Category Archives: Haematology

FDA gives go-ahead for CRISPR-based sickle cell disease trial

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Development of a stem cell therapy for sickle cell disease from Vertex and development partner CRISPR therapeutics can go ahead, after the FDA lifted a hold on a review.

The companies had applied to begin an early stage trial of CTX001, a gene therapy derived from a patient’s own stem cells, for beta-thalassemia and sickle cell disease.

Although it’s a long way from the market, the drug could be one of the first to use the revolutionary CRISPR/Cas9 gene editing technology to correct a genetic defect causing a disease.

After an application in April for a phase 1/2 trial in the UNS for adults with sickle cell disease, the FDA had further questions that needed to be resolved.

Without revealing further details, the companies said the trial had been put on hold until they could provide the information the FDA required.

The FDA has now lifted the clinical hold and allowed development to go ahead, although the companies gave no further information about the information required by the regulator.

CRISPR and Vertex have obtained approval for clinical trial applications for several countries outside the US for beta-thalassemia and SCD.

They said they are on track to begin a phase 1/2 study in SCD by the end of 2018 and are enrolling patients transfusion dependent beta-thalassemia in a phase 1/2 trial in Europe.

CTX001 uses the CRISPR gene editing technique to make a patient’s haematopoietic stem cells produce high levels of foetal haemoglobin (HbF) in red blood cells.

HbF is a form of the oxygen carrying molecule haemoglobin naturally present at birth, which is replaced by the adult form of haemoglobin.

The elevation of HbF by CTX001 could alleviate transfusion requirements for beta-thalassemia patients and painful and debilitating sickle crises for sickle cell patients.

CRISPR and Vertex began a strategic research collaboration in 2015 to discover and develop gene editing treatments using the CRISPR/Cas9 technology to correct defects in genes known to cause or contribute to certain diseases.

Vertex has exclusive rights to license up to six new CRISPR/Cas9-based treatments that emerge from the collaboration, and CTX001 represents the first treatment to emerge from the joint research program.

For CTX001, CRISPR and Vertex will equally share all research and development costs and profits worldwide.

Novartis yesterday unveiled data showing its crizanlizumab reduced occurrence of the painful and potentially fatal vaso-occlusive crises that occur when blood cells become stacked in patients with SCD, blocking arteries and cutting the oxygen supply to vital organs.

SOURCE: www.pharmaphorum.com/news/fda

Novo Nordisk to launch connected insulin pens in early 2019

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Danish healthcare firm Novo Nordisk has unveiled plans to introduce new durable, connected insulin pens in early 2019.

The new NovoPen 6 and NovoPen Echo Plus connected insulin pens will replace the NovoPen 5 and NovoPen Echo insulin pens.

Novo Nordisk will commence the launch of new connected insulin pens in the first quarter of 2019. They are expected to be available in more than 50 countries.

The company expects to deliver connectivity for its disposable, pre-filled injection pens later in 2019.

Novo Nordisk commercial strategy and corporate affairs executive vice president said: “Our non-exclusive partnership strategy allows us to integrate with the various digital platforms that people are already using to help manage their diabetes.

“We firmly believe that this will help more people realise the full benefit of our innovative medicines and begin to ease the mental burden of diabetes treatment for those individuals.”

In parallel, the company has also entered into new partnership agreements with major diabetes technology firms such as Dexcom, Glooko and Roche to enable future integration of its connected pens with various digital health solutions.

As part of the deal with Roche, the partnership will incorporate insulin dosage information from Novo Nordisk’s connected pen technology into Roche’s open ecosystem, enabling to communicate with its digital diabetes management solutions such as mySugr.

The firm will also incorporate data from connected pen devices with its partners’ diabetes management solutions such as continuous glucose monitoring (CGM) systems and blood glucose meters (BGM).

Novo Nordisk will incorporate insulin dosing data with Dexcom CGM data in the coming years.

Roche diabetes care global head Marcel Gmuender said: “We believe in the tremendous benefits integrated digital diabetes management solutions can bring to people with diabetes, caregivers and healthcare systems as part of an open ecosystem and are excited to partner with Novo Nordisk to further drive innovation in this area.”

With marketing activities in more than 170 countries, Novo Nordisk is engaged in providing treatment solutions for obesity, haemophilia, growth disorders and other serious chronic diseases.

