19 June 2018

China approves immune-oncology agent for previously treated NSCLC  

China National Drug Administration (CNDA) has approved Bristol-Myers Squibb’s Opdivo (nivolumab injection) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior platinum-based chemotherapy in adult patients without EGFR or ALK genomic tumour aberrations.

This is claimed to be China’s first and only programmed cell death (PD-1) inhibitor and is the only Immuno-Oncology (I-O) agent to show a superior survival benefit when compared with chemotherapy, based on data from the company’s Phase 3 CheckMate -078 trial.

Guangdong General Hospital tenured director and Chinese Thoracic Oncology Group chair Professor Yi-Long Wu said: “Lung cancer is a major public health issue in China, representing the highest incidence and mortality among all cancers in the country. With most lung cancer patients already at an advanced stage when diagnosed, prolonging survival is an important goal.

“The approval of Opdivo as the first I-O agent in China is a significant therapeutic advance and is great news for patients and clinicians alike, offering for the first time an I-O treatment option that is proven to extend survival in predominantly Chinese patients with previously treated NSCLC.”

This approval comes based on results from the Phase 3 CheckMate -078 trial of Opdivo against chemotherapy among patients with earlier treated NSCLC.

The trial was stopped last November as the independent Data Monitoring Committee concluded that Opdivo demonstrated superior overall survival compared with chemotherapy.

The application later got priority review by the Centre for Drug Evaluation in China.

Bristol-Myers Squibb executive vice president and chief commercial officer Murdo Gordon said: “With approvals in more than 60 countries, Opdivo is a global standard of care for previously treated NSCLC, and we are proud to bring this foundational I-O treatment option to patients and physicians in China. We look forward to continuing to work together with the CNDA to usher in additional healthcare innovations in China, with our shared commitment to moving quickly to help patients.”

15 June 2018

Sage and Shionogi to advance depression drug in Asia

US-based biopharmaceutical Sage Therapeutics has partnered with Japanese pharmaceutical firm Shionogi over clinical development and commercialisation of its drug candidate, SAGE-217.

The partners will advance the product for a variety of indications, including mood and movement disorders such as major depressive disorder (MDD), in Japan, Taiwan and South Korea.

SAGE-217 is a positive allosteric modulator formulated to selectively target synaptic and extrasynaptic GABAA receptors involved in the functioning of the central nervous system (CNS).

Sage Therapeutics CEO Jeff Jonas said: “By working together, we believe we can expand the global footprint for SAGE-217 alongside our ongoing efforts in the US and EU.

“As we have always said, our goal is to build a fully-integrated, multi-national biopharmaceutical company and this collaboration moves us another step closer to achieving the goal.”

Under the terms of the strategic alliance, Shionogi will pay $90m upfront to Sage, which is additionally eligible for another $485m in development and commercial milestone-based payments.

Shionogi will carry out clinical development, regulatory filings and commercialisation activities for all of SAGE-217’s indications in Japan, Taiwan and South Korea.

Meanwhile, Sage will obtain potential tiered royalties on sales of SAGE-217 in these countries. The company also received select rights from Shionogi to co-promote the drug candidate in Japan.

Sage retains exclusive rights to develop and commercialise the product outside of Japan, Taiwan and South Korea.

11 June 2018

Pfizer wins appeal against CMA fine over epilepsy drug price

US pharmaceutical giant Pfizer has won its appeal in the UK’s Competition Appeals Tribunal (CAT) against a £84.2m fine imposed by the Competition and Markets Authority (CMA) for dramatically increasing the price of its epilepsy drug, Epanutin.

Following a three year investigation, the CMA ruled in 2016 Pfizer and its distributor Flynn Pharma had abused their dominant market position by raising the price of Epanutin from £2.83 per pack of capsules to £67.50, which represents more than a 2,000% increase. Annual NHS spending on the drug increased from £2m in 2012 to £50m in 2013.

In 2012, Pfizer’s patent for Epanutin expired and it became a generic product marketed by Flynn. In the UK, generic drugs are not subject to price controls, whereas branded products are.

Philip Marsden, the CMA’s chairman of the case decision group for the investigation, said the companies had “deliberately exploited” the generic product loophole that allowed the price increase.

He continued: “Businesses are generally free to set prices as they see fit but those holding a dominant position should not abuse this situation and set prices that are excessive and unfair. There is no justification for such rises when phenytoin sodium capsules are a very old drug for which there has been no recent innovation or significant investment.”

As well as fining Pfizer, Flynn was fined £5.2m by the CMA and both were ordered to reduce the drug prices, Pfizer in 30 days and Flynn in four months.

