Spark and Pfizer’s gene therapy wows in haemophilia B

Gene therapy company Spark Therapeutics has published data showing its one-time treatment can almost entirely eliminate bleeds in patients with haemophilia B.

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The news confirms Spark as a frontrunner in the groundbreaking field, where it is poised to gain the first ever US approval for a gene therapy within weeks.

The interim data published in the New England Journal of Medicine shows that in 10 patients given the gene therapy SPK-9001, the annualised bleeding rate was cut by 97%, from a mean rate of 11.1 events per year to 0.4 events per year.

The gene therapy also freed the 10 men from daily infusions of factor IX to help prevent bleeds, their use dropping by 99%.

The data confirms earlier signs that the drug is highly effective, the follow-up amounting to a 492-week cumulative period.

Safety data from the open label phase 1/2 trial was also encouraging , with patients recording no serious adverse events, no thrombotic events or the development of factor IX inhibitors.

Spark’s Katherine High

“People who live with haemophilia today face a lifelong need for vigilant monitoring and recurrent factor concentrate infusions to prevent spontaneous, potentially life-threatening bleeds and to protect their joints, said Katherine High, M.D., president and head of Research and Development at Spark Therapeutics and co-author of the paper.

“The discipline required to execute the usual prophylactic regimen can exact a heavy toll on quality of life, and these regimens result in significant costs to patients, families and the health care system.”

She added: “The data suggest a one-time infusion of SPK-9001 has the potential to safely sustain factor IX coagulant activity level that may result in the termination of baseline prophylaxis factor infusions, significantly reduce bleeding, and nearly eliminate the need for exogenous factor IX concentrate infusions.”

SPK-9001 was granted an FDA Breakthrough Therapy Designation 18 months ago, and now looks ready to enter pivotal trials, which will be conducted by Spark’s development partner Pfizer.

Spark’s first product Luxturna (voretigene neparvovec), a treatment for a rare blindness, is now just one step away from FDA approval. The all-clear from the regulator will make it an historic milestone, the first ever gene therapy approved in the US.

The new haemophilia data is further good news for Spark, although haemophilia B is a far smaller market than haemophilia A, where it is developing SPK-8011.

Competitors in the haemophilia A gene therapy space include BioMarin and a partnership between Sangamo and Pfizer.

These companies will all be presenting data from their gene therapies at the American Society of Hematology (ASH) meeting , which gets underway on Saturday in Atlanta.

Clovis PARP drug gets fast US review in new ovarian cancer use

The FDA has promised a fast review for expanded use of Clovis Oncology’s ovarian cancer pill Rubraca, that could bring it up to speed with a rivals from AstraZeneca and Tesaro.

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Clovis wants approval for its Rubraca (rucaparib) twice-daily pill as a maintenance therapy in women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are platinum sensitive, and in a complete or partial response to platinum-based chemotherapy.

Crucially, Clovis wants a licence in this indication regardless of a patient’s BRCA mutation status, negating the need for an expensive test and giving an opportunity for use in a wider patient group.

This will bring it into line with its rivals in the poly (ADP-ribose) polymerase (PARP) inhibitor drug class, AstraZeneca/Merck & Co’s first-to-market Lynparza (olaparib) andesaro has also got its once-daily PARP drug Zejula (niraparib).

The FDA has granted Clovis a six-month priority review, as opposed to the standard 10-month period, and has promised to make a decision by April 6 next year.

The US regulator granted the fast review because of significantly improved progression-free survival data in all ovarian cancer patient populations studied – in fact Rubraca’s PFS data has outshone both of its rivals.

Clovis’ filing is based on data from the phase 3 ARIEL3 clinical trial, a double-blind, placebo-controlled trial that enrolled 564 women with platinum-sensitive, high-grade ovarian, fallopian tube, or primary peritoneal cancer.

