Category Archives: Haematology

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

Eczema drug effective against severe asthma

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Two new studies of patients with difficult-to-control asthma show that the eczema drug dupilumab alleviates asthma symptoms and improves patients’ ability to breathe better than standard therapies.

Two new studies of patients with difficult-to-control asthma show that the eczema drug dupilumab alleviates asthma symptoms and improves patients’ ability to breathe better than standard therapies. Dupilumab, an injectable anti-inflammatory drug, was approved in 2017 by the Food and Drug Administration as a treatment for eczema, a chronic skin disease.

The more than 2,000 patients enrolled in the studies suffered from moderate to severe asthma. All used standard asthma inhalers, and some also took oral steroids to control their severe asthma symptoms.

In one study, the rate of asthma exacerbations was almost cut in half for those taking dupilumab compared with those taking a placebo. On average, patients taking a placebo had close to one exacerbation per day during the year of the study. Exacerbations are periods of sudden worsening of asthma symptoms such as wheezing, coughing, shortness of breath and tightness in the chest.

Although the drug significantly reduced asthma symptoms for all patients, dupilumab worked particularly well in patients with high numbers of a specific type of white blood cell, called eosinophils, circulating in the bloodstream. For those patients, asthma exacerbations were cut by two-thirds.

“This drug not only reduced severe symptoms of asthma, it improved the ability to breathe,” said Dr Mario Castro, the Alan A. and Edith L. Wolff Distinguished Professor of Pulmonology and Critical Care Medicine. “That’s important because these patients have a chronic disabling disease that worsens over time with the loss of lung function. So far, we do not have a drug for asthma that changes the course of the disease. Current drugs for severe asthma help reduce trips to the emergency room, for example, but they don’t improve lung function.”

The first study included about 1,900 patients of at least 12 years of age and with moderate to severe asthma requiring they use at least three different inhalers to control their symptoms. One inhaler contained a corticosteroid that reduces inflammation, another contained a long-acting bronchodilator that relaxes airway muscles, and the third was a “rescue” inhaler filled with albuterol, a short-acting bronchodilator that quickly opens up the airway in the event of a more severe asthma attack.

Patients taking these inhaled medications then were randomly assigned to receive either dupilumab or a placebo for one year. Patients receiving dupilumab — an injectable antibody — also were randomly assigned to a higher or lower dose of the drug. Neither patients nor their doctors knew whether they were receiving the drug or the placebo.

In addition to reduced symptoms, the patients receiving dupilumab showed improved lung function in a test of “forced expiratory volume.” This test measures the amount of air a person can force from the lungs during a deep exhale. Patients receiving dupilumab, regardless of dose, improved their lung function by approximately 130-200 millilitres greater than those receiving the placebo. In general, there were no significant differences between the patients receiving high and low doses of dupilumab.

Rates of emergency room (ER) visits and hospitalisations also were improved for patients receiving the drug. In the placebo group (with 638 patients), on average, 6.5 percent of the patients required an emergency room visit or hospitalisation due to asthma during the study. In the dupilumab group (with 1,264 patients), on average, 3.5 percent of patients needed emergency care or hospitalisation due to asthma.

Based on the second study, Dr Castro said another benefit of the drug could be the ability to wean severe asthma patients off of chronic oral steroids, which can cause debilitating long-term side effects, including stunted growth, diabetes, cataracts and osteoporosis. The second study included about 200 patients using the same inhaled asthma medications as patients in the larger trial, plus additional oral steroids — usually prednisone — to control their more severe symptoms. Half of the patients receiving dupilumab in this study were able to completely eliminate prednisone use. And 80 percent of dupilumab-treated patients were able to at least cut their doses in half. Patients on placebo also reduced prednisone use but to a lesser degree, likely because the protocols of participating in a clinical trial help asthma control generally.

Dr Castro said doctors would like to help patients rely less on steroids for asthma control because those with severe asthma can be forced to take these drugs for decades to enable them to breathe.

“I have patients who have had to stop working and go on disability because their asthma symptoms are so severe they can no longer function in the workplace,” Dr Castro said. “I’m excited about the potential of dupilumab because I have so many patients who have maxed out on available therapies and they still can’t breathe. It can become a very disabling disease.”

Patients receiving dupilumab did experience known side effects of the drug, including pain and swelling at the injection site and a short-term bump in the number of eosinophil cells in the blood. Five patients who received dupilumab and three patients who received placebo died during the study period. According to the investigators and descriptions of these patients’ medical histories, all suffered from multiple severe medical conditions, and none of the deaths was deemed related to the study protocol.

The studies will be published online in The New England Journal of Medicine.

