Immunotherapy: The three major treatments that are changing cancer prognoses

The promise of Immunotherapy as a game-changer for cancer treatment has been evident since its advent in the space. However, 2016 was the year where it really came to the fore. We examine the leading immunotherapies in the market and their development as we move further into 2017.

From the moment of the first indication for a first-line treatment, immunotherapy became the go-to treatment for a select group of patients, and the results it demonstrated were more than encouraging – even if they were only available to specific candidates for treatment.

Immunotherapy is still in its early days, with news breaking on an almost daily basis indicating where the future of this treatment may lie and with new indications appearing regularly. Two of the major medicines in the field are Keytruda, developed by MSD (known as Merck in the United States and Canada) and Opdivo, developed Bristol-Myers Squibb – both of these medicines were given approval for the treatment of certain cancer indications in 2014, in the US – Keytruda on 4 September and Opdivo on 22 December.

Opdivo is the global market leader in terms of revenue; it raced to an early lead with indications in melanoma, second-line non-small cell lung cancer (NSCLC), renal cell carcinoma, classical Hodgkin lymphoma, and squamous cell carcinoma of the head and neck. This raft of indications sent its global sales beyond that of Keytruda, despite MSD’s product being the first to gain approval in advanced melanoma. Opdivo’s future had looked secure, with Keytruda and a further rival, Roche’s Tecentriq, not having the same market impact.

Opdivo initially brought in close to $1 billion in global sales in 2015, and moving into 2016 this figure jumped to $3.8 billion. MSD’s Keytruda, by comparison, had global sales reaching $566 million in 2015 and $1.4 billion by 2016. Tecentriq, released only last year, brought in $157 million.

However, the reality is rarely as simple as sales figures suggest, and there are some big movements behind the scenes. Most notably and against all industry expectation, Opdivo took a huge hit last August when it failed in Phase 3 trials to improve progression-free survival when used as first-line treatment for Non-Small Cell Lung Carcinoma (NSCLC).  This is significant because, months later, Keytruda was awarded first-line approval for metastatic NSCLC in October 2016.

This was the point when the battle between the top three medicines began to take off. Keytruda now has the potential to increase first-line NSCLC treatment options in those that express high levels of PD-L1. Meanwhile, in its annual financial report, BMS conceded that Tecentriq has begun eating into its market share.

With regards to Keytruda there is now a debate as to whether Opdivo can any longer be considered the market leader. Keytruda is expected to rapidly gain ground on Opdivo in terms of global sales, having gained regulatory approval as monotherapy for the first-line treatment of metastatic NSCLC in adults with appropriate tumour types. It is notable how quickly MSD has moved within the UK market, now commanding a leading position – an achievement which Ben Lucas discusses with us here at Pharmafocus.

Tecentriq, meanwhile, managed to race to the indication of the treatment of bladder cancer, in the US, and established itself as the leader in this particular field whilst expanding its own indication to include NSCLC - an important indication given the size of the global market, with it expected to grow from $5.1 billion in 2013 to $7.9 billion by 2020.

In light of these recent developments, we approached figures from Roche and MSD to offer commentary on where their upcoming immunotherapies treatments stand and how they view the developing field of immunotherapy.

Dr Maxwell Summerhayes, Senior Medical Manager, Roche

"We believe that, based on two approaches developed by Roche scientists, the future treatment landscape will be a much more personalised one that will likely include both monotherapy and combination treatments (targeted agents, chemotherapies and other immune molecules) assigned to a person’s own immune profile, allowing us to tailor the treatment to an individual’s own immune biology.

Roche has a major commitment to researching and developing cancer immunotherapy and our personalised cancer immunotherapy R&D programme comprises more than 20 established and investigational candidates, 12 of which are in clinical trials.

As our understanding of the immune system and tumour biology expands, so does our hope for developing treatments that may change people’s lives.  In recent years progress has been made in developing cancer immunotherapies that target specific aspects of an individual’s tumour. In the future, combinations of different treatments will hopefully advance this even further. This is an extremely complex area of research but is one that is being investigated now with progress being made; the future of cancer immunotherapy is an exciting one.