The primary efficacy analysis evaluated three prospectively defined molecular sub-groups in a step-down manner – BRCA mutant, HRD-positive; and, finally, the intent-to-treat population, or all patients treated in ARIEL3.

Rubraca is also under review in Europe and a decision is expected from the CHMP regulatory committee at the end of this month.

This would pave the way for an EU-wide licence early next year, and if approved Clovis will then apply for the extended use in Europe.

Clovis in October filed for a second-line or later maintenance treatment indication in the US, based on the ARIEL data.

Studies open for enrolment or under consideration include ovarian, prostate, breast, gastroesophageal, pancreatic, lung and bladder cancers. Clovis holds worldwide rights for Rubraca.

Novartis/Amgen’s migraine drug excites with phase 3 data

Novartis and Amgen’s migraine drug erenumab has got a further boost with new phase 3 data showing it halved migraine days in 50% of patients.

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The companies published top line results from STRIVE around a year ago, but they have now lifted the lid on the details of the study used as a basis for filings in the US and EU.

Erenumab will be branded as Aimovig and is from the calcitonin gene related peptide (CGRP) class of drugs, with several competitor antibodies from different companies approaching the market.

Novartis and Amgen have taken the lead, but Teva’s fremanezumab is close behind, along with Eli Lilly’s galcanezumab and Alder’s eptinezumab.

These are the first fully reported phase 3 results from a drug in the CGRP class, putting Novartis and Amgen in pole position in the race to get to market.

The FDA is due to make a regulatory decision on erenumab next May, and a decision from EU regulators is due later in 2018. Teva filed fremanezumab with the FDA last month.

Among the group, erenumab is the only fully human monoclonal antibody, designed to reduce side effects associated with the competitors, which have been humanised.

STRIVE enrolled 955 patients, who were randomised to receive either placebo or subcutaneous erenumab 70mg or 140mg once a month, for six months.

Patients taking erenumab at the higher dose experienced a significant 3.7-day reduction in monthly migraine days from the baseline of 8.3 days.

Those on the 70mg dose saw a 3.2 day reduction, while those on placebo saw a 1.8 day reduction.

Fifty percent of patients taking erenumab 140mg had their migraine days cut by at least half, representing a significantly higher likelihood of achieving this response compared to placebo.

On the lower dose, 43.3% had their migraine days cut by at least half, compared with 26.6% on placebo.

Erenumab could bring in sales of almost $500 million in 2022 if approved, although analysts say Teva’s fremanezumab could push through the billion-dollars a year mark.

If approved, Novartis will co-market erenumab in the US, while Amgen has exclusive rights in Japan. Novartis has exclusive rights to market the drug in the rest of the world.

New Teva CEO axes R&D chief Hayden in boardroom shakeup

Shares in troubled Teva Pharmeceuticals have ticked up after incoming CEO Kare Schultz pledged to tackle “internal inefficiencies”, shaking up the company and axeing three high-profile executives.

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This includes Michael Hayden, who has been the company’s head of research since 2012.

Teva is struggling to pay off debts that amount to $30 billion, built up following its acquisition of Allergan’s generics business last year.

The Israel-based firm is also facing a severe patent cliff as its big-selling multiple sclerosis drug Copaxone faces generic competition in the key US market.

Schultz was lured away from the CEO role at Lundbeck, and has announced plans to restructure the company and do away with a two-way split between its generics over-the-counter, and branded medicines operations.

There will be some high profile casualties – chief scientific officer and R&D head Michael Hayden will retire at the end of the year, along with CEO of Teva’s global medicines group, Dipankar Bhattarcharjee, and Rob Koremans, president and CEO of the global specialty medicines group.

Michael Hayden is set to leave Teva

Interim chief financial officer Mike McClellan will get the job on a permanent basis, while Hafrun Fridriksdottir becomes the executive vice president of global R&D.

New structure

Some former global units will be integrated into the new structure, while others will be made redundant.

To increase efficiency, generic and specialty R&D will combine into a single global group responsible for all R&D, including generics, new drugs, and biologics.

