GSK-Novartis mega-deal signed-off by EC

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The European Commission has approved a GSK-Novartis M&A deal, in which GSK will purchase Novartis’ vaccines unit and Novartis will buy GSK’s oncology business.

Both firms announced the overhaul of their businesses in April. The multi-billion dollar contract will involve GSK acquiring Novartis’ global human vaccines business (except the influenza vaccines business) for $7.1 billion, and Novartis taking over GSK’s oncology business for up to $16 billion.

In a third part of the deal, GSK and Novartis will combine their global consumer health business in a new entity, over which GSK will have sole control.

Under the EU Merger Regulation the EC has a legal duty to assess mergers and acquisitions involving companies with a turnover above certain thresholds, and make sure that any arrangements would not significantly impede effective competition in Europe.

The EC had concerns that the GSK-Novartis deal would affect competition in the production of vaccines and promising oncology treatments. The Commission raised the potentially detrimental effect on competition for some vaccines.

To address this GSK agreed to sell its meningitis vaccines, Nimenrix and Mencevax, on a global basis. These are marketed outside of the US and generated annual global sales of £36m in 2013. In another condition set by the EC, GSK will also divest two Novartis diphtheria and tetanus vaccines in Italy and Germany.

The oncology tranche of the deal would also have affected competition, the Commission found, by reducing the number of companies developing and marketing two investigational skin cancer treatments, B-Raf and MEK inhibitors, from three to two.

The EC report notes that these treatments “are expected to become the standard of care for the treatment of skin cancer… [and] to reach peak sales of several hundreds of millions of euros in the next few years in the EEA”.

The Commission feared that Novartis’ purchase of GSK’s oncology portfolio, which includes B-Raf and MEK inhibitors would “lead to a duopoly between the merged entity and Roche”. It was also likely to result in Novartis abandoning its clinical trials of these treatments in ovarian, colorectal and lung cancer, which would have a ‘significant impact on innovation’.

As a condition of the deal Novartis agreed to return its rights over MEK162 to its owner and licensor Array BioPharma, and to divest LGX818 to Array. “This will ensure the worldwide development of LGX818 and MEK162 as well as the commercialisation of these inhibitors in the EEA”, the Committee report says.

The EC also signed-off another major pharma pact after concluding that Mylan’s purchase of Abbott’s generics business would not adversely affect European competition. The complex deal will mean Abbott will have a 21% share in ‘New Mylan’, which will become the parent company of Mylan and continue to operate from its base in Pittsburgh, Pennsylvania.

The Commission’s investigation found that for the majority of Abbott’s generic products no competition concerns arose. However, for five generic products in Germany, the UK and Ireland, France and Italy there are a lack of substitutable products and competitors present and low likelihood of competition.

To address these concerns, Mylan will divest its businesses and marketing authorisations in these countries. Both the GSK-Novartis and the Abbott-Mylan deals are conditional upon the companies complying with these commitments.

By Lilian Anekwe – Pharmafile online

Shire lifted by rare disease approvals

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Shire’s investigational drug for a rare neurological disease has been accepted into the FDA’s fast-track approval process.

The drug, SHP609, (idursulfase-IT, also known as HGT-2310) received an FDA Fast Track designation as a treatment for neurocognitive decline associated with Hunter syndrome, a rare genetic disorder.

SHP609 is a new formulation of Shire’s existing treatment for Hunter syndrome, Elaprase (idursulfase). It is designed to be used alongside Elaprase and administered directly into the cerebrospinal fluid.

Hunter Syndrome (also known as mucopolysaccharidosis II or MPSII) is a severely debilitating rare disease that affects 1 in 162,000 babies born. It is caused by the lack of an enzyme, and can lead to severe health problems and early mortality.

The FDA’s Fast Track program is designed to help companies to get drugs reviewed more quickly, especially drugs that “address serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs”.

Being given the designation boosts a company’s chances of getting a propriety review for a drug by granting more meetings with FDA regulators, if the clinical data is robust.

In Shire’s case it is currently enrolling patients in its Phase II/III pivotal trial to look at the effect of SHP609 children with Hunter syndrome and early cognitive impairment – who being treated with Elaprase.

“This is not only the first treatment being investigated to address the significant unmet need of slowing the cognitive decline in MPS II patients, but also the furthest a program for enzyme replacement has ever progressed,” says Philip Vickers, head of research and development at Shire.

