New Cancer Patients Often Unaware of HBV/HCV Infection

A substantial proportion of newly diagnosed cancer patients were unaware they were concurrently infected with hepatitis B virus (HBV), hepatitis C virus (HCV) or, less frequently, HIV, placing them at risk for serious adverse complications when treated with chemotherapy or other anti-cancer strategies, a SWOG Cancer Research Network study showed.

Out of a cohort of 3,051 newly diagnosed cancer patients, 6.5% (95% CI 5.6%-7.4%) had been previously infected with HBV, 87.3% (95% CI 81.8%-91.6%) of whom were diagnosed with HBV only at the time of study registration, Scot Ramsey, MD, PhD, of Fred Hutchinson Cancer Research Center in Seattle, and colleagues found.

Another 0.6% of patients (95% CI 0.4%-1.0%) had chronic HBV infection — 42.1% (95% CI 20.3%-66.5%) of whom had not been diagnosed prior to study entry.

As shown in the study online in JAMA Oncology, among a slightly smaller group of the same patients, 2.4% (95% CI 1.9%-3.0%) were HCV-positive — 31.0% (95% CI 20.5%-43.1%) of whom were unaware of their viral status on study entry.

HIV infection rates were lower, at only 1.1% (95% CI 0.8%-1.6%) in the overall cohort, but here again, 5.9% did not know their viral status at the time of study registration. The rates of HBV and HCV infection found in the study cohort were actually quite similar to rates found in the U.S. population as a whole, the researchers noted.

“The results of this study showed that a substantial proportion of patients with newly diagnosed cancer and concurrent HBV or HCV are unaware of their viral infection at the time of cancer diagnosis,” the researchers wrote. “Screening patients with cancer to identify HBV and HCV infection before starting treatment may be warranted to prevent viral reactivation and adverse clinical outcomes.”

Asked for his perspective, Harrys Torres, MD, of the University of Texas MD Anderson Cancer Center in Houston, agreed, noting that his institution had started screening all patients with hematologic malignancies for HBV and HCV about 10 years ago, because when started on chemotherapy, patients were at risk for complications related to reactivation of either virus which in some cases can be fatal.

A study led by his colleague Jessica Hwang, MD, also found that the majority of a large cohort of patients with solid and hematologic malignancies still required HBV testing if the goal is to achieve a false-negative rate of zero.

Similarly, another 2018 study by the group found that if HCV screening of newly diagnosed cancer patients is limited to the high-risk baby boomer birth cohort, many patients would be left with undiagnosed HCV infection, since many of the affected patients in the current study were not baby boomers, nor did they have risk factors for HCV. “For me, this important study is a prospective validation of our initial observations,” Torres told MedPage Today.

“Patients with HBV or HCV can present with any type of cancer — not just liver cancer but breast, prostate, and head and neck — and we have to identify these patients when they present because not only might they receive bone marrow transplantation or even rituximab, both of which can reactivate HBV and even HCV, but also we don’t yet know what any of the new cancer drugs are going to do in patients with HBV or HCV and these drugs could lead to other complications,” he suggested.

Lastly, the presence of either viral infection could prompt oncologists to err on the side of caution and offer patients a less effective treatment plan out of concern that concurrent HBV or HCV might lead to unwanted complications. This is particularly concerning, Torres noted, because HBV is treatable and HCV is potentially curable — and once the viral infections are treated, oncologists can proceed to treat patients as they optimally should be.

“Even if patients do have a viral infection, if we can eliminate that from the picture, patients can move on and receive the cancer treatment they need,” Torres emphasized.

For the current study, Ramsey and colleagues recruited patients from nine academic and nine community oncology institutions affiliated with SWOG and tested them for the presence of HBV, HCV, or HIV infection on study enrollment. About 60% of the patients were women; about 18% of the cohort were black, and another 18% were Hispanic.

“Previous HBV infection risk was highest in those who had sexual contact with HIV-positive persons, or who were born in high HBV-prevalence regions,” the team added.

HCV infection rates were also predictably highest among injection drug users, while the risk of HIV infection was highest in patients who had sexual contact with other HIV-positive persons. However, as the authors noted, many patients identified as having HBV, HCV, and HIV infection in the current study had no known risk factors.

This underscores, as Torres said he himself has found, the futility of using a risk-based screening strategy which would miss substantial proportions of infected patients who, unaware of their viral status, could pose a transmission risk to family and healthcare workers alike.

“As a cancer patient, or physician, I would want to know the results of a hepatitis screening test,” Ramsey said in a statement. “The presence of a potentially life-threatening infection could guide care in very important ways. In medicine, more knowledge is always better.”

