Need for new drugs driving pharmaceutical research

The need for new drugs and health products continues to rise while regulators, consumers and healthcare providers are demanding greater value for money, more transparency and access to information. The response from industry has been increased investment in R&D and innovation.

"If you look at the pharmaceutical industry in Ireland, it has largely been based on manufacturing," says Science Foundation Ireland director general Prof Mark Ferguson. "That has been changing quite dramatically. It is moving from batch to continuous manufacturing. The industry used to make a batch, test it, and then make another batch. Manufacturing is now continuous and is about sensors in the process and that makes it much more efficient. There are a lot of challenges in getting regulatory sign-off for that."

That process innovation is not the only change. “We want these companies to do more R&D in Ireland,” he adds. “And there is evidence that this is happening. The good news is that we are beginning to attract some projects.”

Of course, R&D is a risky activity. “Biology is not a predictable science,” Ferguson points out. “Physical science is predictable, that’s why very few bridges and buildings fall down. You can model them in advance and predict what will happen under various sets of conditions. Biology is not yet predictable. R&D is seriously expensive, and a lot of things tried don’t work out at the later stages after spending a huge amount of money.”

But this is beginning to change, thanks to a number of scientific developments. “There are a couple of things happening. There is increased use of artificial intelligence and machine learning to assist the process – it is hoped that this will make things more predictable. We are still some way from that goal, it is a five- to 10-year journey but it will improve. In parallel, we have the problem where the drugs don’t work. There are patient safety issues due to adverse reactions. Drugs work beautifully for some patients but not for others. By using genomics, we can find molecules that work for certain patients.”

Utilising genomic data is another issue. “It is a big numbers problem but the convergence of biology with ICT, big data, data analytics, quantum computing, electronic patient records, and gene sequencing is helping to address it,” Ferguson explains.

Trade-offs

But realising the benefits of that convergence will require certain trade-offs. "People are concerned about privacy," he continues. "What are we willing to trade off? If you and only you know your genome sequence, then it's absolutely useless. We need to trade off that data with healthcare professionals. We are willing to trade private data with Facebook, Google and others in return for free services, why not medical data? It's not just about personalised medicines. It's about finding the 30 per cent of people who a drug will work for."

Dr Patrick Buckley is director of the GMI Genomics Centre at Genomics Medicine Ireland, the company which is currently building a disease-specific database of population genomics in Ireland.

“To put it in context, when the first human genome was sequenced it took 13 years,” he says. “We can sequence 48 samples in 40 hours. This shows how far the technology has come. The cost has been driven down a lot. The original sequence cost $2.7 billion, now it’s less than $1,000 each.”

He points to a number of potential uses for genomics data. One instance is oncology, where a tumour can be analysed and the data on its DNA then used to detect tumour cells in a blood sample. This is already being used for the development of ultra-sensitive tests for the spread of cancers. “It can be used to quantify the amount of tumour cells present and that could be used to measure the patient’s response to treatment,” says Buckley. “We will see genomics data being integrated into healthcare settings in future.”

Improving the efficacy of medicines is another benefit. “We will be able to establish if a patient has a mild or severe form of the disease and what the most appropriate drug is. It may be that there are four drugs available but only two are appropriate because the patient won’t respond.”

He points to research carried out on the top 10 drugs in the US. The number one drug was effective in one in four cases while the tenth was effective in just one in 25.

Diagnostics is another application. “We are working with Temple Street Children’s Hospital to offer whole genome sequencing to children with rare diseases that are as yet unidentified,” says Buckley. “We sequence the parent and child and spot the differences between the child and unaffected parent to identify the genes involved in the disease.”

Drug discovery

And then there is drug discovery. “We are working with pharma industry partners to identify targets in the genome that could lead to new drugs.”

He points to the HER2 gene and and breast cancer. “Herceptin is a targeted personalised genomics-based medicine,” he says. “Lots of drugs in development have a genomics basis and experience shows they are twice as likely to get through clinical trials and the FDA approval process as those which are not.”

The food industry is also adapting to bring new health products to market. "Irish companies are producing products with health benefits," says Dr Philip Allsopp, lecturer in human nutrition at Ulster University.

Marketing these products is far from easy, however. "There are a couple of ways to do it," he adds. "The first is get high-calibre, well-designed scientific studies to support the claims. They accumulate a portfolio of evidence and submit a dossier to the European Food Safety Agency in order to substantiate the health claim they are making for the product. The problem is that this comes at massive financial cost and most submissions do not get approval."

The other way to go is to do the studies and use them to market the product without making definitive claims. “They can do the scientific studies, get the evidence and get the message out to consumers and industry customers.”

One study with which Allsopp was involved was with Marigot in Cork. The company harvests seaweed skeletons from the ocean floor and uses them in its products. The Ulster team was able to provide evidence that the product contains calcium and magnesium and the company is allowed to make that scientific statement.

“They can make a generic nutrition claim rather than for a direct health benefit. That’s good because they are trying to improve the health of the nation. Take vitamin D for example. Many Irish people are deficient in it. If they take a product containing vitamin D, it should be beneficial. Academic researchers are not there to provide marketing tools to industry, but good-quality science will help industry prove the composition of their products.”