“This Fast Track designation is further recognition of the critical need to develop new, effective therapy options for patients with Hunter syndrome with cognitive impairment.”

The Irish company also received good news from the FDA after NPS Pharma, the company Shire paid $5.2 billion for earlier this month, gained an FDA approval for Natpara (parathyroid hormone) as an additional treatment for hypocalcemia in patients with hypoparathyroidism.

In response to the NPS Pharma decision on Natpara, Shire chief executive Flemming Ornskov, comments:  “The Natpara label is in line with our expectations, and we believe this approval further validates Shire’s decision to acquire NPS Pharma, which is an excellent strategic fit allowing us to leverage our  market expertise, core capabilities in rare disease patient management, and global footprint.

“We look forward to combining our strengths with NPS Pharma to launch NATPARA in the US after the expected close of the transaction in Q1 of this year.”

By Lilian Anekwe – Pharmafile online

New vice-chair for Commission on Human Medicines

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Dr Angela Thomas has been appointed as vice-chair of the Commission on Human Medicines (CHM).

She replaces Professor Ian Weller who retired from the position and from CHM at the end of December last year.

The CHM advises on matters relating to safety, quality and the efficacy of medicines as well as the collection of adverse drug reactions.

Thomas is a consultant paediatric haematologist at the Royal Hospital for Sick Children in Edinburgh, a fellow of the Royal College of Physicians in Edinburgh, a former president of the British Society for Haematology and has been on the CHM since 2005, where she chairs the Clinical Trials, Biologicals & Vaccines Expert Advisory Group.

She has also served as a member and chaired many scientific and medical committees in the UK and Europe.

Thomas says: “I am delighted to be taking up this new role. The Commission plays a vital role in the licensing of new medicines and in monitoring drug safety.

“I have found my time as a member of CHM tremendously rewarding and am looking forward to the challenges offered in my new role as vice-chair.”

Pharmafile online

GSK double complaint ruled out by PMCPA

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Complaints questioning the promotion of two of GlaxoSmithKline’s chronic obstructive pulmonary disease (COPD) drugs have been ruled out by a PMCPA panel.

One objection accuses the UK pharma firm of trying to hide important safety information about Relvar (fluticasone furoate/vilanterol). The complainant argued that it is not made clear in any GSK marketing that the inhaler can cause pneumonia to asthma patients.

The other regards Seretide (salmeterol/fluticasone) and notes that the TORCH study – of which the device was trialled in – did not meet its primary endpoint. Despite this, promotional claims for Seretide have referred to favourable findings.

As the ruling and regulatory arm of the ABPI, the PMCPA concluded that not all marketing material for the treatment referenced secondary endpoint data from the study. But that high standards had not been maintained so a breach of Clause 9.1 – failing to maintain high standards at all times – was ruled, Clause 2 – discredit to the pharma industry – wasn’t.

The panel’s governing on Relvar concluded that information on pneumonia as a side-effect in patients with asthma is available, so did not warrant a breach of any clauses to the code. The information appears in the relevant sections of the company’s website, along with links to the Summary of Product Characteristics (SPC).

Both decisions will provide great relief to the British pharma firm which in 2012 was not so lucky, as it breached three clauses in the ABPI Code of Practice following a complaint from a member of its own staff.

GSK was found guilty of Clause 15.2 which deals with reps’ ethical conduct, after the employee protested that a representative had promoted the unlicensed use of blood disorder drug Revolade (eltromopag).

The complaint stemmed from an email sent referencing an individual funding request (IFR) for a patient. As a result the firm also breached Clauses 9.1 and 3.2, which states that the promotion of a medicine must be in accordance with the terms of its marketing authorisation.

However, the positive result from the PMCPA today for Relvar and Seretide mean that GSK can focus on the latter’s partial successor – Anoro (umeclidinium/vilanterol) – as it looks to compete in a market host to more than 21 million COPD patients.

Backed by the Committee for Medicinal Products for Human Use (CHMP) last year and given the nod in Europe just days later, the pharma firm’s new treatment – in partnership with biopharma Theravance – could generate worldwide annual sales of around $2.65 billion by 2019 according to Reuters.

By Tom Robinson – Pharmafile online

Daiichi-Sankyo pays $39m to settle allegations

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Daiichi-Sankyo will pay the US government and state Medicaid programmes $39 million to resolve claims that it violated the False Claims Act by paying kickbacks to induce doctors to prescribe its drugs.