SOURCE: www.compelo.com/medical-devices/news

Ipsen appoints two leading R&D experts in bid to strengthen oncology arm

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French pharma firm Ipsen has announced the appointment of Dr. Yan Moore as Senior Vice President, Head of Oncology Therapeutic Area and Dr. Alexander “Sandy” McEwan, as Vice President, Head of Radiopharmaceuticals.

It is hoped that the move, which has seen the company take on two leading oncology specialists within a month of each other, will strengthen the company’s oncology arm.

Alexandre Lebeaut, Executive Vice President R&D and Chief Scientific Officer, Ipsen, commented: “I am thrilled to welcome Yan and Sandy as talented leaders who will assume pivotal roles in the next phase of our R&D transformation, and whose unique goal is to accelerate the development and deliver innovative therapeutic solutions to cancer patients.”

While Tel Aviv University graduate Dr Moore’s appointment with the Paris-headquartered company is effective immediately, Dr McEwan will join Ipsen on November 1st. Both R&D leaders will report to Dr. Alexandre Lebeaut, Executive Vice-President R&D and Chief Scientific Officer.

Dr Moore brings with him a wealth of experience from large multinationals including Bristol-Myers Squibb. Sanofi-Aventis and GlaxoSmithKline. Commenting Lebeaut said: “Yan is an outstanding biopharmaceutical executive who brings over 18 years of industry experience in oncology development across solid tumors, hematology‐oncology, gene and immune‐therapy. In his new role, Yan will lead and further strengthen our global oncology development powerhouse.”

Meanwhile McEwan, the author of more than 900 articles in peer reviewed journals and past President of the Society of Nuclear Medicine and Molecular Imaging, joins the organisation from the University of Alberta in which he held positions as Professor in the Department of Oncology and Adjunct Professor for the Department of Radiology and Diagnostic Imaging.

Lebeaut noted: “Sandy is a world-renowned expert in oncology and nuclear medicine who brings to Ipsen unique experience in this field. He will play a defining role in the acceleration of the development of Ipsen’s radiotherapeutics pipeline, providing strategic direction and managing the execution of the global clinical development of both satoreotide tetraxetan (IPN01072) and Satoreotide Trizoxetan (IPN01070) and also IPN01087 programs. Sandy will build and maintain trustworthy relationships with external oncology and nuclear medicine experts, academic networks, and professional organizations.”

SOURCE: www.pharmafile.com/appointment/518915

Shire’s von Willebrand disease therapy Veyvondi approved in EU

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The European Commission has approved Shire’s Veyvondi for treatment of the bleeding disorder von Willebrand disease (VWD).

VWD is the most common inherited bleeding disorder, affecting up to 1% of the global population, and is caused by deficiency or dysfunction in the protein known as von Willebrand factor (VWF).

The commission granted a marketing authorisation for Veyvondi (vonicog alfa, recombinant von Willebrand factor) for bleeding events and treatment or prevention of surgical bleeding in adults with VWD when desmopression treatment alone is ineffective or not indicated.

Veyvondi is the first recombinant treatment for VWD that addresses primary deficiency or dysfunction of VWF while also allowing the body to restore and maintain adequate Factor VIII plasma levels.

Approval is based on outcomes from three clinical trials of a total of 80 patients with VWD exposed to Veyvondi.

These include a phase 1 multicentre, controlled, randomised, single-blind, dose-escalation study of the safety, tolerability and pharmacokinectics  in subjects 18 to 60 years of age with severe VWD.

Also in the dossier was a phase 3 multicentre, open-label study to assess the pharmacokinetics, safety and efficacy of the Veyvondi and recombinant factor VIII and Veyvondi alone in the treatment of bleeding episodes in adult subjects with severe VWD.

There was also a phase 3, prospective, open-label, uncontrolled, non-randomised, international multicentre study to assess the haemostatic efficacy and safety of rVWF with or without recombinant factor VIII in 15 adult subjects with severe VWD undergoing major, minor, or oral elective surgical procedures.

Andreas Busch, head of R&D and chief scientific officer at Shire, said: “The approval in Europe for Veyvondi marks a key milestone in our efforts to tackle unmet medical needs for those living with von Willebrand disease.

