Category Archives: Immunology

Launch of first breast cancer biosimilar in the UK

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MSD has announced the launch of Ontruzant®, (trastuzumab), a biosimilar referencing Herceptin® (trastuzumab/TRZ), for the treatment of early breast cancer, metastatic breast cancer and metastatic gastric cancer.

This was the first trastuzumab biosimilar to receive regulatory approval in Europe and is the first to launch in the UK.

Biosimilar trastuzumab represents the first product approved in the UK under a global biosimilars development and commercialisation agreement between MSD and Samsung Bioepis Co Ltd.

The European Medicines Agency (EMA) requires biosimilars to show they are highly similar to the reference medicine in terms of structure, biological activity and efficacy, safety and immunogenicity profile. Ontruzant (trastuzumab biosimilar (SB3)) is a monoclonal antibody and has been shown to have similar safety and efficacy as its reference product Herceptin (TRZ) in early breast cancer, with breast pathologic complete response rates (bpCR) being 51.7% and 42.0% with SB3 and TRZ respectively. The adjusted ratio of bpCR was 1.259 (95%CI, 1.085 to 1.460), which was within the predefined equivalence margins. The adjusted difference was 10.70% (95% CI, 4.13% to 17.26%), with the lower limit contained within and the upper limit outside the equivalence margin. The overall response rates were 96.3% and 91.2% with SB3 and TRZ.

Dr Mark Verrill, Head of the Department of Medical Oncology at the Newcastle upon Tyne Hospitals NHS Foundation Trust, and the deputy lead clinician for breast cancer in the North of England Cancer Network said, “This is good news for so many cancer patients and the NHS. The launch of biosimilar trastuzumab provides a high-quality treatment alternative for patients, while offering significant potential savings for the NHS. The biggest category of medicines in oncology is monoclonal antibodies and the introduction of biosimilars such as trastuzumab could provide a substantial cost saving.”

Denise Blake, Senior Lead Clinical Pharmacist at Newcastle Hospitals, explains, “The introduction of biosimilar trastuzumab provides an opportunity for the NHS to realise substantial financial savings without compromising patient care. Close collaboration between oncologists, pharmacists and nursing staff is required to ensure a seamless introduction into routine clinical practice.”

“As a company committed to inventing new treatment options for both common and neglected types of cancer, MSD is also pleased to be offering the NHS a biosimilar medicine in an established area of care. Biosimilar trastuzumab marks a significant milestone for both MSD and the oncology community, providing the UK’s first biosimilar trastuzumab, based on our collaboration with Samsung Bioepis,”explains Louise Houson, UK Managing Director, MSD.

Regulatory approval was based on a Phase III study that compared SB3 with reference TRZ in patients with human epidermal growth factor receptor HER-2 positive early breast cancer in the neoadjuvant setting.

The study showed the total pathologic complete response rates were 45.8% and 35.8% and the overall response rates were 96.3% and 91.2% with SB3 and TRZ, respectively. Eight hundred patients were included in the per-protocol set (SB3, n = 402; TRZ, n = 398). The bpCR rates were 51.7% and 42.0% with SB3 and TRZ, respectively. The adjusted ratio of bpCR was 1.259 (95%CI, 1.085 to 1.460), which was within the predefined equivalence margins. The adjusted difference was 10.70% (95% CI, 4.13% to 17.26%), with the lower limit contained within pre-specified equivalence margins and the upper limit of the confidence interval slightly exceeding the pre-specified equivalence margins (-13%, 13%).

Overall, 96.6% and 95.2% of patients experienced one or more adverse event, 10.5% and 10.7% had a serious adverse event, and 0.7% and 0.0% had antidrug antibodies (up to cycle 9) with SB3 and TRZ, respectively.

SOURCE: www.hospitalhealthcare.com

Slow-release injectable gel boosts toxicity of cancer-fighting immunotherapy drugs

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An immunotherapy drug embedded in a slow-release hydrogel invented at Rice University in collaboration with the University of Texas Health Science Center at Houston (UTHealth) appears to be highly effective at killing cancer cells.

STINGel combines a new class of immunotherapy drugs called stimulator of interferon gene (STING) agonists with an injectable hydrogel that releases the drug in a steady dose to activate the immune system to kill cancer cells. It was developed by the Rice lab of chemist and bioengineer Jeffrey Hartgerink and Rice alum Simon Young, an assistant professor of oral and maxillofacial surgery at UTHealth.

