Non-invasive prenatal diagnosis of spinal muscular atrophy by relative haplotype dosage
Sanofi, Sobi Eye Filings For Once-weekly Haemophilia A Therapy
Sanofi and Sobi's haemophilia partnership has been under competitive pressure from new therapies like Roche's antibody Hemlibra, so the two companies are hoping a new long-acting drug candidate can revitalise the franchise.
New phase 3 data on efanesoctocog alfa (also known as BIVV001) has met its objectives in a phase 3 study, providing protection from bleeding episodes in patients with haemophilia A with once-weekly dosing.
The XTEND-1 trial also showed that BIVV001 was better at reducing the annualised rate of bleeding episodes than patients' previous therapies, according to Sanofi and Sobi, which said they will now talk to regulators to chart a path forward to approval.
BIVV001 is a factor VIII replacement therapy that is being developed as a successor to Eloctate (efmoroctocog alfa), Sanofi and Sobi's current factor VIII drug that is dosed every four days but has seen its sales decline in an increasingly competitive market.
The half life of the new drug – one of the main draws for Sanofi's $11.6 billion takeover of Bioverativ in 2018 – is extended in the body by fusing it with von Willebrand factor (vWF), a protein that binds to factor VIII in the blood and makes it more stable, protecting it from degradation.
"While advances have been made in the treatment of haemophilia, unmet medical needs still exist," said Dietmar Berger, Sanofi's chief medical officer.
"We believe efanesoctocog alfa provides higher protection for longer duration with reduced treatment burden of once-weekly dosing, and we look forward to working with regulators to bring this therapy to patients as soon as possible."
When Sanofi acquired Bioverativ forecasts for BIVV001 were that it could become a $2 billion product, although the haemophilia A market has evolved in the meantime.
The launch of Hemlibra (emicizumab) in 2017, with a label expansion in 2018 to broaden its use – had a speedy impact on Eloctate, which also came from Bioverativ's stable. Sanofi recorded a $2 billion charge in 2019 that it said was largely down to pressure on its drug.
Sales of Hemlibra meanwhile have rocketed to reach more than $3 billion last year, thanks to strong efficacy data and a convenient subcutaneous dosing regimen every one, two or four weeks, depending on the patient need.
Meanwhile, Eloctate, Hemlibra and BIVV001 if approved could all find their prospects completely altered if gene therapies for haemophilia A, currently headed by BioMarin's valoctocogene roxaparvovec or val-rox, reach the market and offer a one-shot treatment for the disease.
Val-rox has already been turned down by the FDA once however, and there are ongoing concerns about its duration of action, with signs that factor VIII levels fade over time – possibly in as little as two years.
BioMarin has said it intends to refile val-rox in the US in the second quarter of this year, around the time it hopes to hear a verdict from the EU regulatory authority.
In the meantime, the big question for Sanofi and Sobi is whether the BIVV001 data is strong enough to make inroads into Hemlibra's territory, which is a big ask.
Sanofi sees its potential in patients already taking factor VIII drugs, a $5 billion market, and also maintains that its profile will be "competitive" against treatments like Hemlibra.
Meanwhile, Sanofi is also hoping to file for approval of Alnylam-partnered RNA interference therapy fitusiran for haemophilia A and B this year, which works by suppressing antithrombin (AT), a protein that inhibits blood.
Problems with blood clots in some patients in phase 3 trials have cast a shadow over fitusiran's prospects, and it is now being tested at a lower dose to try to alleviate the issue.
Pfizer Kills Hemophilia Gene Therapy Deal, Imperiling Sangamo
Dec. 30, 2024
General Assignment Reporter
Pfizer has abandoned development of a hemophilia A gene therapy it licensed from Sangamo Therapeutics, a move that could imperil Sangamo's future.
It's a sudden turnabout for Pfizer, which had indicated it would bring the experimental treatment to regulators, albeit not one that is likely to have a significant impact on the pharma giant or patients. Another gene therapy for the rare bleeding disorder was approved last year but has mustered little interest, largely because standard-of-care is already high and gene therapies aren't yet curative.
Sangamo's leadership, though, had been depending on the treatment to help save the beleaguered biotech. According to the deal Sangamo inked in 2017, Pfizer still owed the California-based biotech $220 million in milestones.
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SubscribeHaemophilia A Trial Results 'mind-blowing'
Father-of-two Jake Omer was born with haemophilia A
British doctors say they have achieved "mind-blowing" results in an attempt to rid people of haemophilia A.
Patients are born with a genetic defect that means they do not produce a protein needed to stop bleeding.
Thirteen patients given the gene therapy at Barts Health NHS Trust are now off treatment with 11 producing near-normal levels of the protein.
Jake Omer, 29 from Billericay, Essex, was on the trial and says he feels like he has a new body.
Like 2,000 other people in the UK, his body could not make clotting factor VIII.
A minor injury used to cause severe bleeding. He remembers losing two front teeth as a child and bleeding for days afterwards.
Even the impact of walking would lead to bleeding in his joints and eventually cause arthritis.
Jake has needed at least three injections of factor VIII a week for most of his life.
But in February 2016, he had a single infusion of gene therapy.
Jake Omer: 'Like a new body'
Jake told the BBC: "I feel like a new person now - I feel like a well-oiled robot.
"I feel I can do a lot more. I feel my body allows me to do more.
"I don't think I would have been able to walk 500m without my joints flaring up, whereas now I think sort of two, three, four-mile walk - I could quite easily achieve that."
The first time he knew it had worked was four months after the therapy when he dropped a gym weight and bashed his elbow.
He started to panic, but after icing the injury that evening, everything was normal the next day.
The therapy is a genetically engineered virus.
It contains the instructions for factor VIII that Jake was born without.
The virus is used like a postman to deliver the genetic instructions to the liver, which then starts producing factor VIII.
In the first trials, low doses of gene therapy had no effect.
Of the 13 patients given higher doses, all are off their haemophilia medication a year on and 11 are producing near-normal levels of factor VIII.
Prof John Pasi, who led the trials at Barts and Queen Mary University of London, said: "This is huge.
"It's ground-breaking because the option to think about normalising levels in patients with severe haemophilia is absolutely mind-blowing.
"To offer people the potential of a normal life when they've had to inject themselves with factor VIII every other day to prevent bleeding is transformational."
Larger trials are now imminent to see if the therapy can truly transform the lives of patients.
It is also uncertain how long the gene therapy will be effective.
Liz Carroll, the chief executive of The Haemophilia Society, said: "Gene therapy is a potentially game-changing treatment.
"Despite world-leading treatment standards in the UK many still suffer painful bleeds leading to chronic joint damage."
However, she warned there was a wide variation in who responded to therapy, which still needed to be explained.
Gene therapies are likely to be spectacularly expensive. However, the current cost of regular factor VIII injections is about £100,000 a patient per year for life.
Jake says the therapy should help him live a full life with his family: "It's going to allow me as my boys grow up to be more active with them, to kick footballs about, to climb trees, to hopefully run around the park with them, not be someone who has to worry."
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