NICE approves Bayer’s liver cancer drug

NICE has given Bayer’s advanced liver cancer therapy Stivarga (regorafenib) the go-ahead after it undertook a rapid review following earlier guidance that rejected the drug.

The medicine is for adults in England and Wales whose liver is well functioning but unable to be surgically removed and who have already taken Bayer’s life extending medicine Nexavar (sorafenib).

In March this year, the National Institute for Health and Care Excellence (NICE) found that regorafenib was less cost-effective than treatments it usually considers are an acceptable use of resources for end-of-life care.

But it reversed its decision after a new commercial arrangement made regorafenib available to the NHS at a confidential, lower price.

Regorafenib is an oral multi-kinase inhibitor that blocks multiple protein kinases involved in tumour angiogenesis. It slows down the growth and spread of cancer cells by cutting off their blood supply.

Clinical evidence demonstrated that those treated with sorafenib, and who have good performance status and less severe liver impairment, live longer with regorafenib than patients having supportive care.

There was an overall survival (OS) of 2.8 months compared to placebo – 10.6 months versus 7.8 months.

Meindert Boysen, director for the NICE Centre for Health Technology Evaluation, said: “Regorafenib is an important treatment option to extend the lives of people with previously treated advanced hepatocellular carcinoma after they’ve already been prescribed sorafenib.

“We are pleased that the company has responded by seeking a rapid review of our original guidance and offered a price that allows us to conclude that the drug is cost-effective for routine use on the NHS in England and Wales.”

This is hopeful news for patients, especially as around 15 people are diagnosed with liver cancer every day, according to the British Liver Trust.

Judi Rhys, chief executive of the British Liver Trust, said: “Hepatocellular carcinoma (HCC) is the most common form of liver cancer. It is particularly aggressive with the five-year survival rate being on average only 12% and a diagnosis is therefore devastating for the patient and their families.

“Access to the drug will potentially provide patients with valuable extra time with their loved ones.”

Earlier this month, the European Commission approved Ipsen’s Cabometyx(cabozantinib) as a second line therapy for patients who had been treated with Nexavar.

Cabometyx can be used as a second line monotherapy for hepatocellular carcinoma, giving patients another treatment option, as the only medicine previously available after Nexavar was Stivarga.

https://pharmaphorum.com/news/nice-approves-bayers-liver-cancer-drug/

New tech allows mobile-based eye tests

US ophthalmology technology firm EyeQue has launched VisionCheck, which it says is the world’s first automated optical device allowing consumers to measure and track their refractive error and order glasses with the results.

VisionCheck is based on technology developed at MIT and combines a cloud-based platform and a smartphone app with a motorised optical scope.

The company says the result is a low-cost, user friendly piece of tech that allows people to gather corrective vision measurements whenever and wherever they choose.

The scope attaches to a consumer’s smartphone screen and uses Bluetooth to send data to the phone.

VisionCheck measures refraction error of each eye and produces results in the form of EyeGlass Numbers, a standard scale showing the lens power needed to correct nearsightedness, farsightedness and astigmatism.

The smartphone attachment contains three precision optical lenses that automatically rotate internally using a high precision motor, capturing each meridian of the eye, measuring focus and astigmatism.

EyeQue has an exclusive licence for its mobile refraction measurement technology, which is based on an MIT patent employing the Inverse Shack Hartmann optical method.

Once a consumer completes a series of eye tests, results are instantly processed via EyeQue Cloud through algorithms and appear in the form of EyeGlass Numbers with spherical, cylindrical, and axis figures – the same values an ophthalmologist uses to issue a prescription.

Consumers can use these results to order eyeglasses through online retailers from the convenience of home – saving time and money both in terms of taking a test and obtaining their new glasses.

It has already been named as a CES Innovation Awards honoree in the Technology for a Better World category.

The optical scope contains a rechargeable battery, a Bluetooth control interface and a sophisticated touch mechanism.

The smartphone application is free to download and includes a uniquely accurate digital pupillary distance (PD) tool enabling the user to gather their PD, a measure required to order eyeglasses.