Teva will now operate through three regions – North America, Europe and Growth Markets.

Each of the regions will manage the entire Teva portfolio, including, generics, specialty branded drugs and OTC, fully accountable for profits and losses.

A newly created division – Marketing and Portfolio – will oversee the link between regions, R&D, and operations throughout a drug’s lifecycle, and optimise portfolios across therapeutic areas.

In a string of other new appoints, Brendan O’Grady takes on a role as vice president of North America Commercial, and Richard Daniell becomes president of European Commercial after heading up the company’s generics business in Europe.

Former head of respiratory medicines and chief operating officer, Sven Dethlefs, has also been appointed as executive president of global marketing and portfolio.

Continuing in their current positions will be Carlo do Notaristefani, EVP of global operations, Iris Beck-Codner, EVP global brand and communications, Mark Sabag EVP for global human resources and David Stark, chief legal officer.

Kare Schultz

Kare Schultz added: “I would like to thank Dr Michael Hayden, Dr Rob Koremans and Dipankar Bhattacharjee for their profound contributions to Teva over the past decade and for their tireless dedication to the many patients we serve.”

Catalyst to re-submit rare disease drug after trial success

Catalyst Pharmaceuticals is to go back to the FDA with new data from Firdapse, its treatment for ultra-rare neuromuscular disease, Lambert- Eaton myasthenic syndrome (LEMS).

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The drug was rejected last February when the FDA refused to review Firdapse, saying its clinical dossier was not sufficiently complete.

Firdapse has already been on the European market for about seven years as a treatment for LEMS, but it appears the FDA has taken a much different approach to its European counterparts when it comes to approving the drug.

In Europe amifampridine-containing medicines have been used for around 20 years, and regulators were content to approve Firdapse based on previously published studies involving around 38 patients.

But the FDA has required a whole new set of clinical trial data, although it has tried to accelerate development by granting a Breakthrough Therapy designation, and helping development by providing a Special Protocol Assessment.

This resulted in a trial with two defined co-primary endpoints – a quantitative myasthenia gravis (muscle weakness) score, and subject global impression.

Results from the LMS-003 trial announced today showed that the trial of the oral medicine met both endpoints with high statistical significance.

There was also a clinically significant improvement in the muscle weakness score, which the company hopes will reassure doctors about its effectiveness when deciding whether or not to prescribe it.

The trial also met secondary endpoints of triple-timed “up and go”, and muscle weakness in limb domains. A most bothersome symptom endpoint showed a positive trend but was not statistically significant.

Patrick McEnany

After last year’s failed attempt to convince the FDA with immature data Catalyst’s president and CEO, Patrick McEnany, said the company is on track to refile the drug with the FDA in the first quarter of 2018.

“We are extremely pleased with the top-line efficacy and safety results from this second phase 3 trial, which reinforces the potential of Firdapse to be an important treatment for patients suffering from LEMS. We look forward to presenting further data in future publications and at medical conferences,” he added.

Vanessa Research starts Phase 2 clinical trials in early 2018 for Shylicine™

Vanessa Research, Inc. (VRI), an emerging healthcare and biotech company, attended its first meeting with the European Medicines Agency in October and will now start its Phase 2 clinical trials in the first quarter of 2018 for the rare disease Microvillus Inclusion Disease (MVID).

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Beginning clinical trials is a tremendous accomplishment. It not only signifies the confidence in our work but it also validates that our team is on the right track in creating a treatment for MVID,” said Dr. Ludmila Kvochina, Director of Research Laboratory.

About the Clinical Trial

The primary objective of the Phase 2 clinical trials is to test the clinical activity and efficacy of Shylicine™ for the treatment of diarrhea in MVID. In addition, VRI expects to verify the reduction in patient dependency on TPN and register changes in intestinal morphology. The trial is anticipated to last 8 weeks.

