23 July 2019

FDA approves nine generics of Pfizer’s Lyrica drug

The US Food and Drug Administration (FDA) has approved nine generic versions of Pfizer’s nerve pain drug Lyrica (pregabalin), which are the first generics approved for the medication.

Lyrica is a prescription medicine cleared by the FDA for the treatment of various conditions. These include fibromyalgia, spinal cord injury nerve pain, pain after shingles and diabetic nerve pain.

It is also prescribed for partial-onset seizures in epilepsy patients who use one or more drugs for seizures.

According to IQVIA, pregabalin capsules generated around $5.4bn in annual sales in the US for the 12 month period ending 31 May 2019.

The latest FDA approvals have been granted to Lyrica generics by Teva Pharmaceuticals, Alembic Pharmaceuticals, Amneal Pharmaceuticals, Alkem Laboratories, InvaGen Pharmaceuticals, MSN Laboratories, Dr Reddy’s Laboratories, Rising Pharmaceuticals and Sciegen Pharmaceuticals.

These new medications have been used to regulate neuropathic pain caused by diabetic peripheral neuropathy. Furthermore, they can also manage symptoms of postherpetic neuralgia, fibromyalgia and neuropathic pain related to spinal cord injury.

The generic versions can also be used as an adjunctive therapy to treat partial-onset seizures in people aged 17 years and above.

FDA Center for Drug Evaluation and Research director Janet Woodcock said: “Today’s approval of the first generics for pregabalin, a widely-used medication, is another example of the FDA’s longstanding commitment to advance patient access to lower cost, high-quality generic medicines.

“The FDA requires that generic drugs meet rigorous scientific and quality standards. Efficiently bringing safe and effective generics to market so patients have more options to treat their conditions is a top priority for the FDA.”

The regulator noted that pregabalin is associated with multiple warnings. These warnings include angioedema risk, hypersensitivity reactions, peripheral oedema and increased risk of suicidal thoughts or behaviour.

It may also increase seizure frequency or other adverse reactions when rapidly discontinued.

In Lyrica’s clinical trials, common side-effects included dizziness, swelling, abnormal thinking, somnolence, dry mouth, blurred vision and weight gain.

22 July 2019

Gilead gets licences to three antiviral programmes from Novartis

Gilead Sciences has secured an antiviral deal with Novartis to gain exclusive global rights to preclinical programmes involving candidates for the treatment of various viral infections.

Diseases that will be explored include herpes viruses, human rhinovirus and influenza.

The deal will enable Gilead to further its services in antiviral research and development. This will allow for the expansion and commercialisation of new small molecules against three undisclosed targets.

As part of the agreement, Gilead will make an upfront payment, along with potential additional payments of up to $291m. This will be contingent upon select development and commercial milestones.

Novartis will also be eligible to receive royalties on annual net sales of the resulting products.

In relation to the deal, Gilead chief scientific officer and research and development head John McHutchison has said: “Today’s announcement builds on Gilead’s heritage in antiviral research and development. We look forward to applying this expertise to advance the development of potential new treatments for viruses with limited therapeutic options.”

Gilead’s portfolio of antiviral products includes medications for treatment in patients with HIV, hepatitis B, hepatitis C and influenza infection.

Over the past months, Gilead formed a series of alliances to aid the expansion of its medicines portfolio.

Recently, the company extended its partnership with Galapagos with a ten-year global research and development (R&D) deal. This will provide access to new clinical and preclinical assets.

Previously, the companies have agreed to work on the development of therapies for various inflammatory diseases.

Earlier this month, Gilead and Lyndra Therapeutics entered a deal for the development and commercialisation of ultra-long acting oral drugs to treat HIV.

Gilead also formed another alliance in June to leverage Nurix’s drug discovery platform for a channel of protein degradation drugs to treat cancers and other diseases.

A three-year partnership with insitro was signed in April to develop a new artificial intelligence (AI)-based platform. This will create research into new medications for non-alcoholic steatohepatitis (NASH).

In May, the company collaborated with Goldfinch Bio on new drug candidates to treat diabetic kidney disease (DKD) and selected orphan kidney disorders.

19 July 2019

UK’s NICE backs Novartis breast cancer drug Kisqali

The UK’s National Institute for Health and Care Excellence (NICE) has approved Novartis’ drug Kisqali (ribociclib) in combination with fulvestrant for the treatment of certain patients with advanced breast cancer.

In its draft guidance, NICE recommended the combination for hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer patients who received prior endocrine therapy.

Ribociclib is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor that targets proteins in cancer cells to block their division and growth.

According to clinical trial data, ribociclib and fulvestrant combination increases the length of time before the cancer progresses compared to fulvestrant alone.

NICE noted that there was a lack of evidence on whether Novartis’ drug increases the length of survival as the final data is yet to be reported.

Based on the combination’s potential to be cost-effective, it has been recommended for use on the Cancer Drugs Fund (CDF), allowing the collection of additional data about overall survival and cost-effectiveness.

The positive opinion comes after Novartis improved its patient access scheme as part of a commercial agreement, said the committee.