EyeQue hopes that a kickstarter campaign will encourage people to take pre-orders, as well as allowing it to gather product feedback, and reward early adopters of its technology.

https://pharmaphorum.com/news/new-tech-allows-mobile-based-eye-tests/

Unum presents preliminary results from Phase 1 Study ATTCK-17-01 at ASH

Unum Therapeutics announced preliminary results from the ongoing Phase 1 ATTCK-17-01 study, testing ACTR087 in combination with SEA-BCMA in patients with relapsed/refractory multiple myeloma at the American Society of Hematology meeting. First-in-human dosing of single agent SEA-BCMA, and of ACTR087 in combination with SEA-BCMA, in the ATTCK-17-01 multi-center, open-label Phase 1 dose-escalation study was well-tolerated, with no dose-limiting toxicities in the first three cohorts. Following infusion, ACTR+ T cells were detectable in these patients and demonstrated expansion post infusion. Furthermore, early disease assessments suggest combination activity of SEA-BCMA with ACTR087. These data support continued dose escalation of ACTR087 and SEA-BCMA in the trial. The majority of subjects, including at the lowest SEA-BCMA dose levels, demonstrated increasing serum and urine M protein levels during SEA-BCMA single-agent dosing that stabilized or decreased following ACTR087 administration, suggesting combination activity of ACTR087+SEA-BCMA. Subjects exhibited early increases in interferon gamma following ACTR087 administration, and additional elevations following subsequent SEA-BCMA administrations, suggestive of antibody-dependent T cell activation. SEA-BCMA was well-tolerated with no serious adverse events related to SEA-BCMA reported. No DLTs after the SEA-BCMA single-agent dosing period or after the ACTR087 + SEA-BCMA combination were reported across all three cohorts. No severe events of cytokine release syndrome or severe neurological events were reported.
https://thefly.com/landingPageNews.php?id=2830799

Autolus: Initial Data from Phase 1/2 Lymphoma Trials at ASH

Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, today highlighted updated results from its ongoing Phase 1/2 AMELIA clinical trial of AUTO3 in  patients with relapsed/refractory pediatric acute lymphoblastic leukemia (pALL) and its ongoing Phase 1/2 ALEXANDER clinical trial in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) presented at the 60^th American Society of Hematology (ASH) Annual Meeting,  San Diego, California. AUTO3 is a dual-targeted therapy incorporating two separate chimeric antigen receptors (CARs).  Observations from preclinical studies indicate that AUTO3 independently targets CD19 and CD22. AUTO3 is designed to reduce relapse driven by antigen loss, a key defense mechanism used by the tumor cells and the primary cause of relapse in pALL.

“The preliminary results of the AMELIA trial indicate that AUTO3, the first dual targeting CD19 and CD22 CAR T cell therapy under development for pediatric ALL, appears to have a manageable safety profile, with the potential to overcome target-negative relapse, a major limitation of current CD19-targeted therapies,” said Professor Persis Amrolia, lead investigator and Consultant in Bone Marrow Transplant at Great Ormond Street Hospital (GOSH) and NIHR Research Professor of Transplantation Immunology at UCL Great Ormond Street Institute of Child Health (ICH).

“In the ALEXANDER trial, preliminary results indicate that AUTO3 followed by consolidation with a limited duration of anti-PD1 therapy appears to have a manageable safety profile at the doses evaluated. This is the first therapy that aims to address two emerging resistance mechanisms for non-Hodgkin lymphoma, target-negative relapse and checkpoint upregulation,” said Dr. Anas Younes, Chief, Lymphoma Service at Memorial Sloan Kettering Cancer Center.

https://www.prnewswire.com/news-releases/autolus-therapeutics-presents-initial-auto3-clinical-data-from-phase-12-clinical-trials-in-b-cell-malignancies-at-the-60th-ash-annual-meeting-300758669.html

China AIDS group ‘really regrets’ role in gene-editing

The head of a Chinese AIDS support group expressed deep regret Friday for helping a scientist recruit participants for a controversial experiment claiming to have created the world’s first genetically-edited babies.

The medical trial, which was led by Chinese scientist He Jiankui, purports to have successfully altered the DNA of twin girls, whose father is HIV-positive, to prevent them from contracting the virus.

The founder of the Baihualin (BHL) China League, who calls himself “Bai Hua”, reportedly introduced 50 families to He’s team for clinical trials.