 

 

Lilly looks to devices to revive diabetes division

Eli Lilly has unveiled a new partnership with diabetes device maker Dexcom to breathe new life into its diabetes division. 

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The deal will see Dexcom’s continuous glucose monitors integrated into Lilly’s Connected Diabetes Ecosystem – a portfolio of diabetes devices including smart-pens, insulin pumps, medicines, apps and software aimed at improving outcomes.

Kevin Sayer

“Lilly’s Connected Diabetes Ecosystem promises to drive a significant step forward in diabetes management. As technology converges in our industry, we believe that connected systems will become the standard of care over time,” said Kevin Sayer, president and CEO of Dexcom.

“By combining devices, drugs and technology, we can deliver solutions that adapt to each person’s unique needs in managing their diabetes while also providing compelling advancements for both physicians and payers.”

Although having been in the insulin market for some time, Lilly has been looking at ways to move into the flourishing diabetes monitoring market to fend off imminent biosimilar competition to some of its lead candidates.

In fact, according to the Wall Street Journal, Lilly has been developing an insulin delivery device and smart pen device since the opening of its Cambridge, Massachusetts lab in 2015.

When launched, the new devices will face a lot of varied competition. The new concept of the ‘artificial pancreas’ has revolutionised diabetes management thanks to the FDA’s approval of the MiniMed 670G system earlier this year.

Hailed as a milestone in diabetes treatment, the device continuously monitors blood glucose and automatically delivers insulin when needed.

Other devices of its kind will be joining the market too. Insulet’s Omnipod Horizon, the world’s first tubeless insulin delivery system, has shown promise in early trials, while closed loop systems – i.e. those that require no user interaction whatsoever – will soon follow.

Lilly has however backed Beta Bionics – a firm that is currently developing a system that delivers both insulin and glucagon, making it the closest thing to a genuine artificial pancreas yet.

Experimental opioid digital pill successful in early trial

Another ‘digital pill’ that tracks adherence to a common opioid could be on its way to market thanks to a successful initial feasibility study.

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Earlier this month, the FDA approved the first-ever digital pill in the form of Otsuka and Proteus’ Abilify MyCite.

The pill combines Otsuka’s mental health medicine Abilify with Proteus’ ingestible sensor to know when patients have taken their medication.

If a patient hasn’t done so, an alert can be sent to their doctor who can then follow up with their patient in an attempt to improve their adherence.

In this instance, the experimental medication, created by eTectRx, combines the common opioid oxycodone with a wireless ingestible sensor.

A radio frequency is emitted from the pill once it is activated in the stomach which is transmitted to a wearable and an accompanying app.

Data as to when the pill was taken is then passed onto a cloud platform which can be accessed by the patient’s care team to monitor their adherence.

In a small feasibility study carried out at Brigham and Women’s Hospital in Boston, Massachusetts, the eTectRx’s pill was given to 26 patients who had been discharged from emergency care with fracture pain.

Of the 26, 15 patients completed the study, taking a median average of six of their prescribed 21 oxycodone pills. Interviews with participants were then conducted to confirm the study’s findings.

In previous research, the pill was found acceptable by eight out of 10 users, with nine out of 10 reporting that they were willing to keep taking the pill to improve adherence monitoring.

A broader issue

In terms of feasibility, the pill worked. However, the results suggested a wider issue with opioid prescription.

In the US, opioid abuse has developed into an epidemic and has even been labelled a ‘national emergency’ by President Trump.

As the study authors note, pill ingestion varied widely among patients from three to almost ten over the study’s seven-day period. Many of the participants also took most of their pills during the first few days which then tailed off over time.

As a solution, the authors “propose that clinicians consider instructing patients to begin tapering the dose of opioid analgesics beginning at 24 hours after injury, which would also reduce the number of pills dispensed, and ultimately wasted or made available for diversion.”

Earlier this week, the FDA published guidance encouraging companies to develop generic abuse-deterrent opioid drugs as part of its drive to end the opioid addiction epidemic.