In clinical trials, immunotherapy drugs have demonstrated strong cancer-fighting abilities. Research has also found that the drugs are flushed quickly from the body, and current trials require multiple injections.

The new research, which is detailed in Biomaterials, showed that slow-release peptide gels could continuously deliver immunotherapy drugs to tumor sites for long periods of time.

Hartgerink is a pioneer in the development of self-assembling multidomain peptide (MDP) hydrogels, which mimic the body’s extracellular matrix to encourage the growth of cells and vascular systems for tissue repair. The hydrogel is injected as a liquid, turns semisolid inside the body and slowly degrades over time.

The hydrogel in the new study is also welcoming to cells, but when the invaders are cancer cells, they’re in for trouble. Immunotherapy drugs known as cyclic dinucleotides (CDNs) await them inside the gel.

Hartgerink, a professor of chemistry and bioengineering, said the concentration of CDN in the hydrogel is important.

“The normal approach to CDN delivery is simple injection, but this leads to very rapid diffusion of the drug throughout the body and reduces its concentration at the site of the tumor to very low levels,” he said. “Using the same amount of CDN, the STINGel approach allows the concentration of CDN near the tumor to remain much higher for long periods of time.”

STINGel was studied both in lab cultures and in vivo. For the in vivo portion, six groups of 10 rodents each were treated with CDN alone, control collagens alone or with CDN, MDP alone or STINGel (CDN plus MDP). Only one in 10 CDN or collagen plus CDN animals survived 105 days, but six of 10 animals treated with STINGel survived. These also proved resistant to further implantation of cancer cells, meaning their immune systems were trained to successfully identify and destroy both the existing cancer and future occurrence of that cancer, Hartgerink said.

The lab tested more common hydrogels but found that they were unable to provide the same controlled release and also failed to provide an additional benefit over CDN treatment seen in clinical trials. “The MDP hydrogel provides a unique environment for the release of CDN that other gels just can’t match,” Hartgerink said.

“The CDN we used in this study is currently in clinical trials,” he said. “We think that our STINGel approach has the potential to significantly broaden the scope of this powerful immunotherapy drug to a larger range of resistant cancers.”

SOURCE: www.news-medical.net/news/20180307

Gilead takes ‘HIV eradication’ combo into clinic

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Gilead has become a victim of its own success in hepatitis C, as it has pioneered a series of blockbuster combination drugs that are eradicating the disease, but are depleting the revenue-creating pool of infected patients.

Faced with pressure from competitors such as Merck & Co in hepatitis C, the company is now turning back to its old stomping ground – HIV, for which it has developed an arsenal of drugs that can stay the disease’s progression into full-blown AIDS.

Unlike hepatitis C, HIV is currently incurable, as drugs from Gilead and competitors like GlaxoSmithKline and Pfizer can only suppress it so that infected people can live much longer lives than in the past.

HIV creates a latent reserve within a patient’s body, lying dormant within infected CD4 cells, which can become activated and lead to the disease progressing into AIDS.

Only by tackling this reserve of infected, but dormant, T-cells can the disease be cured – and scientists have been trying for years to find ways to do this.

Gilead thinks it may have found a solution to the complex problem of tackling the infected dormant T-cells so that patients can control the disease without need for drugs.

Data from a trial in rhesus monkeys infected with simian-human immunodeficiency virus (SHIV) show that an oral toll-like receptor 7 (TLR7) agonist antiviral drug, and a broadly neutralising antibody (bNAb) could be an effective HIV eradication strategy for tackling this latent reserve.

Data from a subset of SHIV infected monkeys on suppressive antiretroviral therapy (ART) demonstrated a combination of a TLR7 called GS-9620, and a bNAb called PGT121, resulted in viral suppression after ART therapy stopped.

In the proof-of-concept study, 45% – five out out of 11 – of animals receiving both GS-9620 and PGT121 did not demonstrate viral rebound for at least 168 days after stopping ART. The other six animals rebounded but then began re-suppressing the virus without ART.

