GSK fined £37.6m for ‘pay-for-delay’ paroxetine deals

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GlaxoSmithKline (GSK) has been fined £37.6m for entering into deals that delayed the entry of generic versions of its ‘blockbuster’ antidepressant Seroxat (paroxetine) into the UK market.

The UK’s Competition and Markets Authority (CMA) has issued fines totalling £44.99m for anticompetitive behaviours related to the case, with smaller fines being imposed on Generics (UK) Ltd. (GUK) and Alpharma Ltd.


GSK agreed to make payments and other “value transfers” totalling over £50m to suppliers of generic medicines, including GUK and Alpharma, to delay entry of their paroxetine products between 2001 and 2004. The agreements were reached just before GSK was due to take the companies to court on the grounds that the generic products would infringe GSK’s patents of Seroxat.

The CMA says the “pay-for-delay” agreements deferred the potential competition benefits of the generics being available in the UK and that the move had particular impact on the NHS, depriving it of “significant” price falls.

When generic versions of Seroxat eventually became available in the UK in 2003, the average price of paroxetine dropped 70% in two years.

GUK and Merck KGaA, the former parent company of GUK, were fined £5.8m for competition law infringements. In respect of Alpharma’s infringement, total fines of £1.5m were imposed on Actavis UK Ltd. (formerly Alpharma Ltd), Xellia Pharmaceuticals ApS (formerly Alpharma ApS) and Alpharma LLC (formerly Zoetis Products LLC, Alpharma LLC and Alpharma Inc).

SOURCE: The Pharmaceutical JournalDOI: 10.1211/PJ.2016.20200708

FDA rejects Vertex’s sNDA for Kalydeco to treat cystic fibrosis in people aged two years and older

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The US Food and Drug Administration (FDA) has rejected Vertex Pharmaceuticals’ supplemental new drug application (sNDA) for Kalydeco (ivacaftor) designed to treat people with cystic fibrosis (CF) aged two and older, with one of 23 residual function mutations in the CF transmembrane conductance regulator (CFTR) gene.

The company received a complete response letter from the FDA, which stated that the agency cannot approve the sNDA in its current form.

In order to determine an appropriate path forward for the approval of the drug, the company plans to meet with the FDA.

The sNDA was based on preclinical data for ivacaftor in residual function mutations, the established clinical profile of Kalydeco and on previously reported data from an exploratory Phase IIa trial.

The company noted that in 19 of the 24 patients enrolled in this trial, eight of the 23 mutations proposed in the sNDA were represented.

Vertex executive vice-president and chief medical officer Jeffrey Chodakewitz said: “Our intention with this submission was to rapidly bring Kalydeco to additional people with CF who we believe may benefit.

“We chose to pursue this approach given our strong belief in the science of CF, and in the well-established safety of Kalydeco across many different groups of people with CF.

“We are disappointed by this decision and look forward to discussing with the FDA the next steps to bring Kalydeco to people with CF who have these residual function mutations.”

CF is caused by defective or missing CFTR proteins resulting from mutations in the CFTR gene and it results in poor flow of salt (chloride) and water into and out of the cell in a number of organs, including the lungs.

In 2013, the FDA granted breakthrough therapy designation for Kalydeco and is currently approved in the US to treat people with CF ages two and older who have one of the G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R or R117H mutations in their CFTR gene.

The company noted that Kalydeco is not for use in people with CF due to other mutations in the CF gene and is not effective in patients with CF with two copies of the F508del mutation (F508del / F508del) in the CF gene.


Ireland’s Shire acquires US biotech Dyax for $5.9bn

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Irish drug-maker Shire has expanded its hereditary angioedema (HAE) portfolio with the acquisition of US biopharmaceutical firm Dyax for $5.9bn.

Dyax is mainly focused on the development of plasma kallikrein (pKal) inhibitors to treat HAE, a debilitating and sometimes life-threatening rare genetic disease.

Under the deal, the Irish firm paid $37.30 in cash per each share of Dyax’s common stock. Shire will gain access to Dyax’s lead pipeline product, DX-2930, and Kalbitor (ecallantide), which are designed to treat HAE.