Amazon more interested in shipping medical devices… for now

Amazon is setting its sights on shipping medical devices rather than pharmaceuticals – at least for the time being.

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Earlier this year, rumours of the retail giant’s imminent entry into the medicines market arose after news broke that it had obtained wholesale pharmacy licences in at least 12 US states.

Coupled with its purchase of grocery chain Whole Foods, the suggestion was that the firm could distribute prescription drugs via these newly purchased outlets.

In response to analysts, Amazon chief financial officer Brian Olsavsky remained tight-lipped about the company’s intentions, saying he could not “confirm or deny any of the rumours related to pharmacy or anything else.”

Despite not suggesting any concrete plans, Olsavsky’s comments spooked shareholders in both Walgreens and CVS – two of the US’ biggest pharmacy chains – leading to an almost 6% share price drop for both firms.

Since then, a few reports have suggested that the company is exploring the pharmacy business as well as speaking to healthcare regulators.

More light may have just been shed on the issue though. As reported by CNBC, the online shopping giant is delaying its anticipated entry into the pharmaceutical market over concerns related to the market’s stringent regulations.

Instead, Amazon is looking to sell medical devices and supplies through its Indiana fulfilment centre for the time being, according to a Freedom of Information Act request by US investment firm Jefferies.

“Applicant (Amazon) will not store or ship drugs,” the application states.

Of course, tackling the simpler aspects of the healthcare market first, like shipping medical equipment and devices, does not mean it will now eventually take on the pharmacy market.

One idea is that Amazon could use its licenses to act as a pharmacy benefits manager (PBM), negotiating price cuts with pharmaceutical companies and pharmacies to sell to US healthcare providers.

The move would prove lucrative for Amazon – the market is thought to be worth around $420 billion. Recent poor press surrounding PBMs and their role in drug price inflation could also open the door to cheaper drug pricing from Amazon.

Samsung Bioepis’ trastuzumab biosimilar gets EC approval for breast cancer

The European Commission (EC) has approved Samsung Bioepis’ Ontruzant, a biosimilar version of Genentech’s Herceptin (trastuzumab), for the treatment of breast cancer in early and metastatic stages and also for metastatic gastric cancer.Smart-Object

Trastuzumab, which is a monoclonal antibody, is the active substance in Ontruzant. This antibody binds with high affinity and specificity to the human epidermal growth factor receptor 2 (HER2) gene.

The binding results in the inhibition of the proliferation of tumour cells that overexpress the HER2 gene, which is considered to be one of the causes in the development of breast cancer.

Samsung Bioepis president & CEO Christopher Hansung Ko said: “Breast cancer remains the most common form of cancer affecting women. We hope Ontruzant will play an important role expanding patient access to trastuzumab across the region.

“Through relentless process innovation and an uncompromising commitment to quality, we remain dedicated to advancing one of the industry’s strongest biosimilar pipelines, so that more cancer patients and healthcare systems across Europe will benefit from biosimilars.”

Ontruzant’s approval in Europe comes after the positive opinion adopted by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) in mid-September.

The drug is the first trastuzumab biosimilar to be approved in Europe.

MSD, which goes by Merck in the US and Canada, will commercialize the Samsung Bioepis trastuzumab biosomilar.

The approval of Ontruzant from the Commission applies to all the European Union (EU) member states and the European Economic Area (EEA) member states of Norway, Liechtenstein and Iceland.

Ontruzant is now the fourth biosimilar developed by Samsung Bioepis that has secured EC marketing authorization. Previously, the company received approvals for Benepali (etanercept), Flixabi (infliximab) and Imraldi (adalimumab).

Earlier in the month, Samsung Bioepis’ trastuzumab biosimilar was approved in South Korea by the Korean Ministry of Food and Drug Safety for treating metastatic breast cancer, early-stage breast cancer and metastatic gastric cancer. In South Korea, the biosimilar is branded as Samfenet.

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