NICE Centre for Health Technology Evaluation director Meindert Boysen said: “Treatments that can postpone disease progression are important because they can reduce the number of people who are exposed to the often unpleasant side-effects of chemotherapy, and delay the need for its use in others.

“We are pleased, therefore, that the company has agreed a commercial arrangement for ribociclib that will allow it to be made available to people with this type of breast cancer.”

The committee added that the therapy could help treat up to 5,300 women who have had endocrine therapy and where exemestane-everolimus is the most suitable alternative to a CDK 4/6 inhibitor.

In November 2017, NICE recommended the use of Pfizer’s palbociclib for women with previously untreated hormone receptor-positive, HER2-negative metastatic breast cancer on the NHS.

18 July 2019

Researchers develop ‘Trojan horse’ chemo drug delivery system

Northwestern University researchers have developed a drug delivery system that can disguise chemotherapy drugs as fat, meaning that tumours readily consume them, the drugs are then activated to suppress tumour growth and eventually the tumour dies.

The system is an engineered long-chain fatty acid with two binding sites on each end for the drugs, which is hidden inside human serum albumin (HSA). The body’s cellular receptors recognise the fats and proteins supplied by the HSA, and allow the fatty acid to enter cells.

Northwester University Jacob and Rosalind Cohn professor of chemistry Nathan Gianneschi, who led the research, commented: “It’s like a Trojan horse. It looks like a nice little fatty acid, so the tumor’s receptors see it and invite it in. Then the drug starts getting metabolized and kills the tumor cells.

“The idea is to disguise drugs as fats so that they get into cells and the body is happy to transport them around.”

In an animal study, the system was used to carry US Food and Drug Administration-approved chemotherapy drug, paclitaxel. The disguise system allowed the drug to enter and completely eliminate three types of cancer tumours: bone, pancreatic and colon.

Additionally, this approach reduced the toxicity and side effects of paclitaxel by almost 17 times, while allowing for a 20 times higher dose to be delivered.

Gianneschi noted: “Our goal is to increase the amount that gets into a tumor versus into other cells and tissues. That allows us to dose at much higher quantities without side effects, which kills the tumours faster.”

The study was published in Journal of the American Chemical Society and was funded by Elevance Renewable Sciences, the ARCS Foundation and the Inamori Foundation.

The first author of the study was Cassandra E Callmann, a fellow at the university and Gianneschi’s former graduate student.

17 July 2019

Gotham and Mercachem generate epitranscriptomic target library

New York-based RNA-focused drug discovery company Gotham Therapeutics and German contract research organization (CRO) Mercachem have announced they have created a high-quality compound library focused on epitranscriptomic drug discovery.

The collaborative library contains 2,000 analogues and more than 80 distinct chemotypes, which are privileged structures for binding to epitranscriptomic targets, and therefore support structure and scaffold-based drug design.

This library is expected to help Gotham continue its drug discovery efforts in the epitranscriptomics space. The company has been working in this area since 2012, when co-founder Samie Jaffray advanced the concept that messenger RNA (mRNA) regulation was influenced by epitranscriptomic modification.

Gotham Therapeutics chief scientific officer Dr Gerhard Müller said: “Together with Mercachem, we have developed a unique approach to identify small-molecule master keys that are able to unlock novel targets and address the specific pharmacophoric features this target family shares.

“This targeted library further strengthens our drug discovery engine and will be repeatedly explored as we continue our collaboration with Mercachem in all future pipeline projects along the hit-to-lead candidate trajectory.”

Mercachem managing director Dr Frank Leemhuis said: “The growing epitranscriptomic-directed compound collection will enable Gotham to more rapidly advance drug discovery projects against novel targets.

“We look forward to seeing the progress Gotham aims to make in the epitranscriptomic space with the assets and know-how gleaned as part of our collaboration.”

This builds upon Gotham, alongside Dutch CRO ZoBio, identifying the METTL3/METTL14 complex as its lead therapeutic candidates in March this year. This complex is a SAM-dependent methyltransferase, which modifies mRNA and regulates protein expression.

Müller commented: “With METTL3/METTL14 being among the more obvious approaches in epitranscriptomics, the quality of the chemical matter pursued is going to be a key differentiating factor.

“Together with ZoBio, we have not just successfully identified the initial candidates for Gotham’s first pipeline programme but also established a robust process from gene to lead as a platform for additional projects to come.”

Gotham is focusing its drug discovery programmes on a few indications, including cancer, auto-immune disorders, viral infections and neurodegenerative disorders.

16 July 2019

Oklahoma seeks $17bn from J&J for opioid crisis

Lawyers for the US state of Oklahoma have argued that Johnson & Johnson (J&J) should be held responsible for driving opioid epidemic in the country and pay around $17bn over 30 years to address the crisis.

The lawyers, including Attorney General Mike Hunter, said that the pharmaceutical giant carried out a marketing campaign that created confusions about the risks of its addictive pain medication, reported Reuters.

According to state attorney Brad Beckworth, J&J downplayed the addiction risks that led to over-prescription of the drugs, fuelling the epidemic.