DX-2930 is a Phase III-ready asset that offers potentially transformative prophylactic therapy for HAE and Kalbitor is approved for HAE acute treatment in patients 12 years of age and older.

In addition, Dyax shareholders may receive an additional cash payment of $4 per share contingent to approval of DX-2930, which adds up to potential additional consideration of around $646m if the drug gets approved.

The deal was announced in November last year and was subject to Dyax shareholders approval and customary closing conditions.

Shire chief executive officer Flemming Ornskov said: “We are excited to complete the acquisition of Dyax and look forward to working alongside their very talented and committed team to address significant unmet patient need around the world.

“The addition of Kalbitor and DX-2930 to our portfolio strengthens our leadership position in HAE and, along with the commercial and research and development expertise at Dyax, is a clear strategic fit for us that advances our position as the global leader in rare diseases.

“We are confident that our patients, particularly those with HAE, will be served for many years to come.”

After securing approval from the US Food and Drug Administration (FDA), DX-2930 is expected to be launched into the market in 2018.

DX-2930 is a fully humanised monoclonal antibody targeting pKal with proof-of-concept Phase IB efficacy data, which showed a reduction of more than 90% in HAE attacks compared to placebo in the 300mg / 400mg arms in patients, with more than two attacks in the three months prior to study entry.

If approved, DX-2930 has the potential to expand HAE-treated patients and achieve annual worldwide sales of up to $2bn with exclusivity beyond 2030.


Clinigen tipped to become “global healthcare leader”

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Clinigen has high hopes following two major acquisitions

The benefits of two major acquisitions will begin to be felt in Clinigen’s (LON:CLIN) financial second half, according to City broker Peel Hunt, which reckons chief executive Peter George and his team are building a global healthcare leader.

The comments came in the wake of a first-half trading update that showed the business is firing on all cylinders.

However, the real benefits from its £225mln purchase of Idis, a specialist in the ethical supply on unlicensed medicines, and Link Healthcare, which has become part of Clinigen’s managed access division, are only starting to be felt.

Its global footprint will expand thanks to a global alliance with NASDAQ-listed Cumberland Pharmaceuticals, experts also pointed out.

The trading updated for the six months ended December revealed revenues and gross profit advanced 116% and 100% respectively, boosted principally by those recent acquisitions. Organically, gross profits were up 4%.

“Clinigen has been through a transformation over the last 12 months and is well set to develop its global footprint,” said Peel Hunt analyst Charles Hall.

“Unsurprisingly during a period of substantial change the rate of organic growth has slowed.

“However, there are clear signs of a stronger performance in the second-half (both organic and timing) and the rate of new business wins is encouraging.”

Clinigen is essentially four different companies under one roof, although there are synergies between the component parts.

Clinical trial services essentially does what it says on the tin – it supplies drugs for clinical trials.

There is an ethical dimension to Clinigen in that it provides managed access and global access programmes for drugs, so it might find and distribute medicines for compassionate use. “Wherever they are, we can deliver treatments quickly, efficiently and, most importantly, ethically,” Clinigen’s web site says.

Global access allows a medicine not yet commercially available, or is experiencing temporary supply problems, to be distributed to those in need.

Finally, Clinigen has a niche drugs arm for products that don’t fit into the portfolio of mainstream pharmaceutical companies. This business provided the strongest growth in the first half.

According to Peel Hunt, the Clinical Trials unit will deliver a decent performance for the full-year thanks to a number of new client wins. The Managed Access pipeline, meanwhile, is reported to be excellent.

Investors should also begin to detect “greater impetus” from the Global Access operation, the broker said.

Peel Hunt is predicting Clinigen’s underlying earnings (EBITDA) will be £23mln in the first half, giving pre-tax profits of £21mln.

For the full-year, pre-tax profits will be £50.5mln on sales of £373.5mln and up from £31.1mln a year earlier.

The dividend, 3.4p in 2015, is expected to grow to 3.7p, then 4p, the broker reckons.

