also, because they run on batteries, the lifespan of these implants is limited, and they eventually have to be replaced.

A team from the National Institute of Neurological Disorders and Stroke — led by specialist Nick B. Langhals — recognizes these drawbacks and set out to test more personalizable deep brain stimulation implants.

The results of their efforts — which were part of the Advancing Innovative Technologies (BRAIN) Initiative — have been reported in the Journal of Neural Engineering.

A new type of brain stimulation implant

Langhals and team tested a type of implant that responds and adjusts to signals from the brain that are related to the symptoms experienced in Parkinson’s disease. Not only does it register these inputs, but in doing so, it also adapts to deliver appropriate stimulation as needed.

“This is the first time,” explains senior study author Dr. Philip Starr, that “a fully implanted device has been used for closed-loop [non-constant], adaptive deep brain stimulation in human Parkinson’s disease patients.”

The project was a short-term feasibility trial, in which two people with Parkinson’s agreed to receive this fine-tuned, adaptable deep brain stimulation implant.

In this trial, the implant was programmed to monitor the brain for signals related to dyskinesia — or involuntary movements — which sometimes occurs as a side effect of deep brain stimulation.

So, when the device picked up signs of dyskinesia, it reduced stimulation to the brain. On the other hand, when no dyskinesia was detected, the stimulation was increased. This strategy was calculated to decrease the side effects related to this type of therapy.

The trial’s results indicated that this type of implant was no less effective in reducing Parkinson’s symptoms than traditional deep brain stimulation.

Also, since this device is adaptive and does not send out stimuli constantly, the researchers noted that it saves approximately 40 percent of the battery energy that would normally be consumed during traditional, open-loop brain stimulation.

Because these tests were only carried out over a short period of time, it was not possible for the investigators to establish exactly how the innovative implant performed, compared with more traditional brain stimulation devices, when it comes to instances of dyskinesia.

However, due to the new implant’s adaptability, the researchers are hopeful that the closed-loop stimulation device would fare much better in this respect and possibly lead to fewer adverse effects.

‘An important first step’

Also, Dr. Starr explains, “Other adaptive deep brain stimulation designs record brain activity from an area adjacent to where the stimulation occurs, in the basal ganglia, which is susceptible to interference from stimulation current.”

“Instead,” he goes on, “our device receives feedback from the motor cortex, far from the stimulation source, providing a more reliable signal.”

The researchers are excited about the avenues that this feasibility study is opening up in terms of improving Parkinson’s therapy, and they are already planning larger trials in order to test the device’s long-term effectiveness.

“The novel approach taken in this small-scale feasibility study may be an important first step in developing a more refined or personalized way for doctors to reduce the problems patients with Parkinson’s disease face every day.”

Nick B. Langhals

https://bit.ly/2kI1MXm

Sarah Cannon/HCA at #ASCO18

Sarah Cannon announced that it will present its latest cancer research insights through more than 85 presentations at the American Society of Clinical Oncology’s (ASCO®) Annual Meeting. Hosted in Chicago, from June 1-5, 2018, the ASCO® Annual Meeting is bringing together global oncology leaders to discuss “Delivering Discoveries: Expanding The Reach of Precision Medicine.” Sarah Cannon experts will participate in a number of presentations and educational sessions focused on personalized medicine and targeted investigational therapies that are transforming the current and future state of cancer treatments.

“Sarah Cannon’s 25-year history has been highlighted by leading in a number of innovative areas of clinical research,” said Howard A. “Skip” Burris, III, MD, President of Clinical Operations and Chief Medical Officer at Sarah Cannon. Dr. Burris will also serve as the ASCO® President for the 2019-2020 term. “From novel antibodies to targeted biologics, and now advancements in the field of cellular therapies, we are bringing cutting-edge treatments to patients closer to home.”

As part of ASCO®’s Meeting focus, Sarah Cannon’s leaders will participate in the following highlighted sessions:

• A presentation with Dr. Burris, who will discuss “Most Patients Should Be Tested” in the education session “Point/Counterpoint: Next Generation Sequencing – Is It Right for Every Patient?” which will take place on June 1 from 1:20-1:40pm in S102.
• A “Best of ASCO®” clinical science symposium titled “A Phase 1 Study of LOXO-292, A Potent And Highly Selective RET Inhibitor, In Patients With RET-Altered Cancers” featuring Sarah Cannon co-authors Todd Bauer, MD, and Melissa Johnson, MD, as part of the session “Tumor Genomics: Finding The Target, Hitting The Target” on June 2 from 8-9:30am in Hall D1.
• A poster presentation by Stephanie Graff, MD, titled “Implementation of Breast Cancer Pathway For Genetic Counseling And Testing In Multi-State Health System” as part of the session “Health Services Research, Clinical Informatics, and Quality of Care,” on June 2 from 1:15-4:45pm in 6521 Hall A.
• A poster presentation by Holli Dilks, PhD, and Andrew McKenzie, PhD, titled “Identifying And Interpreting Actionable Molecular Alterations From Next-Generation Sequencing Results In The Community: A Sarah Cannon Molecular Cancer Conference” on June 2 from 1:15-4:45pm in 6601 Hall A.
• A poster session by David Moore, MD, titled “Routine Use of A Modest Next Generation Sequencing Panel Provides Additional Clinically Useful Data Beyond Single Gene Testing In Non-Small Cell Lung Cancer And Is Fit For Purpose As A Clinical Assay: Collated Data From A Single Molecular Diagnostic Laboratory” on June 3 from 8-11:30am in 8540 Hall A.

Additionally, Sarah Cannon investigators are presenting noteworthy studies and insights at ASCO® with the following presentations:

• Dr. Burris’ poster session on “Maintenance Of Health-Related Quality Of Life In Elderly Patients Treated With Ribociclib + Letrozole In MONALEESA-2” taking place on June 2 from 8-11:30am in 1041 Hall A.
• A poster session by Erika Hamilton, MD, titled “Results from a Phase I Study of Andecaliximab In Combination With Paclitaxel In Patients With Previously Untreated Metastatic Breast Cancer,” on June 2 from 8-11:30am in 1032 Hall A. Dr. Hamilton will also highlight research on “Phase 1 Dose Escalation Of XMT-1522, A Novel HER2-Targeting Antibody-Drug Conjugate, In Patients With HER2-Expressing Breast, Lung And Gastric Tumors” in a poster session on June 4 from 8-11:30am in 2546 Hall A.

• A poster session with Kent Shih, MD, on “Dianhydrogalactitol In Bevacizumab-Refractory GBM: Further Analysis Of A Phase 1-2 Trial,” on June 2 from 1:15-4:45pm in 2061 Hall A.
• A poster discussion by Dr. Bauer titled “A Phase 1 Study of MDM2 Inhibitor DS-3032b In Patients With Well/De-Differentiated Liposarcoma, Solid Tumors And Lymphomas” on June 2 from 3-4:15pm in S404.
• A poster session by Dr. Johnson on “First In Human Phase 1/2a Study of PEN-221 Somatostatin Analog (SSA)-DM1 Conjugate For Patients With Advanced Neuroendocrine Tumor Or Small Cell Lung Cancer: Phase 1 Results” on June 3 from 8-11:30am in 4097 Hall A. Dr. Johnson will also present a poster on “A Phase I, Open-Label, Multicenter Dose Escalation Study To Assess The Safety, Tolerability, And Pharmacokinetics Of AZD2811 Nanoparticle In Patients With Advanced Solid Tumors” on June 4 from 8-11:30am in 2592 Hall A.
• An education session with David Spigel, MD, on “Reimbursement And Payment Of Multiplex Testing In The United States” taking place on June 3 from10:15-10:30am in S100a.
• An education session with Dr. Graff on “How Close Is Too Close: Navigating Difficult Situations” as part of the session titled, “When Cancer Hits Close to Home: Treating Colleagues and Loved Ones” on June 4 from 8:30-8:45am in S504.

• A poster session by Judy Wang, MD, titled “Interim Results From A Phase 1 Trial Of SL-801, A Novel XPO-1 Inhibitor, In Patients With Advanced Solid Tumors” on June 4 from 8-11:30am in 2560 Hall A.
• A poster session by Manish Patel, MD, titled “A Phase 1b Dose-Escalation Study Of Prexasertib, A Checkpoint Kinase 1 (CHK1) Inhibitor, In Combination With Cisplatin In Patients With Advanced Cancer” on June 4 from 8-11:30am in 2579 Hall A.
• A poster session by Kathleen Moore, MD, on “Phase 1/2 Open-Label, Multiple Ascending Dose Trial of AGEN2034, An Anti-PD-1 Monoclonal Antibody, In Advanced Solid Malignancies: Results Of Dose Escalation” on June 4 from 8-11:30am in 3086 Hall A.

For a full listing of all presentations authored by Sarah Cannon investigators, visit sarahcannon.com/asco.