However, the company denied the accusations and argued that it offered medications regulated by the US Food and Drug Administration (FDA) to people suffering from chronic pain.

J&J’s lawyer Larry Ottaway further noted that the state did not provide evidence from any local doctors to support allegations that the company and its subsidiary Janssen misled them about the addiction and overdose risks.

Judge Thad Balkman is expected to issue a verdict for the non-jury trial by the end of next month.

This case is the first of approximately 2,000 lawsuits filed by state and local governments against drugmakers for fuelling the opioid epidemic. J&J is the first company to face trial.

In March this year, Purdue Pharma signed a $270m settlement agreement with the state of Oklahoma to resolve an opioid lawsuit. This was followed by Teva’s $85m settlement in May over illegal marketing of the company’s pain medication in Oklahoma.

In June, Insys Therapeutics agreed to pay $225m to settle the criminal and civil probes by the US Department of Justice (DoJ) involving its opioid painkiller Subsys.

Moreover, Reckitt Benckiser agreed to pay up to $1.4bn to the DoJ and the Federal Trade Commission to resolve the opioid probe against its former unit Indivior.

15 July 2019

Gilead and Galapagos deepen R&D alliance with ten-year deal

Gilead Sciences has expanded its partnership with Belgian biotech company Galapagos with a ten-year global research and development (R&D) deal.

The companies initially partnered in 2015 to develop new drugs targeting inflammatory diseases, including filgotinib for rheumatoid arthritis (RA) and Crohn’s disease.

The extended deal will give Gilead access to new Galapagos compounds, including six molecules undergoing clinical trials and more than 20 preclinical programmes.

Gilead will also be able to use Galapagos’ research base, more than 500 scientists and a drug discovery platform, which is based on disease-related, human primary cell-based assays.

In turn, the company will make a $3.95bn upfront payment to Galapagos, along with a $1.1bn equity investment.

Galapagos intends to use the proceeds to expand and accelerate its research and development programmes.

Under the latest agreement, Gilead will gain an exclusive licence and option rights for the development and commercialisation of all existing and future programmes globally, except in Europe.

The company receives rights to a Phase III candidate for idiopathic pulmonary fibrosis, GLPG1690, as well as option rights to Phase IIb candidate GLPG1972 for osteoarthritis in the US.

Gilead Sciences chairman and CEO Daniel O’Day said: “We chose to partner with Galapagos because of its pioneering target and drug discovery platform, proven scientific capabilities and outstanding team.

“Gilead also gains exclusive access to all current and future compounds in Galapagos’ rich pipeline while Galapagos is able to expand its research activities and build commercial infrastructure.”

All discovery and development activities will be funded and lead by Galapagos until the completion of Phase II, when Gilead may acquire an expanded licence to the compound.

If Gilead decides to exercise the option, the compound will be co-developed and the companies will share costs equally.

Galapagos is eligible for an additional $325m if GLPG1690 receives the US regulatory approval.

In the case of GLPG1972, Gilead has an option to licence the compound for $250m in the US after the ongoing Phase IIb osteoarthritis study ends. The agreement also covers additional payments at certain other milestones of the compound.

Galapagos will receive a $150m opt-in payment per programme for all other programmes, without any subsequent milestones. The company will also receive tiered royalties on all products licensed by Gilead.

12 July 2019

US researchers develop ‘EpiPen’ to treat injured spinal cords

Researchers at the University of Michigan in the US have developed a nanoparticles injection to prevent the immune system from overreacting to trauma in order to potentially prevent paralysis from certain spinal cord injuries.

Calling the injection an ‘EpiPen’ for central nervous system trauma, the team said that nanoparticles interrupt and redirect immune cells away from the injury. In addition, cells reaching the spinal cord are modified to be more pro-regenerative.

Testing in mice showed that the injection boosts healing via reprogramming of aggressive immune cells.

In case of a spinal injury, the body’s immune response results in immune cells producing high inflammation for the neural tissues. This causes neuron death, damage to the insulating sheaths surrounding the nerve fibres and results in a scar that blocks nerve cell regeneration in the spinal cord.

In turn, the mechanism leads to loss of function below the injury level, including paralysis and loss of sensation.

With the new injection, nanoparticles reprogramme the physical characteristics of immune cells. The treatment does not contain any drugs.

It is expected that the non-pharmaceutical approach will prevent unwanted side-effects.

In addition, fewer immune cells at the trauma location would result in less inflammation and tissue deterioration.

Researchers added that immune cells that reach the injury are less inflammatory and could support tissues that are trying to regenerate.

Along with spinal cord injuries, this approach is expected to enable new therapeutic strategies for patients with various inflammatory diseases.

University of Michigan biomedical engineering professor Lonnie Shea said: “The immune system underlies autoimmune disease, cancer, trauma, regeneration, nearly every major disease.

“Tools that can target immune cells and reprogramme them to a desired response have numerous opportunities for treating or managing disease.”

Research has been published in the Proceedings of the National Academy of Sciences journal.

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