The data published at the Conference on Retroviruses and Opportunistic Infections showed that in a placebo arm 11 out 11 animals rebounded, nine out of 11 treated with only PGT121 rebounded and 10 out of 11 treated with GS-9620 rebounded.

Gilead is calling the combination therapy an “HIV eradication strategy” and will test it in phase 1 trials, in people who are HIV suppressed on approved ART therapies.

Gilead’s chief scientific officer, Norbert Bischofberger, said: “GS-9620 is currently in a phase 1b dose-escalation study in ART-suppressed people living with HIV and we have advanced GS-9722, a derivative of PGT121, into phase 1 testing.”

Gilead licensed in PGT121 from Theraclone Sciences under an agreement signed in 2014, although details of the deal were not disclosed at the time.

It was part of a portfolio of broadly neutralising antibodies discovered in collaboration with the International AIDS Vaccine Initiative and The Scripps Research Institute, Florida.

SOURCE: www.pharmaphorum.com/news

How can pharma navigate the complex marketing landscape?

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The first chapter of pharma’s commercial evolution takes us from the insatiable sales-drive of the 1980s to the present, highly complex marketing landscape.

It is easy to forget that our competitive industry still has 80-90% gross margins and, as a consequence, its traditional commercial model is driven by sales growth, rather than worrying about costs.

Under most circumstances, incremental sales drive incremental profit. Within the affiliates this is obvious, and country managers have often resisted attempts by corporate counterparts to take a centralised approach to sales and marketing, claiming their country’s commercial ecosystem is unique and not amenable to meddling.

Of course, the modern pharma company will also have to conduct market access, medical education and phase IV studies within its affiliates, but the reality is that most affiliate activity is focused on sales. For large pharma companies the sales and marketing budget usually beats R&D budgets by 1.7 times, and this is becoming increasingly difficult to justify.

Rise of primary care dominance

Throughout the 1980s and 90s the focus on sales-driven growth led to the evolution of some very different ways of working within primary care, from co-promotion and co-marketing with embedded local players, to the ‘petal’ system of multiple salesforces detailing overlapping product ranges.

The purpose of these techniques, together with employment of contract sales teams, was a sort of ‘shock and awe’ strategy which swamped the physician with frequent visits about particular products. The competitive response was usually swift and commensurate, resulting in a commercial arms race between players within a hotly contested therapeutic area.

This was known as the ‘share of voice’ model, and when applied to large primary care categories, it drove top line growth so successfully that governments and institutional payers were forced to find a response to escalating drug bills around the world.

Backlash from health technology

This response varied from country to country, but has taken two main forms; the Health Technology Assessment response and the consolidated payer response. Throughout the 1990s and 2000s, in the UK (NICE), much of Europe, Australia and parts of Asia, there has been systematic developing of a process that assesses whether a product represents value for society.

Much of the health economics work is shared among countries, and pricing comparisons made between the same product in different countries are routine. The benchmarks for the monetary value of a healthy human being are the subject of debate, but are necessary to make budgetary choices in a system without unlimited resources.

The consolidated payer model, operating in the US through pharmacy benefit managers such as Express Scripts, relies on large payers exerting pressure on manufacturers for rebates, with some undifferentiated product portfolios having to rebate as much as 50% of their gross price.

The impact of health technology assessments can be seen today, manifesting itself in pricing pressure, therapeutic substitution, a diminution of decision-making by physicians and a conscious shift towards products with a confirmed medical need. A decline in R&D productivity, however, has not made this process easy.

Dead end: Primary care hits a wall

Many commentators blame the decline in R&D productivity for the steep fall in product approvals through the 2000s but, in reality, there have been several forces at work.

The rise in genomics, together with high-speed screening techniques, led to a belief that chemical libraries could be screened against unprecedented targets and that optimised drug candidates would flood through the discovery phase into phase I trials.

The sharp product rise in the early clinical phases then came to a shuddering halt during phase II ‘proof of concept’ studies, when large numbers of clinical failures unveiled the reality – there is no short cut to understanding disease biology.

As research cul de sacs were explored, a squeeze on primary care products began in the form of price pressure from above and greater safety demands from below. As a consequence, and aided by the rise in technology, a rapid increase in the proportion of newly-approved, biological in origin drugs commenced.