Pfizer and Flynn both responded by appealing the decision. Pfizer claimed it had been making the product at a loss, but it couldn’t stop making it because so many relied upon it. Flynn claimed its appeal was based on the CMA’s ‘wholly flawed understanding of the UK pharmaceutical market’.

The CTA declared that that CMA had been correct that Pfizer and Flynn held a dominant position in the market for the drug. However, it concluded the CMA had not applied the correct legal tests to assess whether the price rise was excessive and had failed to consider the correct price for the product and take into account other comparable products.

Therefore, it ruled it was in the public interest for the CMA to rectify the errors found and to reconsider its case on valid grounds.

8 June 2018

Spyryx reports positive data in first cohort of HOPE-1 trial

Spyryx Biosciences has reported positive results from the first cohort of Hydration for Optimal Pulmonary Effectiveness (HOPE-1) Phase 2 clinical trial of SPX-101 to treat patients with cystic fibrosis (CF).

The exploratory, randomised, placebo-controlled, 28-day trial has so far enrolled 46 adult CF patients who are independent of CFTR mutation type. The trial aims to enrol a total of 90 patients.

The trial’s first cohort compared a high dose (120mg), a low dose (60mg) and placebo in patients with baseline percent predicted forced expiratory volume in 1 second (ppFEV1) of 40%-80%.

During the trial, SPX-101 was given by nebulisation through a new, silent, rapid and portable nebuliser, ENaC, while ppFEV1 was measured at days seven, 14 and 28.

The cohort’s primary efficacy endpoint was the absolute change from baseline in ppFEV1 after 28 days.

The new results have shown that at day 28, a dose-related benefit was witnessed with the high dose showing a placebo adjusted increase of 5.2% in ppFEV1.

It was also found that with the high dose, ppFEV1 separation from placebo was achieved by day seven and it continued through the treatment period.

In the subgroup of moderate patients with baseline pp FEV1, less than 55% of the high dose response at day 28 was observed at 8.3%. SPX-101 was also reported to be safe and well tolerated with the most common adverse events being cough and sputum production.

HOPE-1 principal investigator Isabelle Fajac said: “There is urgent need for an effective and safe treatment to promote airway clearance for all patients with CF, regardless of their genetic mutation.

“The data shows that with this novel mechanism – internalisation of ENaC – it is possible to inhibit ENaC in the airways without impacting potassium concentrations in the blood, and this has been a goal in research for the past 30 years.

“This data is also very promising in terms of respiratory benefit gained from ENaC inhibition.”

7 June 2018

Fully automated facility for drug discovery to be built in UK

The UK Government has revealed plans to build a fully automated facility at the Rosalind Franklin Institute in Oxfordshire to enable fast, effective and hands-free molecular discovery for new medicines.

Business Secretary Greg Clark has launched the new £103m institute, which will carry out a series of projects to develop new drug discovery technologies and accelerate medicine research.

One of the new projects is called Closing the Loop on Drug Discovery and it will work towards a range of technologies for driving discovery of quality lead molecules to minimise the costs associated with the discovery process.

For the project, companies, small and medium sized enterprises, universities and the Medicines Discovery Catapult will partner to conduct research and development of the new technology.

The Rosalind Franklin Institute will work with 11 collaborators, including the University of Leeds, across life sciences, physical sciences and engineering areas.

The primary goal of the new facility is to provide a rapid alternative for existing costly processes that usually require more than ten years to discover a new drug.

It will see 150 researchers leverage a variety of systems such as artificial intelligence (AI) and robotics to develop new diagnostics, drugs and treatments.

Furthermore, the facility will feature new instruments to facilitate direct observation of interactions between drug candidates and target proteins.

University of Leeds lead scientist Adam Nelson said: “This won’t be a traditional chemistry lab. It will use robotics and AI to automate the discovery process. It will allow hundreds or thousands of candidate molecules to be investigated at a time, and we aim to increase productivity by five to ten times.

“But faster processing isn’t enough. We also want to find higher-quality starting points for drug discovery to maximise the chances of success at later stages in the pipeline.

“This will enable the UK to remain globally competitive in bringing new drugs to the market that can meet the needs of patients.”

5 June 2018

Jazz Pharmaceuticals reports positive results from TONES 5 study

Jazz Pharmaceuticals has reported positive results from TONES 5 study, a Phase 3 trial of solriamfetol for the treatment of excessive sleepiness (ES) in patients with narcolepsy or obstructive sleep apnea (OSA).

Findings of the open-label trial have showed solriamfetol’s long-term maintenance of efficacy and a tolerable safety profile in the enrolled patients.