The stock has outperformed the wider healthcare market over the past year by some margin as it has increased a quarter in value, but at 619p a share it still has some to go. Peel Hunt has a price target of £10.

The specialist healthcare boutique, Stifel, points out the Clinigen currently trades at a 10% discount to speciality pharma sector, which it says is unwarranted.

It has a ‘buy’ recommendation underpinned by an 800p a share price target.

“These results reflect the transformation of Clinigen over the past twelve months,” said Stifel’s Max Hermann, echoing the comments of Peel Hunt.

By Ian Lyall


Licence allows electronic cigarettes to be prescribed on NHS

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THE Department of Health has given the go-ahead for e-cigarettes to be prescribed on the NHS, with one of the world’s biggest tobacco companies in line to be the first supplier.

E-Voke, the ecigarette produced by British American Tobacco, has been granted a licence by the Medicines and Healthcare Products Regulatory Agency (MHRA), the UK medicines regulator, that allows it to be marketed as a smoking cessation device.

They cost about £20 and replacement cartridges are about £10 a week. A week’s supply of nicotine patches and chewing gum costs between £10 and £13.

One in 20 Scots uses e-cigs but BMA Scotland have backed a ban on them in public places and sale to under-18s.

Dr Andrew Thomson, a GP in Tayside and a member of the BMA’s Scottish Council, said: “Further research is needed to learn more about the long-term effects of electronic cigarettes to uncover whether they are an effective and safe way of reducing tobacco harm.”

BMA Scotland said it was up to individual GPs to decide whether to prescribe e-cigarettes to patients.

Dr Jean Turner, a patron of the Scotland Patients Association, said she would prescribe them if she was still a GP.

She said: “If you spend money now helping people getting off cigarettes, it will save them a lot of misery in the long term and save the NHS money treating people with vascular and lung disease.”

By Christopher B Taub


GSK’s Nucala gets marketing authorisation in Europe to treat eosinophilic asthma

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The European Commission (EC) has granted marketing authorisation for GlaxoSmithKline’s (GSK) Nucala (mepolizumab) as an add-on treatment for severe refractory eosinophilic asthma in adults.

Nucala is a biologic therapy that targets interleukin-5 (IL-5), which plays a major role in regulating the function of eosinophils, an inflammatory cell known to be important in asthma.

The drug is administered as a 100mg fixed-dose subcutaneous injection every four weeks, in addition to the patient’s normal respiratory medication, which includes high-dose inhaled corticosteroids plus additional medicines such as oral corticosteroids.

Nucala is currently approved for use in the 31 European countries covered by the European Medicines Agency (EMA).

GSK Global Respiratory Franchise head and senior vice-president Eric Dube said: “The marketing authorisation of Nucala in the EU is a significant treatment advance for appropriate asthma patients and reinforces GSK’s leadership in respiratory.

“We are proud that our work in this area, to better understand the specific role eosinophils play in severe asthma, has resulted in the licensing of mepolizumab as the first anti-IL-5 biological treatment. We aim to offer this medicine to patients as soon as possible.”

The approval is based on data from Phase IIb/III clinical development programme which investigated the efficacy and safety of mepolizumab in patients with severe asthma.

All patients in trials MEA115588 (MENSA) and MEA115575 (SIRIUS) had peripheral blood eosinophil levels greater than or equal to 150 cells/µL at initiation of treatment or greater than or equal to 300 cells/µL within the past 12 months.

University of Oxford professor Ian Pavord said: “Patients with severe refractory eosinophilic asthma are not the typical ‘asthma’ patients many people are familiar with. Despite taking high doses of inhaled medications, they struggle to control their asthma. They have particular problems with frequent asthma attacks and can require hospitalisation.

“Many also take oral corticosteroids to control their symptoms, which we know can lead to side-effects that patients often find very difficult to deal with. To be able to offer these patients a treatment that specifically targets the underlying cause of their disease will be an important option.”

The programme involved nine studies and a total of 915 subjects with severe refractory eosinophilic asthma who received either a subcutaneous or an intravenous dose of mepolizumab during clinical studies of 24 to 52 weeks duration.