“We are excited to take the next steps in ensuring that Veyvondi is widely available across Europe to address the individual needs of those affected by the condition and in need of factor replacement.”

SOURCE: www.pharmaphorum.com/news

AZ, Amgen’s first-in-class asthma drug gets breakthrough status

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AstraZeneca and partner Amgen have picked up a breakthrough designation from the FDA for tezepelumab, a drug that AZ claims could be a “best in disease” therapy for severe asthma.

Tezepelumab is a thymic stromal lymphopoietin (TSLP) targeting antibody that would slot into AZ’s key respiratory portfolio alongside Fasenra(benralizumab), the company’s interleukin-5 inhibitor antibody which was approved for severe asthma in Europe in January but just failed a test in chronic obstructive pulmonary disease (COPD).

The new candidate is in a phase III programme called PATHFINDER – due to report results from 2020 – and according to AZ chief executive Pascal Soriot has shown remarkable activity in mid-stage testing, reducing several key asthma biomarkers including blood eosinophils, fractional exhaled nitric oxide (FENO) and immunoglobulin levels as well as cutting asthma attacks.

Drugs like Fasenra and GlaxoSmithKline’s rival IL-5 inhibitor Nucala(mepolizumab) have emerged as an important treatment option for people with severe asthma characterised by high levels of eosinophils. However, the FDA’s BTD for tezepelumab is for patients “without an eosinophilic phenotype, who are receiving inhaled corticosteroids/long-acting beta2-agonists with or without oral corticosteroids and additional asthma controllers,” says AZ.

Because it acts further upstream in the inflammatory cascade responsible for asthma, tezepelumab could be suitable for a broader range of patients than Fasenra and Nucala, and also potentially Sanofi and Regeneron’s new candidate Dupixent (dupilumab), an IL-4 and IL-13 inhibitor that is already approved for atopic dermatitis. Dupixent was filed for asthma in the US in March and is due for an FDA verdict by 20 October, but some analysts have said they also expect Dupixent to be used mainly in patients with eosinophilic asthma.

Tezepelumab new status comes on the back of the phase IIb PATHWAY study which showed a significant reduction in the annual asthma exacerbation rate compared with placebo in a broad population of severe asthma patients irrespective of patients’ characteristics at enrolment. Around 10% of all asthma patients are thought to have severe symptoms making them eligible for antibody therapies.

“Tezepelumab is exciting because it has the potential to treat a broad population of severe asthma patients, including those ineligible for currently-approved biologic therapies,” said Sean Bohen, AZ’s chief medical officer.  The BTD “will help us bring tezepelumab to patients as quickly as possible,” he added.

Biologic drugs for asthma are predicted to make several billions of dollars in sales at peak, and there are already signs of string growth for some new products. Nucala made £245m ($317m) in the first six months of the year, with later entrant Fasenra bringing in $86m. Analysts have suggested tezepelumab could be a blockbuster in its own right.

SOURCE: www.pmlive.com/pharma_news

Gilead, Galapagos JAK inhibitor clears phase II test

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A mid-stage trial of Gilead and Galapagos’ JAK1 inhibitor filgotinib has set up a phase III programme for the drug in ankylosing spondylitis as it chases down two already-marketed dugs from Pfizer and Eli Lilly – and a late-stage rival from AbbVie.

In the TORTUGA trial, filgotinib met its clinical objective of reducing disease activity scores compared to placebo in patients with AS, a severe form of arthritis affecting the spine, with more patients achieving the target 20% improvement with the drug (76%) than in the control group (40%).

The drug is also in development for rheumatoid arthritis (RA), ulcerative colitis and Crohn’s disease with phase III trials already underway in those indications and results due in the coming weeks.

The drug was generally well-tolerated in TORTUGA but one case of deep vein thrombosis gave investors some cause for concern, putting some pressure on Gilead and Galapagos’ share price yesterday before share staged a partial recovery.

DVT is a recognised side effect with Eli Lilly’s JAK1 inhibitor Olumiant(baricitinib), which finally made it to market for rheumatoid arthritis in Europe last year but was rejected in the US at its first filing attempt over the safety issue. Gilead said that in the phase II AS trial the patient had an inherited condition that raised the risk of blood clots and the DVT was not thought to be drug-related.