Monoclonal antibodies, vaccines, enzyme replacement therapy and other therapeutic peptides, aided by insatiable demand for insulin, developed strong sales and completely changed the nature of commercial interfacing with physicians.

Biologicals change the commercial dynamic

The pressure on primary care products, together with the impact of the patent cliff in 2012/13, have combined to drive sales of primary care products into stagnation. Much of industry downsizing, particularly within commercial operations, has been in response to this.

Perhaps most merger and acquisition activity within pharma also has its origins in this relentless pressure on primary care sales and the need to reload the pipeline quickly with biologicals and specialties.

The success of biologicals and other specialties, such as oral cancer drugs, in terms of both approval and sales, has required the industry to change its commercial emphasis. The huge traditional focus on primary care or family doctors has changed to specialists, and their support workers within a secondary care or hospital environment.

The increased complexity of the specialty sell, sometimes involving multiple decision-makers, formulary approval, health economic arguments, companion diagnostics and performance-related reimbursement, has required a much smaller, but more skilled group of people to interface with the healthcare network.

Many companies have yet to find the necessary mix of skills within their workforce and are still working under the old assumptions that spending on promotional activities can remain as high as it used to be under traditional models. They do so at their peril. Check out Part 2in the next issue, as promotional resources and modern data come under intense scrutiny.

SOURCE: www.pharmafield.co.uk/features

Big pharma could turn to viruses to boost cancer immunotherapies

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Merck & Co’s $394 million acquisition of Viralytics has stoked interest in oncolytic viruses, a class of drugs that have been in the shadow of the checkpoint inhibitors and CAR-T therapies that are helping to set the standard of care in cancer.

But Merck’s deal to acquire Viralytics suggests this could be about to change, according to one of the Australian company’s close competitors, Norway’s Targovax.

Representatives of Targovax interviewed by pharmaphorum said the marketplace is set to get increasingly crowded in the future as pharma tries to use the approach to improve efficacy of checkpoint inhibitors.

There is only one FDA-approved oncolytic virus, Amgen’s Imlygic (talimogene laherparepvec) in 2015, but sales have been disappointing.

But with another 10 oncolytic viruses in clinical development, and another 40 in labs, the hope is that oncolytic viruses could be used to ‘prime’ tumours before treatment with checkpoint inhibitor immunotherapy, which has a response rate as low as 20% in some cancers.

Oncolytic viruses work by injecting genetic material into cancer cells, which modify them and make them visible to the immune system, which moves in to destroy the.

The issue with Imlygic is that it is approved as a monotherapy – and the thinking is that oncolytic viruses are likely to be more effective when used in combination with other drugs, notably immunotherapy drugs such as checkpoint inhibitors.

This is the approach taken by Viralytics, and by Targovax, which is looking to find partners as it progresses its two oncolytic viruses through the clinical trial process.

Now that Viralytics is effectively part of Merck & Co, this leaves Targovax as one of the most advanced independent biotechs working with oncolytic viruses.

Bristol-Myers Squibb has also done a big oncolytic virus deal, acquiring rights late last year to an “armed virus” targeting cancer from the UK biotech, PsiOxus Therapeutics, worth almost $900 million if the project is successful.

Merck deal ‘no suprise’

Targovax’s chief medical officer, Magnus Jaderberg, told pharmaphorum in an interview that the Viralytics deal came as no surprise following strong phase 2 results from its Cavatak, based on the Coxsackievirus, back in 2015.

Jaderberg said: “As soon as they released the data we felt that somebody would go after them and we were right. We were not surprised about the deal and we think it is very positive for us.”

He expects more interest in oncolytic viruses from Roche and Genentech, which so far have not done a big oncolytic virus deal, perhaps to boost their immunotherapy Tecentriq, which has produced some mixed results in trials.

Already partnered with Medimmune on one deal, Targovax is planning a phase 2 trial of its adenovirus-based drug TG01, targeting resected pancreatic cancer in combination with Merck’s Keytruda (pembrolizumab).

This could be extended to a phase 3 trial leading to registration in this disease, where there has been no significant progress for the best part of two decades CHECK.

Targeting RAS mutations, the drug could be used in 30% of all cancers that express this biomarker, suggesting a sales potential well in excess of the $400 million a year the company forecasts if approved in early pancreatic cancer.