Ramsey reported having no financial conflicts of interest to declare.

Torres reported financial relationships with Gilead Sciences, Merck, and Dynavax.

• Primary Source

  JAMA Oncology

  Source Reference: Ramsey S, et al “Prevalence of hepatitis B virus, hepatitis C virus, and HIV infection among patients with newly diagnosed cancer from academic and community oncology practices” JAMA Oncol 2019; DOI: 10.1001/jamaoncol.2018.6437.

https://www.medpagetoday.com/hematologyoncology/othercancers/77504

FDA Advisory Committee Split on Sanofi SGLT 1/2 Inhibitor for T1D

An FDA advisory committee is split down the middle on whether to recommend the SGLT-1/2 inhibitor sotagliflozin (Zynquista) for approval.

In a vote of 8-8, members of the Endocrinologic and Metabolic Drugs Advisory Committee couldn’t reach a consensus whether or not the benefits outweighed the risks of Sanofi’s investigational drug, which the drugmaker wants OK’d as an add-on to insulin therapy in patients with type 1 diabetes.

Calling this “a very difficult decision,” Jack Yanovski, MD, PhD, of the National Institute of Child Health and Human Development in Bethesda, said that he didn’t think the drug was “ready for prime time” despite its advantages.

“I think there are additional studies that need to be done before this is released on a wider public,” he said, specifically pointing out a need for data to support a risk evaluation and mitigation strategy for reducing diabetic ketoacidosis (DKA) with the drug. Clinical trial data had shown an 8-fold increase in DKA risk relative to placebo.

After voting “yes,” Rebecca Brown, MD, of the National Institute of Diabetes and Digestive and Kidney Diseases, said she expected “a subset of patients for whom the benefits of this drug will outweigh the risks, but that’s certainly not going to be true for every patient.”

Some members who voted yes said this vote hinged on future research on risk reduction and monitoring strategy for reducing DKA. Many members who voted yes also only voted for a dose of 200 mg to be recommended for approval, rather than the 400-mg dose also tested.

If approved, this would be the first oral therapy indicated for adults with type 1 diabetesas an adjunct to insulin therapy. Dosage of the once-daily oral therapy is recommended in a 200 mg dose before the day’s first meal; Sanofi proposed that it could then be increased to 400 mg once daily if well-tolerated in patients not yet achieving glycemic control.

Throughout Thursday’s meeting, efficacy of the drug was only lightly debated, as the risk of DKA served as the main topic of discussion. As efficacy was established through a phase III clinical program, including three safety and efficacy studies, superiority of sotagliflozin was reported in all studies when compared with placebo for a significant reduction in HbA1c levels — a drop ranging from 0.3% to 0.45% after 24 weeks of adjunct treatment. Although the reduction in HbA1c levels was significant at both doses tested — 200 mg and 400 mg — the magnitude of benefit was slightly greater at the higher dose. This was also paired with a reduction in body weight seen with the drug, as well as higher patient satisfaction with the treatment regimen.

However, both doses were also accompanied by an increased risk for DKA, which served as the main topic of debate throughout the meeting.

“While all patients with type 1 diabetes may to some degree be at risk for DKA, sotagliflozin therapy clearly increases that risk, and the risk may be unpredictable,” noted FDA briefing documents.

In order to mitigate it, Sanofi proposed educational materials and patient leaflets on DKA risks. The firm also suggested blood or urine ketone monitoring of patients on the drug, and following the STICH protocol: hydration, carbohydrate intake, insulin, and calling a healthcare provider.

During a more than hour-long public comment period, the panel heard from healthcare providers arguing both sides. Advocates for approval pointed to a lack of effective treatment options in addition to insulin for type 1 diabetes. Some also offered successful anecdotal evidence of using SGLT-2 inhibitors off-label in patients with type 1 diabetes, while others offered strategies for reducing DKA risk, including daily ketone monitoring. But others argued that the DKA risk is an insurmountable hurdle. (In a Thursday press release, the consumer group Public Citizen took the latter view and urged rejection of the drug.)

Prior to the vote when the panel was discussing the risk/benefit profile, the potential for reducing microvascular complications — although there were no data on this — seemed to sway some of the members. Weight loss was also brought up several times during discussion as a major benefit tipping the scales in favor of sotagliflozin. Despite many panel members calling the HbA1c benefit modest, some suggested other benefits such as time in range would make the drug’s overall benefit in real-world practice even greater.

But the DKA issue hung over panel members all day. Several voiced doubts over whether patients would adhere to the risk mitigation strategy proposed by Sanofi, with many noting the sponsor didn’t actually provide hard proof that it works. The increased risk for genital mycotic infections, seen with other SGLT-2 inhibitors, also raised concerns among members.