We have been extremely encouraged with the results from our studies with Tecentriq and with the approvals that have been granted following our filing applications. Fundamentally, these successes have been built on our deep understanding of the immune biology and the totality of our comprehensive suite of studies across a broad range of tumour types. Data in second line advanced non-small cell lung cancer (NCSLC) and bladder cancer have demonstrated that PD-L1 non- and low-expressors can potentially benefit from Tecentriq; currently there are no cancer immunotherapies reimbursed for these patient groups.

Tecentriq is currently being trialled in multiple indications in more than six different cancers. Throughout late-stage trials, we hope to secure marketing authorisation in a number of different cancers and a variety of different indications within each cancer type. This demonstrates the belief we have in Tecentriq and the potential benefit that immunotherapies could bring to a multitude of patients.

In January of 2017 we were very pleased that we were able to work with the Medicines and Healthcare products Regulatory Agency (MHRA) to make Tecentriq available for patients with locally advanced or metastatic urothelial carcinoma after disease progression following one prior platinum-containing chemotherapy regimen via the Early Access to Medicines Scheme (EAMS). Tecentriq is the first immunotherapy to be made available to patients with advanced bladder cancer, reflecting the high unmet needs in this area, with no new drug treatments impacting on survival in relapsed disease for several decades.

Roche is uniquely positioned as the world’s leading oncology company with more than 50 years of experience in providing cancer medicines to patients throughout the world. Roche provides the world’s leading portfolio of cancer medicines and tests with 12 different cancer medicines across a number of tumour types; only three cancer biologics are included in the World Health Organization Model List of Essential Medicines.

Looking ahead to future, Tecentriq is currently being assessed by the European Medicines Agency for Marketing Authorisation. We expect to receive Marketing Authorisation in the second half of this year, and are working with Health Technology Appraisal (HTA) bodies to make this available for patients as quickly as possible."

Ben Lucas, MSD Business Unit Director, Oncology

"2016 was a pivotal year. The critical thing for MSD was to ensure that immunotherapy, and the incredible scientific advances it represents, could become a medicine accessible to the British public. The big news for us had to be the advances in lung cancer treatment, particularly the data in the first-line lung NSCLC cancer setting. Looking back on what it really meant from the UK patients’ perspective, we managed to work successfully with the UK health system to progress the uptake of a new option in melanoma. We are very proud of what we achieved: building on our engagement through the Early Access to Medicines Scheme (EAMS) alongside the MHRA, NICE and NHSE. 2016 also brought challenges in access to cancer medicines. The cooperation with the system meant that we were able to get one of the fastest NICE approvals for melanoma, with EAMS enabling access from day one.

The great potential of immunotherapy is about redefining what it means to have advanced, incurable metastatic cancers. The hope for these medicines, that is being illustrated as the data matures, is that we not only see positive responses to the early stages of the disease, but we also see prolonged responses as we continue to explore what this means for survival.

The Cancer Drugs Fund (CDF) was meant to mitigate and correct the apparently lower performance of UK health services for cancer outcomes, and to a certain extent it did manage to achieve improvements. However, the future challenges to ensure affordability and deliver sustainable funding for cancer treatment may mean further uncertainty for patients in the short term around whether they will have access to innovative medicines. To continue making progress, all stakeholders in UK cancer treatment must continue to work in partnership.

We found it important to collaborate and engage early with our stakeholders. Our medicine was the first to achieve access through EAMS. This provided access for over 900 patients to Keytruda across melanoma and NSCLC, free of charge in a setting where data had already demonstrated the safety and efficacy profile but prior to full regulatory approval. Having now progressed beyond EAMS, we are now looking forward to a significant number of further regulatory applications to the FDA and the EMA across a number of indications in the coming 18-month period."

Of course, it is tempting to view the developing technologies as a ‘battle’ between three pharmaceutical giants and attempt to determine which will emerge as the winner; what is of critical importance is that the competition between the three, and the race for indications, actually indicates that more patients are being successfully treated with this exciting new form of therapy.  The expansion of treatment to a greater number of cancer sufferers will only benefit the field, and as MSD and Roche were keen to stress, further indications for 2017 are likely to come thick and fast. Over time, this could hold the most prominent significance for patients: that cancer may not be the death sentence that was once feared, even in those certain patients whose cancer has progressed to metastatic stage, as we now see they can show a strong reaction to immunotherapy. As further research is funnelled into the area, funded by increased sales, the prospect for the field only shows more promise; if the field continues to develop at such a rapid pace, it holds the potential to change the face of cancer treatment even more radically than it has in the last two years.