Also in the Targovax pipeline is ONCOS-102, an oncolytic virus, which is in phase 1b/2 trials for mesothelioma and could produce an early readout in the coming weeks.

It is also developing ONCOS-102 in partnership with AstraZeneca’s MedImmune unit and the Cancer Research Institute for ovarian and colorectal cancer.

Jaderberg has been busy tapping up his contacts in big pharma having previously worked as chief medical officer for Bristol Myers Squibb in Europe.

He has already been in talks with manufacturers of checkpoint inhibitors to try and get licensing deals in place to fund further development.

Wiklund said: “It is tough as a small biotech to lift a phase 3 programme – it is obvious we are interested in licensing out one or both of our programmes.”

But Targovax’s CFO Erik Digman Wiklund was cagey about the prospects of a big buyout as seen in the case of Viralytics. “It is incredibly unpredictable, it is difficult to make any comment,” he said.

SOURCE: www.pharmaphorum.com/news

Autoimmune disease research community gets boost from AMP RA/SLE study results

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Data from the Phase I study of collaborative industry partnership AMP are now available, meaning scientists can benefit from access to important research about Rheumatoid Arthritis and Systemic Lupus Erythematosus.

Datasets characterising individual cells in rheumatoid arthritis and systemic lupus erythematosus disease tissue from the Accelerating Medicines Partnership for Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Phase I study are now available to the research community. Scientists from across the biomedical research community can access the AMP RA/SLE datasets to explore important research questions about these autoimmune conditions.

Commenting on what they hope to achieve from the research programme, National Institutes of Health Director Francis S. Collins, M.D, Ph.D said:

“This pioneering programme seeks to speed the development of new ways to combat a range of devastating diseases that affect millions of people.”

“AMP RA/SLE is entering an exciting phase as experts around the world will begin to mine this invaluable biomedical resource in search of tomorrow’s cures.”

This study used state-of-the-art technologies to analyse individual cells from the lining of the joints in people with rheumatoid arthritis (RA) and the kidneys from people with lupus from research cohorts whose clinical characteristics were well-studied. Other research tools tend to examine signals from across populations of cells, and as such may miss important factors coming from only a few individual cells. By focusing on single cells, researchers can tease out the contributions of specific pathways inside these cells that may play a role in disease, providing a new approach to understanding autoimmunity.

Autoimmune diseases with similar characteristics

RA and lupus are autoimmune diseases that can last a lifetime, cause significant disability, greatly reduce quality of life and are associated with increased risk of early death. These disorders share similar flaws in immune function and regulation, leading to inflammation that damages tissues. People with these conditions need more and better treatments, as some fail to respond to existing therapies.

The newly released information holds clues for potential research targets that may lead to future treatment options. Availability of the data expands the search for genes, proteins, biological pathways and other factors that influence these conditions. Researchers mining the data can seek to identify treatment targets to develop medicines for diseases of interest. The data also has potential implications for precision medicine, as AMP RA/SLE researchers identify differences in the pathways active in the tissue of different patients.

Power of collaboration

The AMP RA/SLE programme is one of three AMP projects launched in 2014 as part of an unprecedented public-private partnership to identify promising biological targets for potential therapeutics and reduce the time and cost of developing them. The NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases, alongside the National Institute of Allergy and Infectious Diseases (NIAID), manages the AMP RA/SLE programme. The Foundation for the National Institutes of Health (FNIH) manages the partnership between the NIH and the external partners, which include participating members from industry (AbbVie, Bristol-Myers Squibb, Merck & Co. Inc., Pfizer Inc., Sanofi, and Takeda Pharmaceuticals International Inc.) and non-profit partners (Arthritis Foundation, Lupus Foundation of America, Lupus Research Alliance, and Rheumatology Research Foundation). Within the context of the partnership, industry and non-profit partners are also actively involved in sharing resources and expertise.

“No single organisation has the resources to take on the challenges facing the rheumatoid arthritis and lupus communities,” said Maria C. Freire, Ph.D., president and executive director of the FNIH. “AMP brings together government, pharmaceutical and not-for-profit expertise to collaboratively move therapies forward for these autoimmune diseases.”

The AMP RA/SLE investigators are currently conducting Phase II studies that include a larger cohort of patients with RA and lupus.

