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Insider Interview: Allergan's R&D Chief on plans to be "the headache company"

Published on 22/02/18 at 10:46am

Speaking to Pharmafocus , David Nicholson, Chief R&D Officer at Allergan, revealed that the company has big plans in the migraine space to provide a relief to those patients who lose many days each month to the condition.

What’s Allergan’s background in the migraine area and how did this lead to being awarded the Enrico Greppi award for research?

The background for our interest is the fact that Botox is effective in chronic migraine and we also have some development compounds in the area in our pipeline. The award was about our involvement in the Cameo study, which was a longitudinal chronic migraine epidemiology and outcomes study.

It involved a huge number of migraine sufferers – some 17,000 – who suffered from chronic migraines (15 or more headache days a month) and episodic migraines (more than eight headache days a month). The study looked at the natural migraine disease course and at the impact of migraines on the ability of migraine sufferers to participate in society, as well as the impact on family lives and the economic impact. It was designed to provide an evidence-based foundation so that the impact of migraine treatment on all of those parameters could be quantified.

The results showed that, amongst many other things, migraine experience fluctuates in terms of the frequency of the headache attacks. It also showed that days alone are not sufficiently stable to differentiate between episodic and chronic.

What were the issues that were raised by patients that formed the study?

Patients revealed how living with migraines is truly debilitating – they have difficulty participating in society and it has massively detrimental impact on their family life as well. If we can start to offer improved therapies then clearly these individuals would be able to have a huge increase in the value of their daily lives. What we want to do is look for opportunities to collaborate with organisations and advocacy groups to get the word out about migraines, to encourage and empower folks suffering from this condition to talk to their health care providers to ask questions and seek answers for diagnosis and appropriate treatment options.

How will the results of the study be used?

The results of the study further inspired us at Allergan to continue to invest in the development of therapies for migraines – be it chronic migraine, episodic migraine or the treatment of acute migraine. Clearly we have Botox, which is approved for the treatment of chronic migraine. When I speak to the neurologists who treat patients or even the patients themselves, they all say how Botox really changes peoples’ lives.

Do such studies inform the targeting of particular difficulties of the condition in the clinic?

Patient centricity, and I know it’s a bit of a buzzword at the moment in the industry, but thinking about that not as a buzzword but as an idea that inspires us all to develop drugs across all of our therapeutic areas is really important to the people working at Allergan. What we want to do is develop drugs that truly benefit patients and meet an unmet need. That’s true in migraine, as it is in all of our therapeutic areas.

Studies like Cameo make it clear how big a need there is for new drugs. It also highlights the importance of reaching out to patients and asking them: “What are you looking for in a new treatment and what the symptoms that disrupt your daily life?” We can then incorporate measures in our clinical trials that are important for the patients. If a patient tells us one particular symptom is bothersome then we need to undertake measures to show that we are improving that particular symptom.

Beyond Botox, what else is Allergan working on?

We have in development Calcitonin gene-related peptide (CGRP) receptor antagonists – we are the leading company with orally active CGRP antagonists in late-stage development. We have one compound called ubrogepant that’s in late-stage development for acute treatment of migraine attacks; this is a drug that’s being investigated for use when people feel the migraine attack coming on. We also have atogepant, which has a slightly different profile from ubrogepant, and is being investigated for the prophylaxis of episodic migraine.

You mention that these are orally active; how does this differentiate you from potential rival treatments?

There are monocloncal antibodies against CGRP or against the receptor for CGRP, which are in development or finalised in development. There are actually four of these monoclonal antibodies which different companies are pursuing – these need to be given by injection, either subcutaneously or intravenously. History teaches us, across many therapeutic areas, that oral therapies are preferred over injectables. We are the first company to have these oral compounds in late-stage development. There are some other issues with monoclonal antibodies; when injected they are present in the body for weeks and there are some features associated with the continual presence of drugs in the body for prolonged periods of time. By comparison, oral therapy, which people prefer, can be more rapidly terminated if there is a reason to stop the therapy.

As for the treatments themselves, how are they progressing in the clinic?

Ubrogepant is in Phase 3 and we expect to get the results from our studies in the first half of next year, while atogepant is in Phase 2b; we also expected to receive the results from this study in the first half of next year.

CGRP inhibition has proven benefits in the treatment of migraines, and that’s based on the work of monoclonal antibodies, but also with these compounds and other related compounds tested in Phase 2 studies.

Novartis and Amgen recently released strong data from a Phase 3 study of their CGRP inhibitor – how promising are these breakthroughs for patients?

The Novartis/Amgen data, and other companies using monoclonal antibodies, and our data with small molecules, clearly demonstrate the CGRP inhibition is effective in treating migraines. I definitely think that there is a big unmet medical need for new mechanisms of action to control the symptoms of migraine.

Do you see Allergan cementing its positon in migraines with the potential approval of these drugs?

Absolutely. In this area, we would like to be viewed as ‘the headache company’. We mentioned how effective Botox is but, with the possible exception of antiviral agents, it’s very difficult to think of a therapeutic area where one mechanism of action effectively treats all symptoms in all patients. We, and other pharmaceutical companies, need to develop different mechanisms of action to complement one another to provide maximum benefits to patients.

This might mean monotherapy in some individuals, and some patients may react very well to treatment with just CGRP inhibitors, and in other patients there may be a partial response. However, there may be a greater response with the combination of Botox and a CGRP inhibitor.

How does the future look for migraine treatment?

There has been a hiatus in new treatment for migraines recently, particularly migraine prophylaxis where there has been a dearth, until Botox came on the market. People have tried using beta-blockers and antidepressants as off-label treatments, which do provide some benefits but only minor ones. With the arrival of CGRP inhibitors, this is the first time that a treatment has arrived that can treat acute migraines, as well as being used as prophylaxis. The next few years are going to be really exciting, as we’ll be able to use real world evidence for this new class of therapies for patients. This will generate data to determine how they can be best used together, with and alongside Botox.

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