The decision concerns the US subsidiary of the Japanese pharma giant’s offerings Azor, Benicar, Tribenzor and Welchol – The US Department of Justice (DOJ) confirmed on Friday.

“The Anti-Kickback Statute prohibits payments intended to influence a physician’s ordering or prescribing decisions,” said acting assistant attorney general Joyce Branda for the civil division in DOJ.

The government alleged that Daiichi paid doctors improper kickbacks in the form of speaker fees as part of its ‘Physician Organization and Discussion’ programmes, known as ‘PODs’.

These were run from the beginning of 2005 through to March 2011, alongside other speaker programmes that were run around the same time period.

Allegedly, payments were made to doctors even when doctor participants in PODs took turns ‘speaking’ on duplicative topics over Daiichi-paid dinners, the recipient spoke only to members of his or her own staff in his or her own office, or the associated dinner was so lavish that its cost exceeded Daiichi’s own internal cost limitation of $140 per person.

“Drug companies are prohibited from using lavish entertainment and padded speaker programme payments to induce physicians to prescribe their drugs for beneficiaries of federal healthcare programmes,” says US Attorney Carmen Ortiz for the District of Massachusetts.

“Settlements like this one show that the government will continue to pursue healthcare companies that use kickbacks to promote their products.”

The settlement stems from a complaint filed by former Daiichi sales representative Kathy Fragoules under the whistleblower provisions of the False Claims Act, which authorises private parties to sue on behalf of the US, and to receive a portion of any recovery. Fragoules stands to receive $6.1 million as a result.

Agreeing also to review its internal operations with a view to reform, Ken Keller who is president of Daiichi’s US operations says in a statement: “We are pleased to have finalised these agreements and remain focussed on our core mission of helping people live healthy and meaningful lives.”

By Brett Wells – Pharmafile online

Late-stage failure for Otsuka and GW cancer pain drug

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Otsuka and GW Pharmaceutical’s multiple sclerosis drug Sativex has failed to meet the primary endpoint in its first Phase III trials in cancer pain.

Sativex (nabiximols) is derived from cannabis and usually used to treat the symptoms of multiple sclerosis (MS). This trial was testing the drug for the treatment of patients with advanced cancer where opioid therapy does not adequately reduce their pain, but it did not demonstrate a statistically significant difference from placebo.

In Phase II trials however, Sativex did show such improvements using the same primary measure as in the Phase III trial.

“Although we missed the primary endpoint in this trial, based upon the positive data seen in the Phase II programme, we remain confident in the ability for Sativex to relieve cancer pain in this patient population,” says Justin Gover, GW’s chief executive.

“We have two additional pivotal Phase 3 trials ongoing which, if positive, would still allow us to submit a New Drug Application with the US FDA. We look forward to results from these two further studies later this year.”

The second Phase III trial is expected to report top line results in the second quarter of 2015, while the results of the third are set to come in at the end of the year.

This is the second setback for Sativex in recent months, after NICE ruled that the drug was too costly to be used in England for its original indication of spasticity due to MS.

Dr Paul Cooper, who chaired the watchdog’s guideline development group, told the Guardian that “The substantial cost of Sativex […] compared to the modest benefit does not justify its use; there are better ways to improve care for people with MS”.

Sativex, the world’s first plant-derived cannabinoid prescription drug, was developed by GW with Otsuka acting as a licensing partner for the US. It is currently approved for MS in 27 countries outside the US, and a request for Special Protocol Assessment has been submitted to the FDA for a proposed Phase 3 study in this indication.

Doctor Marie Fallon, the principal investigator of the trials added: “We believe that cannabinoid therapy offers a potentially novel approach as a co-analgesic to provide pain relief beyond opioid therapy. Too many patients with advanced cancer do not attain adequate pain relief from an opioid regimen, or experience unacceptable opioid side effects.

“Whilst I am naturally disappointed that this first trial did not achieve its primary endpoint, I remain optimistic about the potential of Sativex.”

It is not all bad news for GW though – the company also announced that all of its trials for the children’s epilepsy drug Epidiolex (pure cannabidiol) are on track or ahead of schedule, with Phase III results now expected by the end of 2015.

By George Underwood, Pharmafile online

Amgen and Novartis start cancer immunotherapy push

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Amgen and Novartis have launched new licensing agreements with biotech companies that they hope will lead to the development of new cancer treatments.

The Amgen deal will see the US company partner with California-based Kite Pharma in a partnership worth an initial $60 million, which could grow to $525 million “based on the successful completion of regulatory and commercialisation milestones”.