The Phase I data are freely available through the NIAID-sponsored Immunology Database and Analysis Portal www.immport.org. Genomic data are also being submitted to be made available through the NIH’s database of Genotypes and Phenotypes www.ncbi.nlm.nih.gov/gap.

SOURCE: www.europeanpharmaceuticalreview.com/news/73076

Pfizer might buy BMS for $130bn – but should it?

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Pfizer could soon launch a multi-billion dollar bid for immunotherapy rivals Bristol-Myers Squibb.

But moves into new fields of innovation and digital tech – such as Roche’s buyout of Flatiron – are likely to be more popular with investors.

Pfizer, the pharma company that become the world’s biggest through a series of mega-mergers, may be about to pull the trigger again.

This time, Pfizer could be sizing up Bristol-Myers Squibb, and would have to pay $125-130 billion to persuade BMS shareholders to agree any such deal, based on the company’s current $109 bn market value.

While there is always excitable chatter online about possible buy-outs, this prediction has come from a reputable source – Citi analyst Andrew Baum, one of the most high profile pharma analysts.

Last week Baum raised his price target for Bristol-Myers Squibb to $78 from $72, and he believes the probability of a Pfizer takeover has now risen from a 50/50 to a 65% chance of a bid.

At the core of BMS’ appeal to Pfizer is the huge success of its cancer immunotherapy Opdivo, which remains the leading checkpoint inhibitor, despite stiff competition from Merck’s Keytruda and others.

Baum gave three reasons why he believed Pfizer was now more likely to make a move. First is the good news BMS received from its Checkmate-227 trial in early February. This could put it back in contention in first line lung cancer treatment, where it has lost out to Keytruda and Roche’s Tecentriq.

Secondly, BMS sealed a major deal with Nektar last week on a next generation immunotherapy NKTR-214, a move which Baum believes could materially increase Opdivo’s market share.

Finally, Baum says Pfizer’s own immuno-oncology strategy is “looking increasingly suspect,” as it is failing to keep pace with the immunotherapy frontrunners. That means that a BMS buy out might be Pfizer’s last chance to have a stake in the $50bn annual immuno-oncology market.

And of course, anyone familiar with Pfizer and its current CEO Ian Read knows that big M&A deals are a Pfizer tradition. Plans for two earlier mega-mergers in recent years had to be aborted – a $118bn bid for AstraZeneca was defeated in 2014, and a $160 billion ‘reverse merger’ with Allergan had to be scrapped in 2016 because of US tax obstacles.

Now the US has passed tax reform, Pfizer has billions more to play with, and will undoubtedly be considering its options.

However times have changed, and it’s far from clear whether investors would be impressed with a mega-merger, a strategy which has fallen out of favour.

Nooman Haque is managing director of Life Sciences and Healthcare at Silicon Valley Bank’s UK division. He says ‘horizontal mergers’ which combine two broadly similar companies are less appealing in 2018.

“Pfizer are always touted as a likely acquirer, because that has been their modus operandi. But I get the sense that investors are a little bit sceptical of horizontal mergers.

“That’s because the equity story at the moment in life sciences is all about innovation – it’s not about driving out cost efficiencies and headcount reduction. That’s not the story that investors are buying into.”

Nooman says mergers based largely on cost savings and efficiency could even be viewed as a negative, because they don’t address the innovation gap.

Roche and Flatiron – the shape of things to come

Much more exciting are the companies opening up new fields such as cell and gene therapy, and digital health.
The most eyecatching deal in this latter category was Roche’s $1.9 billion outlay on Flatiron just last week.

Flatiron is a pioneer in digital health record analytics, particularly focused around cancer. By compiling and analysing real world health data digitally, Flatiron could help create a personalised medicine model which would revolutionise medicine.

Building robust digital records also opens up the possibility of AI and genomics being adopted faster into every day healthcare – something that big pharma will not want to be excluded from.

Daniel O’Day, head of Roche’s pharma division said the deal was an important step in its personalised healthcare strategy.

“We believe that regulatory-grade real-world evidence is a key ingredient to accelerate the development of, and access to, new cancer treatments. As a leading technology company in oncology, Flatiron Health is best positioned to provide the technology and data analytics infrastructure needed not only for Roche, but for oncology research and development efforts across the entire industry.”

