Man has been trying to characterise pain for centuries. A vortex of the spiritual, mystical and physical unravelling with a spectrum of distress, it is an enduring challenge.
The pursuit of pain relief is nowhere near over and many companies and institutions are chasing answers to reduce the impact of chronic pain and its corrosive byproducts: anxiety, fatigue, depression and fear.
The independent pharma company Grünenthal is keeping up the pace by building on its 42 business development and in-licensing deals of 2016 with a bullish start to 2017.
Gabriel Baertschi, who joined as CEO in October 2016 from AstraZeneca, is committed to R&D innovation and has pain in his sights on multiple fronts.
“The company is focused on expanding its leadership in pain and driving innovative therapeutic options in indications beyond pain, and there is a real commitment to that cause, which is very encouraging,” he says.
“I am impressed to see how much this company has done with its resources. It is a mid-size company, family owned, and it has been able to deliver innovation and put some important drugs on the market.
“There is an entrepreneurial spirit and I see a lot of people who are energised and willing to make a difference for the company. It has been a great start.”
His mission is to ‘turbo charge’ R&D and the company’s entrepreneurial growth, taking it from a €1.4bn company to a €2bn value while introducing four to five new medicines by 2022.
Disease patterns
At the core of Grünenthal’s work is a ‘pain landscape’, a research- and intelligence-driven map of almost 100 different pain indications, many with unmet need. It was drawn up by scientists and patients and will inform innovative routes to therapy.
“We have to see pain as a disease, not as a symptom, and as a worldwide leader in pain, we are not only committed to developing pain-relieving drugs but also to finding a better understanding of the disease patterns in order to explore disease-modifying approaches,” adds Baertschi, a biologist who has 20 years’ of industry experience and was AstraZeneca country president for Germany and then Japan, before joining Grünenthal.
The direction is in accord with the Societal Impact of Pain, the international platform to raise awareness and promote Europe-wide collaborations, which is calling for chronic pain to be recognised as a disease. With one in five European adults affected by chronic pain, that message will be echoed across the schedule at the European Pain Federation Congress in Copenhagen, in September 2017.
The need is clear. Seven of the top 50 searches on Patient.info are for pain. The site, one of the biggest patient information sources in the world with 250 million annual visitors, recorded 867,000 searches for pain information leaflets in January.
“It is mainly from patients but also from doctors who can be frustrated by what they can achieve for their patients,” says Dr Sarah Jarvis, the site’s clinical director. “Patients want a cure now and we cannot offer a cure, sometimes we cannot offer a temporary cure so patients with chronic pain tend to be less satisfied with treatment because it is difficult to find relief.
“There is some good work out there but the truth is we don’t understand enough about pain. We are trying but it is not easy.”
Baertschi believes the Grünenthal pipeline will provide answers.
Pole position
“The starting point for our work is the patient and their medical need,” he says. “Pain has been left aside a bit by big pharma and we are the only fully integrated R&D pharmaceutical company significantly investing in pain R&D right now. We particularly want to target smaller patient populations experiencing rarer syndromes or illnesses that may be less attractive or profitable for big pharmaceutical companies.
“In contrast to this, our strategy is to increase our core R&D investment from €170m in 2015 up to €400m annually in 2025.”
But Grünenthal has to contend with of one of its main revenue drivers, Palexia, going off-patent in 2025.
“We need to be prepared for this and we started this journey in 2016 by being quite aggressive with our business development and had more than 42 business development and in-licensing deals being made through the year and we already have a few deals lined up in 2017,” he says.
The acquisition of the US-based Thar Pharmaceuticals late in 2016 strengthened its ability in Complex Regional Pain Syndrome (CRPS), an orphan disease, and Baertschi adds: “Buying Thar and its lead compound against CRPS puts us in pole position in addressing this condition which has a high unmet need. Patients describe it as more painful than having an amputation or giving birth without training. In the US alone, there are 200,000 people suffering from it and we have the two lead components being developed for these patients – very exciting projects.
“We are involved in projects that go beyond pain – backed by our licence agreement with AstraZeneca for Zurampic in gout, a condition that causes joint pain flares and is diagnosed both by GPs and rheumatologists. It is a good fit strategically for us because it enriches our portfolio in the area of inflammatory and pain-related diseases with high unmet need.
“Pain has nervous and inflammatory components and we are interested in everything around the inflammatory process but also the central nervous system aspect of pain and adjunctive diseases such as rheumatoid arthritis and Parkinson’s. Understanding the neurons, the channels and signalling processes involved in pain is important, which is why we are involved in this space.”
Investment return
Its pipeline includes a clinical candidate compound which is a potential pain drug with a new mode of action; targeting the nociception (NOP) receptor as a peripherally acting agonist. It has the potential to reduce pain without typical opioid therapy side effects and is in development for topical application in hypersensitivity disorders such as Bladder Pain Syndrome or Chronic Stump Pain.
“The symptoms of Bladder Pain have a severe impact on patients’ daily lives,” adds Baertschi. “They experience a painful urge to urinate, some up to 50 times during day and night. Ultimately, many patients can’t go to work, leave their home or even have sex without pain. It is our passion to help these patients.”
It is also investing in New Technical Entities (NTEs) which include new formulations and devices, acquiring Zalviso, a combination of a medical device and pharma product, to treat post-operative pain, and an in-licensed innovative medical sealant for wound closure.
The other side of the investment coin is return and Baertschi believes that payer pressure is normal. “I understand the challenges they have of finding ways of curbing their overall healthcare spend,” he adds. “But I am convinced that every system is still trying to reward innovation and produce drugs that help address diseases with a high unmet medical need.
“Therefore, we are concentrating our efforts in areas of high unmet need where there is no solution. I’m not interested in me-too products or having the third-generation compound in a class. It is about driving higher value for patients with unmet need. CRPS is a good example as there is nothing there and we have two compounds in development.”
Passionate scientist
“I am a big believer that there will be a willingness to pay in those segments. It might not be as generous a recognition of the innovation as it was 20 years ago, but nevertheless it will be recognised.
“I’m a passionate scientist. I started in research and did my degree in biology, and innovation is close to my heart. That is why it is important for me to work in a company that is innovation-driven.”
The combination of R&D, business development and staying finely tuned to academic research and patient feedback will be the signposts for Grünenthal’s aim to be known as ‘the pain company’ and to gain an increased slice of the market that is worth $15bn worldwide.
“For a company of our size, this is an ambitious plan. We are going to turbo charge that delivery, not only through our own efforts but also with partners.
“My hope is that we succeed in getting these drugs to these patients. There is nothing more motivating than being part of a journey that shapes these products with our scientists and the rest of the team. It is very satisfactory when you talk to a CRPS patient who cannot take his children in his arms or cannot stand air conditioning, and we may be the company to offer the solution.
“That is very exciting; that is where the energy comes from. It is very challenging but it is also very inspiring.”