FDA Approves New Drug to Treat Skin Cancer

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The U.S. Food and Drug Administration has approved a new therapy treatment for skin cancer, specifically metastatic melanoma.

The drug combination, which was partly developed at UCLA, has shown promise in treating this kind of skin cancer or melanoma without causing a secondary skin cancer.

This combination of drugs has a very high success rate particularly for patients with a BRAF mutated melanoma with lower risk of adverse side effects. The drugs have been tested at UCLA and in 135 other sites around the US, Europe, Australia and Russia.

Skin Cancer Treatments Are Scarce

The drug vemurafenib, also known as Zelboraf, was combined with cobimetinib, or Cotellic, and given to 495 patients with BRAF V600, a mutation-positive advanced skin cancer or melanoma. Patients saw such a tremendous improvement that the study was continued, and the FDA granted it Priority Review status, which led to the drug being approved.

These New Treatment Prevents Secondary Skin Cancer From Forming

Currently, 70,000 Americans are diagnosed with skin cancer or melanoma per year, and 8,000 of these people die from the disease. Half of the Americans diagnosed have a mutated proten called a BRAF mutation, which is treated with vemurafenib. By combining it with cobimentinib, not only does the drug therapy block the signal for the melanoma to grow as a cancer, but it can also prevent any other skin cancers from forming.

By Pich


Major pharmaceutical company to move into AstraZeneca site

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A MAJOR pharmaceutical company is set to move into the former AstraZeneca site in Loughborough – creating around 180 jobs over the next five years.

Almac Group, which has its headquarters in Craigavon, Ireland, has confirmed a £16m investment to expand its services to meet ongoing client demand in Loughborough.

The Almac Group provides all of the services required to take a new drug or compound from concept right though to final patient delivery.

This includes discovery, research, development and manufacturing.

In Loughborough, the company will be involved in the development and manufacture of drug products to be used during clinical trials.

These drug products are usually developed into tablets and capsules which are both stable and acceptable for human consumption during these trials.

The company has successfully completed negotiations to operate “a significant proportion” of the 69-acre site, which was formally occupied by AstraZeneca – Loughborough’s biggest employer.

This will be Almac’s first facility in England.

Specifically, Almac will occupy the formulation development and analytical testing facilities at the site.

Recycling company Jayplas acquired the 69-acre site in 2012 with a plan to develop the facility into a leading UK science park known as The Charnwood Campus.

Almac has now commenced recommissioning of the facilities with operations focusing initially on expanding both “non-potent and potent solid oral dose processing”.

It is anticipated that approximately 180 new jobs will be created over the next five years adding to Almac’s global workforce which currently stands at more than 4,000 people.

They are set to move into the site by early 2017.

Graeme McBurney, managing director at Almac Pharma Services said: “As we experience increased client demand for our pharmaceutical development and niche commercial manufacturing services, this latest expansion will significantly enhance Almac’s offering, increasing capacity and capability and further demonstrating our continued commitment to support our global clients in the development and manufacturing of their drug products.”

By Matt Jarram

AstraZeneca diabetes drug combination faces delay after FDA rebuff

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U.S. health regulators declined to approve a fixed-dose diabetes drug combination from AstraZeneca (AZN.L), delaying its launch and dealing a blow to an important plank of the drugmaker’s business.

AstraZeneca said on Friday it had received a so-called complete response letter from the Food and Drug Administration (FDA) stating that more clinical data were required before it could approve the combination of saxagliptin and dapagliflozin.

Such letters typically outline concerns and conditions that must be addressed to gain U.S. approval and the move means AstraZeneca faces an unspecified wait in getting its potential blockbuster drug cocktail to market.

Deutsche Bank analyst Richard Parkes said the FDA move probably reflected lack of data on the new formulation rather than safety or efficacy concerns and it seemed likely a launch would simply be delayed by between 12 and 24 months.

Morgan Stanley analysts said a best-case scenario was an 8-10 months’ delay but this could extend to a few years if new clinical trials were needed.