One key point that O’Day stressed was that Flatiron’s autonomy would be preserved, as would its ability to providing its services to all, not just Roche.

While this raises questions about just how Roche will leverage its advantage, there is no doubt that this ‘open innovation’ model is the norm, and the only way to achieve penetration into a burgeoning digital health field.

Nooman comments: “It’s the sort of deal that could set off an M&A spree as Roche’s rivals look to make similar acquisitions. Novartis’s new CEO Vas Narasimhan is talking a lot about technology and AI in drug discovery, and there may be pressure on all these big players to find the ‘right’ digital deal that has the potential to transform their business.”

He adds: “Whether it’s AI drug discovery or acquiring large datasets, I don’t know, but in other industries similar follower behaviours are observed.”

Nevertheless, he agrees that finding synergies won’t be easy for Roche.

“Flatiron has a good, turbocharged Electronic Medical Record (EMR), and relationships with oncology clinics and (presumably) a great dataset. How that will be used depends on how open Roche are to change.

“The conservative vision would be to leverage those oncology clinic relationships to, for example, make recruitment and trial management easier – that’s not insignificant, but it’s also not ground-breaking.”

He says a more adventurous approach would be to deliver what Flatiron was created to do: a “data+ insights+relationships” combination which would allow Roche to develop therapies and treatment pathways that result in better patient outcomes.

“Delivering that will be a challenge, because Roche is still a large pharma company – and the fact that the deal is structured with the Flatiron team in place makes it look more like a division of Roche, feeding its oncology programme, and not a meshing of cultures.

He concludes: “Perhaps in the short term that’s the right way. But my feeling is the bigger prize is the potential for Roche to become a different type of pharma company.”

Given the huge excitement around such developments, Pfizer CEO Ian Read may think twice before pulling the trigger on a mega-merger, which would take years to deliver and would almost certainly see thousands of job losses in US-based R&D.

Pfizer does have plenty of other options, and already has partnerships with some of the most exciting biotech pioneers, including three companies working in different gene-editing technologies: Sangamo, Spark and CRISPR Therapeutics – all potential buy-out options if their platform proves its clinical value.

It is also investing in numerous small scale digital projects, including its Pfizer HealthcareHub in London. Given these options, Ian Read may well decide that 2018 is the year to move away from the tried-and-tested mega merger, and aim instead for that ‘different type of pharma company’ model now emerging.

SOURCE: www.pharmaphorum.com/news

Priority review for Shire’s HAE drug

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US regulators are undertaking a speedy review of Shire’s lanadelumab (SHP643) for the prevention of angioedema attacks in patients 12 years and older with hereditary angioedema (HAE).

HAE is a rare, genetic disorder that causes debilitating, painful and sometimes life-threatening swelling in the body.

Shire’s application for lanadelumab, an investigational fully human monoclonal antibody that specifically binds and inhibits plasma kallikrein, is supported by data from four clinical trials.

Data from the pivotal Phase III HELP study showed that subcutaneous administration of 300mg lanadelumab once every two weeks resulted in an 87 percent reduction in the mean frequency of HAE attacks.

In addition, an exploratory endpoint, which will require further confirmatory studies, showed that during the steady state stage of the trial (day 70-182) a 91 percent attack reduction was achieved with eight out of 10 patients reaching an attack free state.

In this study, no treatment-related serious adverse events or deaths were reported, the most common side effecting observed being injection site pain (29.3 percent placebo vs. 42.9 percent across lanadelumab arms).

“Physicians as well as patients in the HAE community are excited to see lanadelumab moving forward for FDA review because there is now the real possibility of having a new way to prevent HAE attacks,” said Aleena Banerji, Massachusetts General Hospital, Boston, MA, and clinical trial investigator.

The US Food and Drug Administration has granted the application a priority review, signaling its belief that the drug has the potential to provide a significant treatment benefit to patients. As such, the regulator’s assessment should be completed within eight months as opposed to 12 months, meaning that a decision is due by August 26.

SOURCE: www.pharmatimes.com/news

Gilead signs $3bn-plus gene-editing deal with Sangamo

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Gilead Sciences has claimed another stake in the emerging cell therapy sector with a $3bn agreement to use Sangamo Biosciences gene-editing platform for new cell-based cancer therapies.

