Drug research programmes that were once deemed unviable because they were likely to deliver poor returns on investment could be reactivated if gene profiling technology is adopted more widely. In doing so, pharmaceutical companies could uncover new revenue-making opportunities, which are capable of delivering lasting commercial value.
Breakthroughs in the field of ‘genome sequencing’ have made it possible to produce precision drugs to treat specific types of cancer, or other life-limiting diseases, with a relatively high degree of efficacy. In light of this, a number of drug research programmes that have been dropped while undergoing clinical trials could be revived.
One research-led breakthrough to hit the headlines involves the use of genome sequencing to isolate different strains of tuberculosis (TB), allowing the disease to be diagnosed more quickly. In particular, the technology is able to identify more complex, drug-resistant cases of the disease that would benefit from alternative medical intervention.
The actual number of drug trials that are abandoned each year before treatments reach the marketplace is unknown, at least at a global level. It is not unusual to hear about drug research programmes that fail at the final hurdle – during phase III clinical trials – because by that stage they have become an important part of the pharmaceutical company’s investment pipeline. However, it is likely that many more programmes are halted at an earlier stage, attracting little or no attention.
Why are drug research programmes halted?
Drug development programmes can be abandoned for many reasons. The most common reason is that the proposed drug has failed to meet certain specific ‘endpoints’ and is not as effective as might have been hoped – perhaps benefiting only a very small percentage of its target patients. Recent research has shown that about 50% of phase III drug trials fail to reach the marketplace for this reason. On the other hand, clinical trials could indicate that the drug has a higher than acceptable toxicity and therefore poses too much of a clinical risk. If drugs have been dropped for the former of these two reasons, they could still be worth developing further, but with a different clinical goal in mind.
Modern studies of cancer treatment efficacy have shown that there is still room for improvement. Despite research efforts, cure rates for some cancers have remained low and pharmaceutical companies have been looking for a solution. Now, growing use of genetic-profiling technologies is enabling them to look for ‘biomarkers’, such as protein indicators or genetic mutations, which could help to target both new and existing treatments more effectively.
Personalised medicine is more viable
In the past, targeted drugs, which are often complex in nature and generally only indicated for treating a subset of patients with a specific condition, have sometimes been regarded as providing too low a likely return on investment. However, as drugs like Herceptin have shown, as long as there is a high degree of efficacy in a small group of patients, such treatments can still be commercially viable. While they are costly to prescribe per dose, if fewer doses are needed because they are more effective, then there is potentially an overall cost saving for the NHS. In the case of cancer treatment, such drugs could also help to limit the use of traditional chemotherapy, which can be costly and have undesirable side effects.
Further evidencing the efficacy of precision drug treatments, a recent study by ASCO, which was carried out with 13,000 patients in 346 trials, has shown that patients experienced a significantly better outcome where genetic profiling took place.
Such studies are helping to underline the opportunity that exists for pharmaceutical companies that are prepared to delve into dropped drug trials and reconsider their market potential. Recent reductions in the cost of genetic profiling have also helped to drive interest in the development of precision drugs. Just a decade ago, it would have cost many millions of pounds to sequence the genomes of a set of patients, but nowadays it can be achieved much more cheaply. There is also more data available, providing drug development companies with a rich source of ready-made genetic information.
Patentability matters
Before investing in the reactivation of an abandoned drug development programme, pharmaceutical companies should take advice on its patentability. Even if a drug has never been sold on the open market, due to a lack of efficacy, it will very likely have been ‘disclosed’ already, which limits its patentability. In these circumstances, it might only be possible to secure a patent for the drug’s ‘use’ among a specific group of patients, rather than for the drug itself. In many countries – including the UK – it may also be possible to secure a patent for the diagnostic method used to help identify patients who are most likely to benefit from the treatment. However, such patents are currently less likely to be granted in the US, for example. As a general rule, as long as the drug in question has never been marketed, a ‘use’ claim should usually provide robust commercial protection.
A significant piece of patents case law, which remains unresolved, has led to some uncertainty however, which could be putting off pharmaceutical companies from investing in the revival of abandoned drug research programmes. Currently awaiting a possible Supreme Court hearing in the UK, the case of Warner-Lambert v Actavis will determine what conditions have to be met for a medical use claim to be infringed. The complex nature of the case has led to misunderstandings about its potential implications, however. While the case is expected to determine the viability of some secondary use claims, pharmaceutical companies can remain confident that as long as a drug under development has never been marketed and has not achieved any prior regulatory approval, then a patent secured on its ‘use’ should still be a valuable commercial asset.
In fact, in light of Warner-Lambert v Actavis, pharmaceutical companies should be actively pursuing opportunities to revive abandoned drug research programmes. Such research activity may be more likely to produce drugs with strong IP protection than investing in new uses for existing, approved drugs, the patents for which may not be as strong in the future. Furthermore, this strong IP protection can be in addition to any protection provided by regulatory exclusivity provisions, which apply in many major markets.
Strategic planning is required
Of course, reviving an abandoned drug research programme requires strategic planning. In the first
instance, it is important to select the right drug research programmes to bring back to life, avoiding those that have been dropped for safety reasons.
It is also important to evaluate the market opportunity by considering whether there are a sufficient number of patients to justify the investment. Furthermore, patent checks should be carried out to confirm that it is possible to protect a potential use claim and – very importantly – that ‘freedom-to-operate’ can be achieved. Depending on the findings of these investigations, it may be necessary to work collaboratively with the company that was involved in the original drug research programme in order to proceed without infringing existing patents, and to apply existing knowledge and accelerate the way to market.
Collaborations bring with them their own considerations of course. It will be necessary for the parties involved to sign non-disclosure agreements at the outset to ensure that any knowledge tabled during early stage meetings is ring fenced. Prior to joint activity getting underway, as well as agreeing how the programme will be funded, it is important to establish who will own any future intellectual property rights obtained for new drug treatments that are developed. Such profits may be eligible for Patent Box tax relief in the UK, which should also be taken into account.
In summary, pharmaceutical companies looking to bolster their product portfolios and drive shareholder value should look beyond quick wins in the form of secondary uses for existing drugs. Making use of increased access to genetic profiling technologies and collaborating to revive abandoned drug research programmes could deliver a fresh wave of promising precision medicines capable of extending patient survival rates and delivering a better quality of life.