SOURCE: www.europeanpharmaceuticalreview.com/news/75890

GSK’s blockbuster HIV drug linked with birth defects

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Regulators in Europe and the US have issued warnings about a link between GlaxoSmithKline’s blockbuster HIV drug Tivicay (dolutegravir) and birth defects of the brain and spine.

The European Medicines Agency’s safety committee has said it is evaluating preliminary results from a study which found four cases of birth defects such as spina bifida – a malformed spinal cord – in babies born to mothers who became pregnant while taking Tivicay (dolutegravir).

The Pharmacovigilance Risk Assessment Committee (PRAC) has issued precautionary advice while assessing the study, saying Tivicay should not be prescribed to women seeking to become pregnant.

Women who can become pregnant should use effective contraception while taking Tivicay-based medicines, the PRAC said.

In a separate announcement the FDA said it was also issuing a warning following preliminary results of an ongoing observational study in Botswana, suggesting women who took Tivicay at the time of becoming pregnant, or early in the first trimester, appear to be at higher risk for these birth defects.

The US regulator warned against stopping Tivicay-containing regiments without first switching to alternative HIV medicines, as this could cause the virus to spread to the unborn baby.

Women of childbearing age should talk to healthcare professionals about other non-Tivicay containing medicines.

Tivicay, an integrase strand transfer inhibitor (INSTI) is an important drug for GlaxoSmithKline, which produces the drug through its ViiV joint HIV venture with Pfizer and Shionogi.

Tivicay (dolutegravir) is sold on its own for use as a component of combinations involving other drugs, and generated sales of £1.4 billion,

And Triumeq, which combines dolutegravir with nucleoside reverse transcriptase inhibitors abacavir and lamivudine, brings in sales of more than £2.4 billion.

There are alternatives from the same class such as Merck & Co’s Isentress (raltegravir) and combinations, and combinations containing Gilead’s elvitegravir.

These are still preliminary findings, and the warnings have been issued purely as a precaution.

But preventing HIV spreading to unborn children is important to the medical community, and if there is stronger evidence of a link with birth defects, doctors will surely look for alternative therapies.

SOURCE: www.pharmaphorum.com/news

AZ’s potassium drug Lokelma finally approved in US

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AstraZeneca badly needs new drugs on the market as several former blockbusters have been hit by generic competition – and finally its high potassium treatment Lokelma has been approved by US regulators.

The drug, a highly selective potassium-removing agent, has been approved at the third time of asking by the FDA, which had been concerned about issues at its manufacturing plant in Texas.

European regulators approved the drug formerly known as ZS-9 in March after their concerns over the issues were resolved, and after two previous rejections the US regulator is also satisfied with the technical arrangements at the facility.

AZ gained rights to the drug after buying ZS Pharma in 2015 for $2.7 billion and is designed to treat hyperkalaemia, where high potassium levels threaten kidney and heart function.

Lokelma (sodium zirconium cyclosilicate) will compete with Vifor Pharma group member Relypsa’s rival Veltassa (patiromer), which has been on the market for a few years in the US and Europe.

The Anglo-Swedish pharma has predicted sales in excess of $1 billion annually for ZS-9, although some analysts say this is a conservative estimate.

The risk of hyperkalaemia increases significantly for patients with chronic kidney disease (CKD) and for those who take common medications for heart failure (HF), such as renin-angiotensin-aldosterone system (RAAS) inhibitors, which can increase potassium in the blood.

To help prevent the recurrence of hyperkalaemia, RAAS-inhibitor therapy is often modified or discontinued, which can compromise cardio-renal outcomes and increase the risk of death.

Sean Bohen, chief medical officer at AstraZeneca, said: “The consequences of hyperkalaemia can be very serious and it’s reassuring for treating physicians that Lokelma has demonstrated lowering of potassium levels in patients with chronic kidney disease, heart failure, diabetes and those taking RAAS inhibitors.”

AZ badly needs the new sales – sales of its Crestor (rosuvastatin), a former blockbuster were down 38% in Q1, to $338 million, and overall revenues fell 4% to just under $5.2 billion.

The company is selling off its old and unwanted drugs to prop up revenues and reduce costs – but this can only be seen as a short-term measure before new revenues come on stream.

CEO Pascal Soriot also faces a shareholder revolt, after more than 37% of shareholders voted against or abstained at the firm’s annual meeting when asked to approve a £9.4m pay package for Soriot, down from £14.3 million last year.

Soriot has set a sales target of above $40 billion by 2023, despite the struggles getting new drugs to the market.

SOURCE: www.pharmaphorum.com/news