The company seems determined to stay in the forefront of the pharma industry’s push into cell therapies, with the latest deal coming shortly after it acquired CAR-T specialist Kite Pharma for $12bn and almost immediately bolted on another CAR-T tech through the takeover of Cell Design a few weeks later.

Sangamo is getting $150m upfront from Gilead in the deal, which will see Kite claim an exclusive license to use the biotech’s zinc finger nuclease (ZFN) technology to develop up to ten off-the-shelf (allogeneic) as well as autologous CAR-T therapies. It also stands to receive up to $3bn in milestones – $300m per product – as well as tiered royalties on sales.

Kite will be responsible for all development, manufacturing and commercialisation of products under the collaboration, and will be responsible for agreed upon expenses incurred by Sangamo.

Gene-editing techniques are used to modify the cells – either harvested from patients or taken from donor stocks – that are infused into cancer patients in order to mount an immunotherapeutic assault on cancers. The deal with Sangamo means rivals in the CAR-T category such as Novartis, Celgene/Juno and off-the-shelf specialist Cellectis won’t be able to use the ZFN technology in their own gene-editing toolboxes.

ZFN is a gene-editing approach that uses a DNA-cutting nuclease enzyme attached to zinc finger -binding proteins to recognize and edit specific sequences of DNA. Other techniques include CRISPR/Cas9 – used by Novartis and Juno – and Cellectis’ favoured TALENS.

However, according to CEO Sandy Macrae, Sangamo has made significant strides in improving the precision, efficiency and specificity of ZFN, which means the technique now “sets the standard on what therapeutic genome editing should be”.

He said that Kite’s “financial strength and clear determination” to bring new cellular therapies products forward makes it an ideal partner for ZFN in this setting.

Kite highlighted the potential of the technology for developing allogeneic CAR-Ts, which have been put forward as potentially a major advance over autologous therapies, as they should be much quicker and cheaper to deliver – an important consideration given the current debate over the escalating costs of cancer treatment.

“The emergence of gene editing as a tool to edit immune cells holds promise in the development of therapies with potentially improved safety, efficacy and efficiency,” commented Gilead’s CEO John Milligan.

SOURCE: www.pmlive.com/pharma_news

Celgene reveals strong P3 Otezla data in rare inflammatory condition

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Celgene has lifted the curtain on strong new Phase 3 data for its phosphodiesterase 4 (PDE4) inhibitor Otezla (apremilast) in the treatment of Behçet’s disease, a rare immune condition characterised by a wide range of symptoms as a result of blood vessel inflammation.

Drawn from a study of 207 patients to determine the drug’s efficacy in the treatment of oral ulcers brought on by the disease, the data was presented at the 2018 American Academy of Dermatology (AAD) Annual Meeting. It was found that Otezla demonstrated “statistically significant reductions in oral ulcers” compared to placebo after 12 weeks of treatment, according to the area under the curve (AUC), which assesses the change in number of recurrent oral ulcers over time.

Additionally, Celgene reported that “statistically significant” improvements were seen in the trial’s secondary endpoints, including oral ulcer pain, overall disease activity and quality of life.

“The positive phase III findings in Behçet’s Disease reflect the unique aspects of the profile of Otezla 30 mg across inflammatory-related diseases,” commented Terrie Curran, President, Celgene Inflammation and Immunology. “Otezla 30 mg has the potential to provide a clinically meaningful new treatment option for patients and doctors and to become the first product indicated specifically for the treatment of active Behçet’s Disease with oral ulcers.”

Symptoms of Behçet’s disease can include recurrent oral and genital ulcers, skin lesions, arthritis, vasculopathy and uveitis. The root cause of the condition is unknown.

“Reducing oral ulcers, which are painful and can negatively impact quality of life, is an important goal in the treatment of people with Behçet’s syndrome,” added Dr Gulen Hatemi, Associate Professor, Istanbul University Cerrahpassa Medical School. “These findings suggest that apremilast, which reduced oral ulcers and oral ulcer pain, and improved disease activity in this pivotal study, has the potential to be a treatment option for patients with active Behçet’s syndrome with oral ulcers, for which few treatment alternatives exist.”

SOURCE: www.pharmafile.com/news/516584