The AIDS support group operates various online chat groups, including some dedicated to married couples affected by the disease — the perfect source for He’s experiment.

“I admit that I really regret this incident, and am also very worried about these families and their children,” Bai wrote in statement on BHL’s blog Friday.

“I really want to say that I was tricked, but I don’t want to push away responsibility either,” Bai added.

He’s experiment has prompted widespread condemnation from the scientific community in China and abroad, as well as a harsh backlash from the Chinese government.

On Thursday, the Chinese ministry of science and technology stressed its opposition to the gene-editing baby experiment, and demanded a halt to the “scientific activities of relevant personnel”.

The Chinese scientist’s claims were “shocking and unacceptable” and breached “the bottom line of morality and ethics that the academic community adheres to”, vice minister Xu Nanping told state broadcaster CCTV, warning that it may have broken the law.

China’s National Health Commission has ordered an investigation into He’s experiment.

– China’s AIDS epidemic –

The public outcry over He’s experiment has drawn attention to the growing HIV/AIDS epidemic in China, which has seen a drastic surge in new cases in recent years.

Last week, citing remarks at a national health commission conference, official news agency Xinhua reported that there were an estimated 1.25 million HIV-positive people in China.

According to statistics from UNAIDS, an international organisation dedicated to AIDS advocacy, a total of 36.9 million people around the world were living with HIV in 2017.

In the 1990s, rural parts of China — particularly the central province of Henan — endured the country’s most debilitating AIDS epidemic.

It stemmed from a tainted government-backed blood donation programme and infected tens of thousands of people, including entire villages.

However, sexual transmission is now the primary way of contracting HIV in China, not blood transfusions. According to a Xinhua report in September, 93.1 percent of new reported cases in the second quarter were through sex.

The same report said the number of people with HIV/AIDS in China surged 14 percent year-on-year as of the end of June, or by about 100,000 people.

China also has a long history of ostracism of HIV/AIDS patients, which further complicates prevention efforts.

HIV-positive individuals have faced discrimination in the Chinese job market for years, and foreigners with the virus were banned from obtaining visas until 2010.

In December 2014, more than 200 people signed a petition to expel an HIV-positive eight-year-old boy from their village, prompting a national debate and highlighting the stigma involved.

“I hope that everyone can view the HIV/AIDS community in a correct way, and not discriminate against those with HIV/AIDS,” emphasised Bai in his statement Friday.

https://www.france24.com/en/20181130-china-aids-group-really-regrets-role-gene-editing

Kura Has Proof of Concept in Lymphoma, Validation of Therapeutic Target at ASH

-Two CRs, four PRs (46% ORR) observed in advanced AITL patients in Phase 2 trial of tipifarnib in PTCL –

– AITL and other PTCL patients with high CXCL12 expression experienced 50% ORR and 90% clinical benefit with tipifarnib after median of three prior therapies –

– High expression of CXCL12 observed in approximately 40% of PTCL and was associated with poor prognosis for standard-of-care therapy –

– Management to host webcast today at 11:30 p.m. ET / 8:30 p.m. PT –

 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, reported preliminary data in angioimmunoblastic T-cell lymphoma (AITL) and CXCL12+ peripheral T-cell lymphoma (PTCL), the two expansion cohorts in its Phase 2 clinical trial of its lead drug candidate tipifarnib in patients with relapsed or refractory PTCL.

The data, presented today at the American Society of Hematology (ASH) Annual Meeting in San Diego, showed encouraging activity with tipifarnib in late-stage PTCL patients, including a significant association between CXCL12 expression and clinical benefit, and proof of concept in AITL, an aggressive form of T-cell lymphoma often characterized by high levels of CXCL12 expression. A copy of the poster is available on the Company’s website at www.kuraoncology.com.

“The mechanism of action of farnesyl transferase inhibitors has remained elusive for several decades,” said Antonio Gualberto, M.D., Ph.D., Head of Development and Chief Medical Officer of Kura Oncology. “Our initial data in HRAS mutant head and neck cancer provided strong evidence of activity in tumors driven by this oncogene. However, many other tumors such as T- and B-cell lymphomas, myeloid leukemias, pancreatic or breast cancers, in which anecdotal evidence of tipifarnib activity has been reported, do not usually carry HRAS mutations. We believe the preliminary results reported at ASH validate our observation that the CXCL12 pathway is a therapeutic target of tipifarnib and provide a potential path to expand the development of tipifarnib well beyond HRAS mutant solid tumors by using CXCL12-related biomarkers to enrich for patients most likely to benefit from treatment. We will continue our efforts to identify these patient subsets and to bring this important drug candidate to patients in need.”