As part of the trial, 643 patients, including 226 narcolepsy and 417 OSA, were given solriamfetol and included in the safety population, and 458 completed the study.

A total of 282 patients entered the two-week, placebo-controlled, randomised withdrawal (RW) phase, and 280 completed this phase, representing the modified intent-to-treat population.

At the end of the RW phase, patients who received solriamfetol showed improvement, while those who were switched to placebo remained worsened.

The primary endpoint in the RW phase included change in Epworth Sleepiness Scale (ESS) from beginning to end of the RW, while the secondary endpoints were patient and clinician global impression of change (PGI-C and CGI-C) respectively.

The trial had a two-week titration phase followed by a maintenance phase of up to 50 weeks.

Among the other results, the TONES 5 trial demonstrated long-term maintenance of efficacy during the open-label period for up to one year by sustained reductions in mean ESS scores and improvements on the PGI-C and CGI-C scales.

Jazz Pharmaceuticals Sleep and CNS Medicine senior vice-president Jed Black said: “If approved by the US Food and Drug Administration, solriamfetol would offer patients the first new chemical entity for the treatment of excessive sleepiness in narcolepsy and OSA in the US in nearly ten years.”

OSA is a prevalent disease where ES is a major presenting complaint in many cases.

ES in OSA is related to impairments in cognitive function, safety, productivity, interpersonal relationships, and overall quality of life.

5 June 2018

Trial shows aspirin and reflux medication prevent oesophageal cancer

Results of a new trial have showed that taking an anti-acid reflux medication along with a low dose of aspirin can thwart oesophageal cancer in people with a high risk of the disease.

Funded by Cancer Research UK, AspECT is a Phase lll randomised trial that enrolled more than 2,500 men with Barrett’s oesophagus, a condition that is partly genetic and aggravated by reflux of acid into the oesophagus.

Patients with Barrett’s are at around a 50 times higher risk of oesophageal cancer, however only 2% go on to develop the disease.

Out of those who develop the cancer, only 12% have a chance to survive for ten years or more.

As part of the AspECT trial, the patients were randomly distributed in four groups to provide different doses of esomeprazole, a proton pump inhibitor (PPI), with and without low-dose aspirin.

After following the four groups of patients for an average of 8.9 years, the researchers found that those treated with the combination of high-dose esomeprazole and low-dose aspirin for at least seven years were 20% less likely to develop oesophageal cancer than if they had been untreated.

AspECT trial lead author Janusz Jankowski said: “Oesophageal cancer is hard to diagnose and hard to treat.

“So, we’re pleased that such a cheap and well-established medicine can prevent and/or delay development of cancer for these patients.

“Our hope is that this may also offer an opportunity to prevent oesophageal cancer in wider populations.”

In addition, Cancer Research UK has funded a similar trial called WASP for women and has concluded recruiting patients.

4 June 2018

some breast cancer patients do not benefit from chemotherapy

A study of more than 10,000 early stage breast cancer patients has shown combining chemotherapy treatment with hormone therapy does not improve their survival prospects for women with the most common form of the disease. The findings were presented at the annual meeting of American Society of Clinical Oncology (ASCO) in Chicago, US.

The phase III clinical trial was the largest breast cancer treatment trial to date and all the participants had the most common form of breast cancer: oestrogen receptor positive, HER2 negative breast cancer that has not spread to the lymph nodes.

It used California-based Genomic Health’s genetic test Oncotype DX, which analyses 21 genes to predict whether a patient can be spared chemotherapy and be treated successfully with hormone therapy alone. The test provides women with a breast recurrence score.

Over a median follow-up of seven and a half years, the study met its primary endpoint of indicating hormone therapy alone was not less effective than combining it with chemotherapy. The same results were seen after nine years of follow up.

The study concluded that chemotherapy may be spared in all women over the age of 50 with hormone-receptor positive, HER2 negative breast cancer and recurrence score of between zero and 25 and all women younger than 50 with the same type of cancer and a recurrence score between zero and 15.

Research lead and Albert Einstein Cancer Centre oncologist Dr Joseph Sparano said: “This will have an immediate impact on the treatment of these women. The current guidelines have made doctors use chemotherapy without a high level of evidence, but for most patients there is no benefit.”

ASCO expert Harold Burstein said: “This study will transform care immediately, and for the better. This data provides critical reassurance to doctors and patients that they can use genomic information to make better treatment decisions in women with early-stage breast cancer. Practically speaking, this means that thousands of women will be able to avoid chemotherapy, with all of its side effects, while still achieving excellent long-term outcomes.”

The trial also showed that chemotherapy did improve the survival prospects, compared with hormone therapy alone, of women aged 50 or younger with a recurrence score between 16 and 25.

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