Last year, during its defence against a $118 billion takeover attempt by Pfizer (PFE.N), AstraZeneca predicted the saxagliptin and dapagliflozin fixed-dose combination could generate peak annual sales of $3 billion, out of total diabetes revenue of $8 billion expected by 2023.

Shares in the company were flat by late morning, underperforming a 1.5 percent rise in the European drugs sector .SXDP.

AstraZeneca said the FDA wanted to see more clinical trial data from ongoing or completed studies and it might also require information from new studies.

The individual component drugs in the new mix are already approved and marketed for the treatment of type 2 diabetes, under the brand names Onglyza and Farxiga, and the FDA move is not expected to affect their status, the company added.

Sales of Onglyza reached $391 million in the first half of 2015, with recently launched Farxiga selling $205 million.

Onglyza is a type of diabetes medicine known as a DPP-IV inhibitor, similar to Merck’s (MRK.N) highly successful Januvia.

Farxiga belongs to a newer drug class called SGLT2 inhibitors, which have created great excitement since a clinical trial last month showed that Eli Lilly’s (LLY.N) Jardiance slashed deaths in patients at risk of heart attack and stroke.

 Source: Reuters

(Editing by William Hardy, Jane Merriman, Adrian Croft)

CU Cancer Center study reports ‘robust antitumor activity’ of TAK-733 drug in mouse models of colorectal cancer

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A University of Colorado Cancer Center study recently published online ahead of print in the journal Oncotarget reports “robust antitumor activity” of the drug TAK-733 in cells and mouse models of colorectal cancer. In all, 42 of 54 tested cell lines were sensitive to the drug, as were 15 of 20 tumors grown on mice from patient samples. Nine of these patient-derived tumors showed regression, meaning that tumor tumors shrank in response to the drug.

“This was a large preclinical study that showed good activity for the drug and gave preliminary evidence for a potential biomarker that could predict which tumors would respond best to the drug,” says Christopher Lieu, MD, investigator at the CU Cancer Center and assistant professor of medical oncology at the University of Colorado School of Medicine.

Specifically, the drug intercedes in the MAPK signaling pathway, a cascade of cellular communication that controls cell growth and survival and is frequently altered in many cancers (especially including melanoma, non-small cell lung cancer, and colorectal cancer). The drug does this by silencing an essential link in this signaling chain, namely the molecule MEK. Without activity of the MEK kinase, MAPK signaling cannot occur and instead of surviving and proliferating, cancer cells dependent on this pathway die.

A handful of successful MEK kinase inhibitors exist, including trametinib and selumetinib.

“The preclinical results for TAK-733 were fairly impressive. We had high hopes that TAK-733 could be a next-generation MEK inhibitor that might support or replace the use of current drugs,” Lieu says.

The study seemed a perfect precursor to a human clinical trial of TAK-733 in colorectal cancer.

“However, as dramatic as some of the responses were, the drug has had some challenges in development when used in the context of a real, human body,” says Lieu.

Some promising cancer drugs are derailed by the existence of harmful side-effects. This is not necessarily the case for TAK-733. Instead, another necessary step for drugs seeking human clinical trials that could lead to approval is the consistency of the drug’s “pharmacokinetics”.

“When you give a patient ‘x’ amount of a drug, we need to know that ‘y’ amount of it will become bioavailable to cells,” Lieu says.

In this study, it seemed as if the drug’s path through the body was uneven. To Lieu’s point, “x” amount of the drug did not always lead to “y” amount of absorption or bioavailability, nor to a specific process the body used to metabolize and excrete the drug.

In Lieu’s opinion, targeting the MAPK signaling pathway in colorectal cancer remains extremely promising and doing so by silencing the MEK kinase remains an attractive target. In fact, Lieu hopes to push forward with research into possible uses of MEK inhibitors in combination with other targeted therapies for the treatment of colorectal cancer. However, as is so frequently the case in cancer science, the road from this drug’s preclinical promise to its possible clinical success appears as if it will be longer and more winding than researchers hoped.

“It’s not just the activity of a drug that matters, it’s the safety and tolerability and bioavailability,” Lieu says.


University of Colorado Anschutz Medical Campus /