First-to-market JAK inhibitor Xeljanz (tofacitinib) from Pfizer has already achieved $1bn-plus sales in RA, and with Olumiant somewhat hamstring by the safety issue on its label analysts are viewing the tussle between filgotinib and AbbVie’s upadacitinib as the next big battleground in the JAK inhibitor market.

AbbVie is a little ahead in the race to market, with phase III data in hand showing that upadacitinib is more effective than AbbVie’s $18bn-a-year injectable TNF blocker Humira (adalimumab) in RA when it comes to clinical responses gauged by doctors and patients. Like filgotinib, upadacitinib is also being tested in a string of other indications, including psoriatic arthritis, Crohn’s disease, ulcerative colitis and atopic dermatitis.

The rivalry is particularly strong as AbbVie was formerly Gilead’s partner for filgotinib, before ducking out of the collaboration and throwing its weight behind its in-house candidate.

SOURCE: http://www.pmlive.com/pharma_news

NICE U-turn on Crystiva for rare bone disease

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Reversing its initial decision to reject the drug, NICE has issued a positive recommendation for Kyowa Kirin’s rare disease drug Crystiva, the first treatment approved to target the underlying pathophysiology of X-Linked Hypophosphataemia (XLH).

The U-turn is good news for the Japan company, which negotiated on the price of the treatment behind closed doors after the NICE’s  conclusion that the drug wasn’t cost effective.

the UK’s cost-effectiveness watchdog is now set to recommend the twice-monthly injection for the treatment of XLH in children and young people with growing bones, with final guidance expected in October.

Tom Stratford, CEO, Kyowa Kirin International said: It is a major development that NICE has recommended Crysvita for routine use among children and young people with XLH in England and Wales.

“This marks a step change in treatment for XLH, emphasised through the emotional testimonies provided by patient groups and clinicians following the first evaluation consultation.”

Characterised by bowed or bent legs, a short stature, bone pain and delayed walking, XLH is first seen in infants but can also affect adults.

It is caused by low levels of phosphate in the blood, resulting in life-long physical disabilities.

Until now, treating this disease has consisted of multiple daily doses of phosphate and vitamin D to counteract the effects of FGF23, a protein that when produced excessively, reduces renal phosphates in the blood.

Crysvita targets this pathway by blocking the activity of FGF23, restoring phosphate blood levels by reducing phosphate loss via the kidneys.

Commenting on NICE’s decision, Oliver Gardiner, Board Member at XLH UK, said: “This is important news for children and young adults with XLH who will now be able to benefit from Crysvita routinely on the NHS.

“Access to a treatment that tackles the underlying mechanism and has the potential to avoid or mitigate substantial physical and emotional challenges, will truly make a difference to the lives of patients and their families.”

Crysvita was already accessible to patients under the NHS via the UK’s early access programme, which will be extended to allow time for NHS England to implement NICE’s final guidance.

SOURCE: www.pmlive.com/pharma_news

Jazz’ Vyxeos wins EU nod for certain acute myeloid leukaemias

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Dublin, Ireland-based Jazz Pharmaceuticals will be celebrating news of European approval of its leukaemia drug Vyxeos.

The European Commission is allowing use of the drug to treat adults with newly diagnosed, therapy-related acute myeloid leukaemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

Vyxeos is an advanced liposomal formulation that delivers a synergistic molar ratio of daunorubicin and cytarabine, and is “the first chemotherapy to demonstrate an overall survival advantage versus the standard of care in a Phase III study of older adult patients” with these conditions, said Daniel Swisher, Jazz’ president and chief operating officer.

The application included clinical data from five studies, including the pivotal Phase III study, data from which was published in the Journal of Clinical Oncology in July.

The study hits its primary target showing a superior improvement in overall survival compared to an alternative chemotherapy regimen, with 9.6 months versus 5.9 months, respectively.

“AML is a rare cancer in Europe and patients with therapy-related AML or AML with myelodysplasia-related changes have a particularly poor prognosis compared to people with other forms of leukaemia,” said Professor Charles Craddock CBE, academic director, Centre for Clinical Haematology at University Hospitals Birmingham NHS Foundation Trust.

“Vyxeos is a new and clinically meaningful treatment option that provides a welcome advance for patients and health care professionals across the European Union.”