Novartis’ agreements with Intellia Therapeutics and Caribou Biosciences, include a combination of upfront payments, equity investments and success-based royalties.

The R&D elements of the partnerships will focus on producing new cancer offerings called chimeric antigen receptor (CAR) T-cells, potential new treatments that are predicted to move into late-stage trials over the coming years.

Early-stage trials of CAR T cells featured heavily at the recent American Society for Hematology conference in San Francisco, generating excitement within the industry about their potential as treatments for some cancers, including acute lymphoblastic leukaemia and chronic lymphocytic leukaemia.

CARs are proteins that allow genetically-engineered T cells to produce special receptors on their surface, to recognise a specific protein (antigen) on tumour cells, and kill them.

Dr Sean Harper, executive vice president of R&D at Amgen, says this approach “represents one of the most promising approaches to delivering significant impact for patients with cancer.

“We believe joining forces with Kite Pharma will leverage our targets and their leading CAR T cell platform to advance another new promising therapeutic approach to fight cancer.”

While Dr Arie Belldegrun, Kite Pharma’s president and chief executive says: “We believe that the therapeutic candidates resulting from the collaboration will have the potential to dramatically transform CAR approaches and to become some of the most powerful therapies for the treatment of cancer.”

Mark Fishman, president of the Novartis Institutes for Biomedical Research, adds the collaboration gives the company access to a new genomic approach to engineering CAR T cells.

“It is now time to explore how to safely extend this powerful technology to the clinic. It has the potential to open a new branch of medicine, editing the genome to cure disease. Much remains to be learned, and we are delighted to explore these directions with colleagues from Intellia and Caribou.”

By Lilian Anekwe – Pharmafile online

Abbvie Hep C drug gains FDA approval

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Abbvie has gained sign-off for its rival treatment to challenge Gilead’s dominance of the growing market for new hepatitis C medicines.

The FDA has accepted Abbvie’s application for Viekira Pak, an oral combination treatment for patients with chronic genotype 1 (GT1) hepatitis C, including those with liver damage.

Viekira Pak (dasabuvir), contains three drugs (ombitasvir, paritaprevir and ritonavir), with three different mechanisms of action that work together to attack the virus. In Phase III trials Viekira Pak cured more than 95 per cent of people GT1 hepatitis C, which affects more than 70 per cent of all people with hepatitis C. It has been recommended with or without the generic hepatitis drug ribavirin. It is also approved for people with hepatitis C and HIV who have had a liver transplant.

Head-to-head

Abbvie has priced its drug more modestly than Gilead’s Harvoni (sofosbuvir and ledipasvir). The Viekira Pak will cost $83,319 for a 12-week course of treatment; 12 per cent cheaper than the $94,500 cost for Harvoni for the same treatment length. However Gilead estimates that some patients only need to take Harvoni for eight weeks, which reduces the per-pill cost to $63,000.

Abbvie may struggle by comparison to the Gilead drugs on compliance. The Viekira Pak regimen involves three pills in the morning and one at night, and six tablets if taken with ribavirin. This compares with once-daily Harvoni, which has similar cure rates.

Analysts predict Gilead, who launched Harvoni in December, will retain the majority of the market for new hepatitis C treatments, which is estimated to be worth $15 billion in 2015.

Pricing deals

But Abbvie has moved to guarantee a more secure market share by negotiating directly with the largest US pharmacy benefits provider.  Express Scripts, a vocal critic of Gilead’s pricing, has signed an unprecedented pact with Abbvie to provide Viekira Pak exclusively to patients at a discounted cost – to the exclusion of Gilead’s drugs.

In exchange for the discount Express Script will put no limitations on the extent of liver damage patients must have before receiving treatment. Primary care doctors will be able to prescribe Viekira Pak as well as specialists, further broadening the market.

Abbvie chief executive Richard Gonzalez says: “We are proud of the work of our research and development organization to bring this important therapy, offering high cure rates, to patients with hepatitis C. We believe appropriate patients, regardless of their fibrosis stage, should have broad market access to Viekira Pak, and we are committed to supporting access to this therapy.”

The FDA’s decision triggered a $75 million milestone payment by Abbvie to Enanta Pharmaceuticals, who developed Viekira Pak, bringing the total payments from AbbVie to Enanta to $227 million.