Additional Sarah Cannon leaders are co-authors on research presented at the conference, including:

Bertrand Marquess Anz, Raid Aljumaily, MD, Hendrik-Tobias Arkenau, MD, PhD, FRCP, Edward Arrowsmith, MD, Johanna Bendell, MD, Jesus Berdeja, MD, Brook Blackmore, Simon Chowdhury, MA, MRCP, PhD, Mick Correll, Brooke Daniel, MD, Davey Daniel, MD, William Bruce Donnellan, MD, Crystal Dugger, James Essell, MD, Gerald Falchook, MD, MS, Gustavo Fonseca, MD, FACP, Ian Flinn, MD, PhD, Troy Gifford, Lowell Hart, MD, Derek Weldon Holland, MD, Suzanne Jones, PharmD, Darrell Johnson, MD, Sylvia Lynne Krueger, MD, Dax Kurbegov, MD, Andrew Mackenzie, PhD, Michael Maris, MD, Jeffrey Matous, MD, Carmen Murias, MD, Benjamin Rolland Nadeau, MD, Michael Stipanov, MD, DK Strickland, MD, An Tran, MD, Kimberly Tucker, and Denise Yardley, MD.

The researchers represent Sarah Cannon’s global network of strategic sites:

Colorado Blood Cancer Institute, Sarah Cannon Research Institute at Florida Cancer Specialists, Sarah Cannon Research Institute at HCA Midwest Health (Kansas City), Sarah Cannon Research Institute at HealthONE (Denver), Sarah Cannon Research Institute at Tennessee Oncology, , Sarah Cannon Research Institute – United Kingdom, and The Stephenson Cancer Center at the University of Oklahoma

About Sarah Cannon Research Institute

Sarah Cannon Research Institute is the research arm of HCA Healthcare’s global cancer institute, Sarah Cannon. For 25 years, the organization has focused on advancing therapies for patients and has become one of the world’s leading clinical research organizations conducting community-based clinical trials throughout the United States and United Kingdom. Sarah Cannon’s network of strategic sites includes more than 275 physicians who engage in research. The organization has led more than 300 first-in-man clinical trials since its inception in 1993, and has been a clinical trial leader in the majority of approved cancer therapies over the last 10 years. Additionally, Sarah Cannon offers management, regulatory, and other research support services for drug development and industry sponsors as well as strategic investigator sites through its contract research organization (CRO), Sarah Cannon Development Innovations. For more information, visit sarahcannon.com.

https://bit.ly/2J4nJhL

#ASCO18: 1/2 Novartis treated leukemia ex-patients still in remission after 3 yrs

• ENESTop and ENESTfreedom data evaluate Treatment-free Remission (TFR) rates at 144 weeks among eligible Ph+ CML-CP patients who stopped Tasigna^® 
• Findings further support durability and safety of TFR with Tasigna; nearly all patients who lost TFR regained major molecular response after restarting therapy
• Novartis commitment to seek new solutions in CML continues with update of Phase III trial evaluating asciminib, an investigational BCR-ABL1 inhibitor

New Novartis data from two long-term Treatment-free Remission (TFR) studies in patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase (CP) will be presented during the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Results from the open-label Phase II trials, ENESTop and ENESTfreedom, show sustained TFR in patients treated with both front-line and second-line Tasigna^® (nilotinib) therapy. The 144-week trials evaluate the potential to maintain molecular response (MR) after stopping therapy in eligible adult patients with Ph+ CML-CP.

“Treatment-free Remission is a new treatment goal in CML,” said François-Xavier Mahon, Cancer Center of Bordeaux, Institut Bergonié and lead investigator of ENESTop. “Clinical studies like ENESTop and ENESTfreedom offer evidence that when a Ph+ CML-CP patient achieves a deep molecular response with Tasigna, along with other eligibility criteria, s/he can attempt TFR and have a nearly 50% chance of remaining treatment-free long-term. These results confirm an exciting opportunity for eligible patients – the opportunity to reduce time on drug for a chronic leukemia.”

Data from ENESTop, presented today in an oral session (Abstract #7003) show that approximately half (48.4%; CI 95%, 39.4%-57.5%) of patients with Ph+ CML-CP who are eligible to stop second-line Tasigna therapy maintained disease remission over a prolonged period of time in the absence of treatment at 144 weeks of follow up, almost 3 years[1]. Patients in this trial took Tasigna following a switch from Glivec^® (imatinib)*. ENESTop data also show that of the patients who restarted Tasigna due to loss of major molecular response (MMR=BCR-ABL/ABL <=0.1% IS), during the study period, nearly all (97.1%) regained MMR and 95.8% regained MR^4.5(BCR-ABL1 IS =< 0.0032%)[1]. Study authors stress that frequent scheduled and compliant monitoring is necessary to assess for loss of response. Results of ENESTop at 144-weeks are consistent with previously reported data at both 96- and 48-weeks.