SOURCE: www.pharmatimes.com/news

Ionis/Akcea’s ultra-rare disease drug rejected by FDA

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The FDA has opted to refuse approval to Akcea and Ionis’ Waylivra (volanesorsen) for the treatment of the ultra-rare hereditary condition familial chylomicronemia syndrome (FCS), despite the submission of Phase 3 data from the largest-ever study of the disease.

The US regulator alerted the manufacturers via a complete response letter (CRL), originating from its Division of Metabolism and Endocrinology Products, but the reason for the rejection was not given. Submitted data had shown that Waylivra reduced triglycerides by 94% in patients compared to placebo, which raised levels by 18%

FCS is characterised by extremely elevated triglyceride levels in the blood – levels which can’t be adequately metabolised due to a deficiency off lipoprotein lipase; it severely impacts daily life and can cause a range of damaging conditions including unpredictable and potentially fatal acute pancreatitis, chronic complications due to permanent organ damage.

“We are extremely disappointed with the FDA’s decision. FCS is an ultra-rare and debilitating disease. Our disappointment extends to the patient and physician community who currently do not have a treatment available to them,” commented Paula Soteropoulos, Chief Executive Officer of Akcea Therapeutics. “We continue to feel strongly that Waylivra demonstrates a favourable benefit/risk profile in people with FCS as was reflected in the positive outcome from our Advisory Committee hearing in May. We will continue to work with the FDA to confirm the path forward.”

Dr Brett P Monia, Chief Operating Officer of Ionis Pharmaceuticals, added: “We are fully supportive of WAYLIVRA and the many patients, physicians and researchers who are working to provide the first therapeutic option for FCS, a truly life-altering disease that deserves a treatment.”

SOURCE: www.pharmafile.com/news/518434

AbbVie trial backs chemo-free Imbruvica combo regimen

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The pairing of of AbbVie’s Imbruvica and Roche’s Gazyva has hit the mark in a chronic lymphocytic leukaemia trial – raising the prospect of a new chemotherapy-free combination regimen for previously untreated CLL patients.

The iLLUMINATE trial showed that oral BTK inhibitor Imbruvica (ibrutinib) plus anti-CD20 injection Gazyva (obinutuzumab) was more effective than Gazyva plus chemo (chlorambucil) in treatment-naïve, older patents (aged 65 or more) with either CLL or small lymphocytic leukaemia (SLL) – a different form of the same disease.

The top-line data isn’t being made available just yet, but in a statement AbbVie said the duo extended progression-free survival (PFS) compared to the active control arm, adding that it will be sharing the data with regulators, in the hope of bringing “the first chemotherapy-free CD20 combination in first-line CLL treatment” to market.

The trial ties in with AbbVie’s strategy of expanding use of Imbruvica as a first-line CLL treatment and, while Gazyva has been something of a slow burner for Roche since its launch in that setting in 2014, it has started to gain momentum with sales rising 41% to CHF 278m last year.

The combination of Gazyva and chlorambucil is now recommended as a first-line therapy for CLL by the US National Comprehensive Cancer Network, which deems it a category 1 treatment, ie one with a high level of evidence backing its use, so outperforming it is a big win for the combination.

“This chemotherapy-free combination represents a potential new treatment option for patients with CLL,” said John Gribben of Barts Cancer Institute in the UK, the lead investigator for the iLLUMINATE study.

“It’s exciting to see the blood cancer treatment paradigm continue to evolve – each advance moves us one step closer to a better standard of care for these patients,” he added.

Imbruvica is already approved for all lines of therapy in CLL, and beating out chlorambucil is not a big surprise as AbbVie’s drug comprehensively outperformed the chemotherapy as a monotherapy in the head-to-head RESONATE-2 trial.

The trial was the basis of Imbruvica’s approval in 2016 as a chemo alternative in treatment-naïve CLL, and the disease accounts for the lion’s share of the drug’s sales, which grew almost 39% to $762m in the first quarter of this year, topping estimates. AbbVie is predicting sales of $3.3bn this year, well on course for its peak sales target of $6bn-$7bn.

AbbVie’s head of R&D Michael Severino said on the company’s first-quarter results call that the strategy is to build a “body of evidence” for Imbruvica – both as a monotherapy and in combination – across different CLL segments “including young and fit patients and the watch-and-wait population”.

SOURCE: www.pmlive.com/pharma_news