“I think it’s impossible to understate the concern about DKA really just because the absolute increase is really remarkable,” stated Michael Blaha, MD, of Johns Hopkins Ciccarone Center for the Prevention of Heart Disease in Baltimore. “I am concerned about the prospect that this could be worse in the real world [outside of the trial setting].”

“One thing I was surprised to see is very little data presented by the sponsor, at least right now, about proof that the risk-management strategy works or the best way to do it. It would be great if we had that data before we approved a drug — say this is the best risk strategy rather than figuring it out later when patients are at risk,” he continued. He added, however, that the drug appears beneficial.

Another topic of discussion was differentiating between the two proposed doses: 200 mg versus 400 mg.

“I am not convinced that it makes any sense to go beyond the 200 mg,” said Marvin Konstam, MD, of Tufts Medical Center in Boston, citing the increased DKA risk at the 400-mg dose as his reasoning. “There’s no great difference in terms of glycemic control.”

In response, Brown said the drug’s serum levels vary with body weight. “What we’re looking for with the 400-mg dose is an effect comparable to the 200-mg dose in a smaller individual.”

Although the FDA is not required to follow its advisory committees’ recommendations, it typically does. However, split votes are generally taken as no recommendation one way or the other.

https://www.medpagetoday.com/endocrinology/type1diabetes/77508

Lilly’s Verzenios approved by NICE

NICE has published draft guidance that now recommends Eli Lilly’s breast cancer drug Verzenios for use on the NHS.

The guidance concludes that Verzenios (abemaciclib) is as effective as its rivals, Pfizer’s Ibrance (palbociclib) and Novartis’ Kisqali (ribociclib), which NICE approved in 2017 for treating hormone receptor-positive, HER2‑negative, locally advanced or metastatic breast cancer as initial hormone therapy.

The three drugs are part of a new therapy class called CDK4/6 inhibitors. These are taken with an aromatase inhibitor, a type of anti-cancer drug which blocks the production of the hormone oestrogen, preventing it from stimulating the growth of some breast cancers. CDK4/6 inhibitors work by increasing the effect of aromatase inhibitors.

Ibrance has become the market leader by virtue of being the first approved, and is now Pfizer’s biggest selling cancer drug, with sales approaching $2 billion in the first six months of last year.

NICE rejected Verzenios in October last year, saying that it was not cost effective compared to its rivals when patient access schemes were taken into account – but has changed its mind now that an ‘improved’ scheme has been agreed.

Data from Lilly’s pivotal MONARCH trial shows the drug is likely to be as effective as its rivals, however a high incidence of diarrhoea and neutropenia could make it less attractive to doctors and patients than its competitors.

In the US Lilly gave Verzenios a slightly lower price than Kisqali in an attempt to compensate for this.

In the UK the list price of abemaciclib, which is given as a 150 mg tablet twice daily, is £2,950 for a 58 tablet pack of 150 mg tablets – but as with Ibrance and Kisqali a confidential discount has been agreed.

Lilly was also hoping that the drug could be used in lung cancer patients with a KRAS mutation, but a late-stage trial failure means that the company may have lost out on this indication.

Around 46,000 women are diagnosed with breast cancer each year in England and Wales, of whom Lilly estimates approximately 8000 would be eligible for treatment with abemaciclib.

https://pharmaphorum.com/news/lillys-verzenios-approved-nice/

Telehealth firm secures more cash to expand in China, Japan and US

Telehealth firm Tyto Care has secured additional funding to help with the launch of its technology allowing for remote medical examinations.

This latest $9 million funding round is an extension of an oversubscribed Series C round last year and brings the total funds raised to $33.5 million.

Strategic investors including Sanford Health, Itochu and Shenzhen Capital Group and affiliates have backed Tyto, which aims to use remote telehealth technology to improve access to healthcare and delivery in the US, Japan and China.

Tyto hopes the technology will be used with patients in densely populated regions of these countries, but also in rural US, Chinese and Japanese communities with limited access to clinicians and specialists.

The company’s product was approved in the US in 2017 and in Canada in 2018, and Tyto wants to build its presence in state health systems, telehealth companies, large private practices and employers.

Tyto said the funding will enable the company to grow and penetrate new markets beyond North America, including Asian and European markets.

Tyto Care’s technology is designed to enable a comprehensive medical exam from any location and include a hand-held modular tool for examining the heart, lungs, skin, throat, ears, and body temperature.