A second long-term clinical trial, ENESTfreedom, is also part of the ASCO Scientific Program this week. The authors will report on TFR results at 144 weeks in patients who started front-line CML therapy with Tasigna. Results from ENESTfreedom will be shared with ASCO attendees on Monday, June 4 (Abstract #7063). In this trial, researchers found that almost half (46.8%; CI 95%: 39.6%-54.2%) of Ph+ CML-CP patients eligible to stop Tasigna treatment remained in MMR following treatment discontinuation[2].

“Novartis continues to redefine treatment options for Ph+ CML patients,” said Samit Hirawat, MD, Head of Novartis Oncology Global Drug Development. “The importance of achieving deep and sustained responses with Tasigna has been demonstrated in our TFR clinical program, which is the largest among all oncology companies. These long-term trials deliver on our commitment to the patient community to continue to look for more and better solutions for CML.”

An update on the Phase III clinical trial design for Novartis’ investigational BCR-ABL1 inhibitor, asciminib, will also be presented as part of the ASCO Scientific Program (Abstract #TPS7081).

https://bit.ly/2Lj87Up

Employers urge Trump administration to pull back on Obamacare mandate

The employer mandate — the only Obamacare tax Congress did not repeal or delay this year — has business groups urging the Trump administration to pull back from trying to collect as much as $4.3 billion from companies that are now on the hook for assessments.

Companies have cried foul about the tack the Internal Revenue Service has taken to collect the assessments, arguing that they weren’t given proper warning or due process and that the administration has violated clear provisions in the Affordable Care Act that outlined how the mandate should be enforced.

A broad coalition that includes the U.S. Chamber of Commerce and the National Retail Association argued in a letter to top officials that the “administration’s enforcement efforts violate the ACA’s express guarantee that employers be given ‘two bites of the apple’ before tax penalties can be assessed.”

They said the “cost, complexity and confusion surrounding compliance with the employer mandate” warrants suspension of the notice letters the IRS continues to send out.

Last fall, the agency began to warn employers via letter that they owed penalties for the 2015 calendar year. The letters continued while GOP-led Congress began to signal they would at least temporarily lift most of the other Obamacare levies such as the Cadillac Tax and health insurance tax. Congress even effectively eliminated the individual mandate penalty as the IRS sent at least 10,000 assessment letters to employers.

The agency estimates that more 30,000 companies owe money, according to testimony this April before the House Oversight and Government Reform Committee.

In one assessment letter obtained by Modern Healthcare last year, the IRS said the company in question needed to pay more than $3.8 million and allowed 30 days to respond with the money owed or evidence that the agency assessed an incorrect penalty.

Companies have been weighing legal action since late last year, and legal consultant Christopher Condeluci ,who has been advising business groups on the issue, said they continue to do so.

Although Congress hasn’t made a move to delay or repeal the employer mandate,House lawmakers last week proposed to delay the health insurance tax again until 2021.

https://bit.ly/2J7mAGe

CMS considers paying for medical device that treats depression

The CMS is considering paying for a type of brain stimulation therapy for Medicare beneficiaries suffering from treatment-resistant depression.

Vagus nerve stimulation (VNS) therapy involves implanting a battery-powered neurostimulator in a patient’s skull to send mild pulses of electrical energy to the brain.

VNS therapy costs up to $30,000 per person in the U.S., according to Inkwood Research, a Boston-based research firm. This includes the cost of the device itself, surgery and other hospital charges.

As many as 5 million people have treatment-resistant depression, according to the National Institute of Mental Health.

The CMS had previously paid for VNS in depression patients starting in 1999. But the agency eliminated the coverage in 2007 due to insufficient evidence showing VNS successfully treated their symptoms.

LivaNova, a medical device company that manufactures a VNS product, sent a formal request for coverage late last year. It cited a March 2017 study published in the American Journal of Psychiatry that showed patients with treatment-resistant depression who were treated with vagus nerve stimulation as well as medication and therapy had better outcomes than those who received just drugs and therapy.

“These patients are in desperate need of treatment options and we believe that the weight of scientific evidence provided in this formal request for reconsideration supports coverage of VNS therapy as a treatment option,” LivaNova officials said in a letter.

The CMS will accept comments on the request until June 29. It plans to issue a proposed decision by November and finalize its decision by next February.

https://bit.ly/2srQ8nI