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Amgen bets on immunotherapy future

pharmafile | June 15, 2015 | Feature | Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing Amgen, immunotherapy, oncology, oncolytic, tom lillie 

When we speak to Tom Lillie he’s brimming with excitement about the future for Amgen in oncology and the future possibilities of new treatments for people with cancers.

Just days after Amgen’s oncolytic immunotherapy – T-VEC (talimogene laherparepvec) – hit the headlines, with noteworthy Phase III trial results in people with skin cancer, Lillie tells Pharmafile he feels that Amgen is set for big things in the field of immunotherapy.

T-VEC is an exciting technology. It was engineered by BioVex, which Amgen acquired in 2011. It’s a form of the herpes simplex or cold sore virus, which is engineered so it only replicates inside cancer cells, where it causes cancer cells to lyse – to split or pop – and release their internal contents.

That allows the immune system to ‘see’ the antigens and other foreign parts of the cancer cells; once exposed to the immune system it’s easier for the body to attack and destroy the cancer cells.

T-VEC is selective and only attacks cancer cells, and is also engineered to produce a molecule, called GM-CSF, which stimulates the immune system to attack and destroy the tumour. It is injected directly into tumour lesions in the skin and by releasing antigens from the tumour cells and stimulating the immune system, it allows the body to develop an immune response.

Amgen is the first company that is developing a virally-based cancer immunotherapy to publish mature – and positive – Phase III data. Other technologies with different viral vectors are at a far earlier stage in the development journey.

The recent OPTIM study, led by UK researchers at the Institute of Cancer Research in London, found it reduced the size of melanoma lesions on the skin where it was injected, but also more promisingly on other parts of the skin.

“What we saw in the OPTIM study that was most exciting was it clearly had an impact in the cancer cells where it was injected, but it also affected melanoma lesions elsewhere in the body where they weren’t rejected,” Lillie says.

“So the body’s immune system must have picked up the antigens and was making its own response. It’s the first trial that has shown a viral therapy like this can be used to treat a cancer effectively and that’s really exciting and nobody has shown before that it – oncolytic immunotherapy – can work before.”

The study of 436 patients with skin cancer found 16.3% of people given T-VEC showed a durable treatment response of more than six months, compared with 2.1% of those given a control treatment.

Although median overall survival just missed the benchmark for statistical significance (the 4.4 month different in overall survival was ‘tantalisingly close’ as Lillie puts it) some patients had a response extending past three years – a mark oncologists often use as a proxy for cure in immunotherapy. It was published in the Journal of Clinical Oncology.

People in the study who had not previously had any treatment and those with early-stage melanoma showed the best response to treatment with the drug – prompting experts and investigators to speculate whether T-VEC could or should hit the market with a first-line indication.

This is something Lillie says Amgen is likely to pursue in the future. “It takes time for the immune response to build and impact the tumour; so starting earlier when people have time to make a response and getting to the disease when there’s less cancer for the immune system to tackle I think does make a lot of sense. For a potential first-line treatment it has quite manageable side effects and that’s another reason why earlier use could be quite interesting.”

And as Lillie explains, T-VEC’s potential could extend beyond melanoma – for which an FDA panel recommended it as a potential treatment in April, although the final decision is down to the FDA.

“We’re focussed on our current regulatory submissions so making T-VEC available to melanoma patients is where our priority lies for now,” Lillie says. “But we’re certainly looking in other tumour types like head and neck cancer as well as melanoma, and we’re considering use at earlier times as well. There are a few studies that will look at its use in earlier-stage patients and we think that has a lot of promise.”

These studies include a Phase Ib/II study of T-VEC as a first-line treatment for patients with later-stage melanoma that has spread other parts of the body. Amgen is also running trials which – if successful – could spur the company to pursue other licences in the future.

During the American Society of Clinical Oncology (ASCO) conference Amgen announced a collaboration with Merck, manufacturers of Keytruda (pembrolizumab), to evaluate the efficacy and safety of T-VEC in combination with Keytruda.

The two firms will start a Phase I trial of patients with recurrent or metastatic squamous cell carcinoma of the head and neck cancer.  They will also partner on a global Phase III trial evaluating the combination in patients with regionally or distantly metastatic melanoma.

“T-VEC and Keytruda are designed to result in anti-tumour immune responses through different and potentially complementary mechanisms of action. “We believe that T-VEC has potential in several cancer types,” Sean Harper, Amgen’s executive vice president of R&D says. “We hope these trials will provide us with insights on the combination of these therapies for patients with this form of cancer.”

The companies say the collaboration could exploit the two treatment’s effects on the immune system: using T-VEC to press the accelerator of the body’s immune system, while Keytruda takes the brakes off the immune system at the same time.

Lillie says: “We’re very excited about the ability to combine with other immunotherapies. We’ve already published some early combination data in a very small number of patients that were very encouraging. We saw a marked increase in response rates by combining it with Keytruda and Yervoy. There’s a lot of oncology expertise in both companies so it’s always good to share expertise; in designing trials and bringing new treatments to patients.”

Like other companies Amgen used the ASCO conference as a vehicle to showcase what can be interpreted as their oncology strategy for the coming years.

In multiple myeloma Amgen unveiled new data looking at Kyprolis (carfilzomib), in a Phase I and Phase II study of patients with relapsed or refractory forms of the disease.

In the Phase II portion of the study in 89 patients, the percentage of patients achieving a partial response or better was 72% – while 80% of people showed at least the minimal clinical response. Based on the results from this Phase I/II CHAMPION trial, Amgen initiated the Phase III ARROW trial evaluating the benefit of Kyprolis administered once-weekly.

In another promising move in the immunotherapy area, acute lymphocytic leukaemia treatment blinatumomab (AMG103), which is marketed in the US and under review by the EMA, has demonstrated ‘really exciting efficacy’ in early trials, Lillie says.

“We’re bringing a new technology to meet a very unmet need in this group of patients. Acute lymphocytic leukaemia is like melanoma; a couple a years ago there were very few treatments and a desperate situation for patients, and now there’s been an explosion of new treatments, lots of choices and lots of improvement in outcomes.”

Many of the post-ASCO headlines were grabbed by studies with dramatic results of immunotherapy treatments, in particular for Bristol-Myers Squibb’s immunotherapy treatments Opdivo (nivolumab) and its combinations with Yervoy (ipilumumab), and Pfizer’s breast cancer drug Ibrance (palbociclib).

And there is a real sense that immunotherapies like these, and oncolytic immunotherpaies such as T-VEC, are going to bring a real shift in the landscape of cancer treatments – if their cost does not prove a prohibitive barrier to access.

Lillie expects Amgen to be among the main players in this new area, combining its treatments with others that have made recent news. “Amgen has a long-standing commitment in oncology so of course we’re always excited to be at the forefront of this area and a new technology.

“It’s very important to us to be innovative and to bring novel and effective therapies to patients. Immunotherapy is probably one of the hottest things that’s going on in oncology at the moment. The studies comparing and looking at different ways of using these therapies, and targeted therapies, means there are lots of approaches and potential ways of offering patients better outcomes.”

Lilian Anekwe


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