The platform allows sharing of exam data, video exams and visit scheduling, a clod-based data repository with analytics, and built-in guidance technology and machine learning algorithms to ensure accuracy and ease of use.

It can also be integrated with other e-health record systems and telehealth platforms.

Dedi Gilad, CEO and co-founder of Tyto Care, said: “This additional funding is a testament to the value of telehealth in the digital age, further enabling our unique solution to bring the best of remote, on-demand virtual care to consumers around the world.”

Chairman Zewang Ni of Shenzhen Capital Group, said: “We believe that telehealth will significantly improve the lives of Chinese consumers, whether they are parents with sick children at home, elderly patients facing chronic illnesses, or citizens living in remote areas with less access to medical care.”

Big pharma is also interested in the potential of e-health products in China: AstraZeneca has invested in a research base in the city of Wuxi and is investigating how Internet of Things technology could be used in conjunction with its medicines to improve patient care.

https://pharmaphorum.com/news/telehealth-firm-secures-more-cash-to-expand-in-china-japan-and-us/

Cerus Prelim Fourth Quarter and Full Year 2018 Product Revenue

Cerus Corporation (Nasdaq:CERS) announced unaudited preliminary product revenue for the fourth quarter and full year 2018 and provided 2019 product revenue guidance (see also Cerus Corporation).

Cerus’ unaudited preliminary product revenue for the fourth quarter of 2018 totaled $16.5 million compared to $16.2 million during the same period the prior year. Based on the fourth quarter unaudited preliminary product revenue, the Company expects full year 2018 product revenue to be $60.9 million, ahead of the top end of the range of the Company’s most recent guidance of $58 million to $60 million. The preliminary product revenue results have not been audited and are subject to change.

Preliminary fourth quarter product revenue would represent the highest quarterly product revenue ever reported by the Company. Cerus expects 2019 product revenue to be in the range of $70 million to $73 million, representing 15% to 20% growth compared to the preliminary 2018 results.

“The revenue growth we generated in 2018 underscores the increasing demand for safer blood components. We finished 2018 strong with quarter-over-quarter and year-to-date growth in disposable kits led by French national conversion and U.S. demand,” said William ‘Obi’ Greenman, Cerus’ president and chief executive officer.

“Over the past few months, U.S. customer orders for INTERCEPT platelets have been increasing. With the recent FDA publication of the draft guidance document on bacterial risk control strategies for platelet collection and transfusion, we could potentially experience further acceleration in customer demand in the U.S.,” continued Greenman.

Heading into 2019, the Company will continue to advance its mission to make INTERCEPT the standard of care for transfused blood components globally and to enable its customers to deliver safe and effective blood products to patients. In addition to delivering on the stated revenue growth goals, other anticipated 2019 milestones include the planned U.S. regulatory submission on pathogen-reduced cryoprecipitate, additional cryoprecipitate manufacturing partnerships, and progress on the U.S.INTERCEPT red blood cell clinical studies.

Cerus will provide complete fourth quarter and full year 2018 financial results and host a call to discuss both 2018 results and 2019 expectations in late February. ABOUT CERUS Cerus Corporation is a biomedical products company focused in the field of blood transfusion safety. The INTERCEPT Blood System is designed to reduce the risk of transfusion-transmitted infections by inactivating a broad range of pathogens such as viruses, bacteria and parasites that may be present in donated blood. The nucleic acid targeting mechanism of action of the INTERCEPT treatment is designed to inactivate established transfusion threats, such as hepatitis B and C, HIV, West Nile virus and bacteria, as well as emerging pathogens such as chikungunya, malaria and dengue. Cerus currently markets and sells the INTERCEPT Blood System for both platelets and plasma in the United States, Europe, the Commonwealth of Independent States, the Middle East and selected countries in other regions around the world. The INTERCEPT Red Blood Cell system is in clinical development.

https://www.marketscreener.com/CERUS-CORPORATION-8745/news/Cerus-Announces-Preliminary-Fourth-Quarter-and-Full-Year-2018-Product-Revenue-27883084/

Zymeworks Hits Second Milestone in Lilly Collaboration

• Lilly’s second immune-oncology candidate using Zymeworks’ novel Azymetric™ platform to start clinical trials
• Zymeworks to receive milestone payment of US$8.0 million for this second IND submission
• Lilly is one of eight pharma partners; INDs by others anticipated
• Total value of remaining potential milestones for all Zymeworks’ partnerships exceeds US$7.6 billion

Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, today reported the achievement of a new development milestone in its collaboration with Eli Lilly and Company (“Lilly”). In accordance with Zymeworks’ 2014 licensing and collaboration agreement with Lilly, Zymeworks will receive a milestone payment of US$8.0 million for Lilly’s submission of an IND application for an immuno-oncology bispecific antibody enabled by Zymeworks’ proprietary Azymetric™ platform.