As of November 21, 2018, a total of 39 patients were enrolled in the ongoing Phase 2 trial, including 19 patients with AITL (16 patients in the AITL extension cohort and 3 patients in the previous portion of the study). Six of the 16 AITL patients were not evaluable as of the data cutoff date, including two who were pending initial efficacy assessments. Of the 13 evaluable AITL patients, two achieved a complete response (CR) and four achieved a partial response (PR), for an objective response rate (ORR) of 46% (six of 13). According to the study protocol, the AITL cohort is considered positive when four or more responses are observed.

The study also identified a particularly responsive subset within AITL and non-AITL patients. Specifically, patients with a high ratio of expression of CXCL12 to its receptor CXCR4 experienced a 50% ORR (five of 10) and a 90% clinical benefit rate (nine of 10 with either complete response, partial response or stable disease) with tipifarnib. Patients in this Phase 2 trial had a median of three prior lines of therapy (range 1-7). The high CXCL12/CXCR4 expression ratio had 90% sensitivity and 93% specificity to identify PTCL patients likely to benefit from tipifarnib.

Webcast Information

Kura’s management will host a webcast at 11:30 p.m. ET / 8:30 p.m. PT today, December 2, 2018, following the conclusion of the poster presentation at the ASH 2018 Annual Meeting. The live audio webcast and slides of the presentation will be available from the Investors and Media section of the company website at www.kuraoncology.com, and will be archived there for 30 days.

https://www.marketscreener.com/KURA-ONCOLOGY-INC-24827079/news/Kura-Oncology-Announces-Proof-of-Concept-in-Angioimmunoblastic-T-Cell-Lymphoma-Validation-of-CXCL12-27693664/

Immune Design: Longer Response, Survival in Lymphoma with Combo

• Overall Response Rate (ORR) of 46% in Patients Receiving the Combination
• TLR4 Biomarker Continued to Show Higher Response Rate for Patients with High TLR4 Expression (71% ORR)
• Long-term Follow Up Shows 11.1 Months Progression Free Survival

Immune Design (Nasdaq: IMDZ), an immunotherapy company focused on next-generation therapies in oncology, today announced long-term follow up results from a randomized Phase 2 clinical trial of 10 ug intratumoral G100, a TLR4 agonist, with or without pembrolizumab, in follicular lymphoma patients.

In the 26 naïve and relapsed/refractory patients in the randomized trial, the data continue to support the clinical activity of G100, with overall response rates of 46% and 23% in patients receiving a G100 regimen that includes low-dose radiation, with or without pembrolizumab, respectively. Also, disease control was shown in 92% and 85% of patients treated with the G100 regimen with or without pembrolizumab, respectively.  In addition, responses appeared to be durable, with overall progression free survival at 11.1 or 7.4 months in patients treated with the G100 regimen with or without pembrolizumab, respectively. The data were presented today at the American Society of Hematology Annual Meeting being held in San Diego.

“Follicular lymphoma continues to be a difficult-to-treat malignancy, particularly in the relapsed setting, and to date immunotherapy has not been successful and the current standard of care is associated with a number of serious adverse events,” said Carlos Paya, M.D., chief executive officer of Immune Design.  “We are encouraged by the potential for lymphoma patients with G100, a first in class immuno-modulatory agent that leads to systemic anti-lymphoma benefit when injected intratumorally. The high response rates, favorable durability and excellent safety profile we’re seeing for G100 has prompted us to embark on a potentially pivotal clinical trial in the relapsed refractory setting, as well as pursue additional trials in earlier lines of therapy in follicular lymphoma and other malignancies.”

https://www.marketscreener.com/IMMUNE-DESIGN-CORP-16953839/news/Immune-Design-Reports-Increased-Overall-Response-Rate-and-Longer-Progression-Free-Survival-of-Pati-27693665/