In Europe, the EMA has granted positive opinions for VIEKIRAX (ombitasvir/paritaprevir/ritonavir) and EXVIERA (dasabuvir) for the treatment of chronic hepatitis C. A final decision expected in early 2015.

-  Pharmafile online

Gilead sued over Sovaldi price

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A payer is suing Gilead over the price of its hep-c drug Sovaldi in the US after spending $2.4 million on the treatment for its employees.

Sovaldi (sofosbuvir) costs $84,000 per course of treatment in the country, a price that the Southeastern Pennsylvania Transportation Authority (SEPTA) claims is ‘exorbitant’ and in “sharp contrast to the prices at which Sovaldi is being made available by Gilead in other countries”.

Its suit points to Gilead’s licensing of the pill to generic companies in developing countries at a ‘deeply discounted’ price and its estimated $900 cost in Egypt as examples of this ‘obvious paradox’.

“Gilead is not authorized by the patent laws (or otherwise) to abuse its purported monopoly on Sovaldi by charging discriminatory prices that apparently have no rational basis other than to inflate the company’s bottom line,” the company adds.

“Gilead’s price gouging has had at least two detrimental consequences in this country. It has, obviously, resulted in the consumers and entities that have purchased Sovaldi paying significant prices for the drug. It has also effectively priced some consumers and government programs alike out of the Sovaldi market, thereby preventing needed recipients from obtaining this critical drug.

“Notably, there have been reports that this pricing scheme has had a disproportionately high impact on minorities and those in lower income brackets (demographics that have had historically higher incidents of Hepatitis-C infections).”

Separately, the US Senate Finance Committee is investigating the pricing of the drug and whether the market for Sovaldi ‘is working efficiently and rationally’.

Sovaldi is part a of new generation of highly effective hepatitis C drugs and has been shown to effectively cure the disease in more than 90% of patients in just 12 weeks. Gilead has said that this justifies the high cost of the drug as in the long-term it can reduce the need for costly liver transplants.

The effectiveness of the drug combined with its price tag has led to Sovaldi becoming the fastest-selling drug of all time – it made $8.4 billion in its first nine months on the market and is on course to break the $10 billion marker by the end of the year.

The question of Sovaldi’s price is not just an issue in the US, though – in October internal documents revealed that the NHS may be unable to afford the drug despite NICE previously saying that it was willing to pay for it.

Several other pharma firms, including BMS, Merck and AbbVie, have similar hep-c drugs in the pipeline. Meanwhile, Gilead’s Sovaldi combination treatment Harvoni has recently seen approval in the US and Europe.

By George Underwood – Pharmafile online

Roche submits melanoma drug to FDA

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Roche has submitted its melanoma drug cobimeinib for review with the FDA as it confirms the results of its Phase III trial.

The coBRIM study tested the MEK inhibitor combined with Roche’s established treatment Zelboraf (vemurafenib) in patients with BRAF V600 mutation-positive advanced melanoma.

The results showed that the combination therapy increased progression-free survival by 9.9 months compared to 6.2 months with Zelboraf alone.

“In the past several years we have made significant progress in treating advanced melanoma, but it remains a serious and difficult to treat cancer that affects more people each year,” says Sandra Horning, chief medical officer and head of global product development at Genentech.

“We look forward to working with the FDA as they review the NDA and hope the combination of cobimetinib and Zelboraf will soon become a new option for people with BRAF mutation-positive advanced melanoma.”

Melanoma is rarer than other forms of skin cancer, but is one of the most aggressive and deadly forms of the disease and most patients have a poor prognosis. MEK inhibitors like cobimeinib work by blocking the MEK protein and affecting signalling pathways involved in regulating cell division. These pathways are often overactive in cases of melanoma and other cancers.

Zelboraf targets another protein on this pathway – mutant BRAF – to interrupt abnormal signalling that can cause tumours to grow. It has been approved for the treatment of melanoma since 2011 in the US and 2012 in Europe.

Earlier this year GlaxoSmithKline’s own combination treatment of Mekinist (trametinib) and Tafinlar (dabrafenib) was shown to be more effective than Zelboraf in trials, but these latest results may give Roche’s drug a new lease of life.

Cobimeinib was discovered by Exelixis and is being co-developed by Roche’s Genentech subsidiary. It is also being investigated as part of a combination therapy in other cancer types, including non-small cell lung cancer, colorectal cancer and breast cancer.

Roche says that it has already submitted the data from coBRIM to the EMA.

By George Underwood – Pharmafile online