“We believe that Lilly’s submission of a second IND on an Azymetric™ bispecific drug candidate within a six-month period is further evidence that Zymeworks’ platform technologies are enabling our global pharmaceutical partners to accelerate drug development into the clinic,” said Ali Tehrani, Ph.D., President and Chief Executive Officer of Zymeworks. “As one of our first collaborators, Lilly’s successes demonstrate the ease of use, productivity and promise of our proprietary platforms, especially for advancing therapeutic programs into the clinical setting.”

Under its two licensing and collaboration agreements with Lilly, Zymeworks has granted Lilly worldwide licenses to research, develop, and commercialize multiple bispecific therapeutics directed towards Lilly’s targets. To date, Zymeworks has received multiple equity investments, an upfront licensing payment and multiple research and development milestone payments under these agreements. Zymeworks is also eligible to receive further development and commercial milestone payments and tiered royalties on global product sales.

https://www.marketscreener.com/ZYMEWORKS-INC-34658200/news/Zymeworks-Reports-Second-Investigational-New-Drug-IND-Submission-Milestone-Achieved-in-Lilly-Col-27882873/

Sage Med Meets Endpoints in Phase 3 Trial in Postpartum Depression

Sage Therapeutics(NASDAQ:SAGE), a biopharmaceutical company developing novel medicines to treat life-altering central nervous system (CNS) disorders, reported top-line results from the Phase 3 ROBIN Study. This study evaluated the effect of SAGE-217 30 mg on depressive symptoms in women with postpartum depression (PPD). After two weeks of outpatient treatment, patients treated with SAGE-217 had a statistically significant improvement of 17.8 points in the Hamilton Rating Scale for Depression (HAMD-17) score, compared to 13.6 for placebo (primary endpoint, p=0.0029), with statistically significant reductions in HAMD-17 compared to placebo maintained through the end of the four-week follow-up. Remission was achieved in 45% of patients treated with SAGE-217 for two weeks as measured by the HAMD-17 compared with 23% of patients receiving placebo (p=0.0122). Results from secondary endpoints were statistically significant and consistent with the primary endpoint (see also Sage Therapeutics).

SAGE-217 was generally well-tolerated with a safety profile consistent with that seen in earlier SAGE-217 trials. Overall reports of AEs were similar between SAGE-217 (58%) and placebo (51%). Two subjects experienced serious adverse events (SAEs), one subject in each group.

“These are strong and consistent data demonstrating a rapid, stable, and clinically meaningful improvement in PPD depressive symptoms in the SAGE-217 treatment group compared to placebo,” said Jeff Jonas, M.D., chief executive officer of Sage. “This is our fifth consecutive positive study in mood disorders with our investigational medicines that utilize our innovative approach to GABA receptor modulation. Data from the ROBIN Study, along with earlier data from our studies with ZULRESSO in PPD and SAGE-217 in major depressive disorder, all point to the promise that our approach may hold – not only in changing the way PPD and MDD are treated, but also in potentially improving the lives of patients suffering from these mood disorders. The team at Sage has shown what rethinking CNS really means.”

The ROBIN Study is part of a pivotal program studying SAGE-217 as a short-course oral treatment for PPD and major depressive disorder. Summary of Top-line SAGE-217 Phase 3 PPD Trial Results Sage’s Phase 3 ROBIN Study evaluated the efficacy, safety and pharmacokinetics of SAGE-217 in 151 adult female patients diagnosed with severe PPD (HAMD-17 =26). Effect on Postpartum Depressive Symptoms: Statistically significant differences in the reduction in HAMD-17 total score of SAGE-217 versus placebo were first observed on Day 3 (-12.5 vs. -9.8; p=0.0255) and the effect was maintained at each timepoint through two weeks of treatment (-17.8 vs. -13.6; p=0.0029), the primary endpoint of the study. The effect was maintained through the four-week follow-up (-19.2 vs. -15.1; p=0.0027).

After two weeks of treatment with SAGE-217, 45% of patients achieved remission (HAMD-17 =7) compared with 23% of patients who received placebo (p=0.0122); at the end of the four-week follow-up, 53% of patients receiving SAGE-217 achieved remission compared with 30% of patients who received placebo (p=0.0102).

https://www.marketscreener.com/SAGE-THERAPEUTICS-INC-16917559/news/Sage-Therapeutics-Announces-SAGE-217-Meets-Primary-and-Secondary-Endpoints-in-Phase-3-Clinical-Tri-27883016/