Take ten years, half a billion dollars and countless man hours from some of the most highly trained, intelligent individuals on the globe. You still stand a 90% chance of failure, some of which is totally out of your control. This is the apparent reality of modern drug development.
With the odds so stacked against it, it’s little wonder that the drug development sector is one requiring constant evolution in rethinking how to survive. In addition to the ‘regular’ risks of drug development, turmoil in global markets since 2007 has seen risk adverse investors shun drug development and biotechnology stocks for blue chip companies which are perceived as safer. The pressure to perform has increased for those companies who continue to work in the space.
In short, it’s forced even greater creativity to ensure survival and prosperity.
Like many peer companies who have reached a late stage of drug development, Clinuvel’s path was unique and hardly comparable to other pharma companies. (Each company has its own challenges and they are seldom comparable to others within the same sector.) By 2006 SCENESSE® (afamelanotide), our lead drug, had captured the public’s imagination, but was only in its infancy from a regulatory perspective.
To reach the market, a new drug must be proven safe and effective in a specific medical ‘indication’ (you can read more about this process on the clinical trials section of our website). The drug product must also be manufactured to a certain standard, known in the industry as cGMP, or current Good Manufacturing Practice. These three criteria (safety, efficacy and quality) should be constantly under review by any development company in the knowledge that they are the yardsticks by which regulators will measure a program and, ultimately, determine whether a drug can be marketed.
For Clinuvel it became obvious that the mechanism of action of afamelanotide – activating melanin in skin – would best be suited for a number of specialities, dermatology, gastro-enterology and haematology. Less obvious in 2006 was whether the drug would prove safe and effective as a prophylactic or symptomatic treatment for the chosen indications.
Melanin has numerous properties within the skin, but one of our key understandings – and now fundamental to Clinuvel’s program – is its ability to protect skin from various wavelengths of light. Here, melanin acts as an umbrella over skin, reflecting and absorbing photons of light across the electromagnetic spectrum and preventing them from penetrating into the layers of skin where they can cause the most damage.
In all skin types, the penetration of invisible ultraviolet light (UV, particularly wavelengths of 280-400 nanometers) over time can cause damage. For fair skinned individuals in particular, excessive exposure of skin to UV over a period of time will lead to skin cancer.
It made sense for Clinuvel to pursue the potential for our drug to prevent skin cancer, but we needed to narrow the playing field to make drug development realistic and feasible for patients who needed the drug most. In ‘healthy’ individuals, skin cancer takes decades to develop. A trial program here would also take decades to develop (a Phase IIb alone would likely be 1,000s of patients over 10 years), so we focused on a subset of patients who we knew were more likely to incur skin cancer in a shorter period of time – immunosuppressed organ transplant recipient (OTR) patients. Even here, a multi-year chronic Phase II study is being conducted, so proving the drug may help safely prevent skin cancer is still some way off.
Delving deeper, the company learnt more about less common disorders which are caused when sun/light impacts upon skin. Many of these – known broadly as photodermatoses – are acute diseases: symptoms occur within seconds or minutes of sunlight exposure. Consulting and in dialogue with experts who lead the field of photodermatology, we identified a small number of these diseases and set about the rigorous task of clinical evaluation of the drug’s safety and efficacy.
Since 2006 it has become clear that one indication is the most promising for SCENESSE®: erythropoietic protoporphyria or EPP. Here, melanin is blocking visible wavelengths of light (particularly blue light), preventing them from penetrating the skin and causing the painful phototoxic reactions which are characteristic of EPP. In practical terms, we are seeing that the drug is safely enabling EPP’ers to venture outside in sunlight for the first time. For many it is literally life changing.
Regulatory support for the EPP program in the form of orphan drug designations, along with encouraging patient and clinical evidence of the drug’s effect, compelled the team to accelerate this program. It was evident from our conversations with external parties, and clinical trial results, that EPP was the indication with the best opportunity to prove SCENESSE® was a safe and effective treatment. More recent support from payors in Italy and Switzerland suggests that there is now a broader recognition of this opportunity to deliver a drug for EPP patients.
Our task is not over and there are still significant hurdles for the company to overcome. While now recognised in Europe, US and Japan, EPP has a lower profile on other parts of the world and the company is working to expand the understanding of this severe disorder. Vitiligo presents a new challenge – our first program dedicated to pigmentary disorders where the drug may be able to assist millions of patients is still in its infancy and will require further trials and fine tuning. The aforementioned OTR skin cancer program will also complete its first study this year, and may present us with a further avenue of development. It’s a fascinating time for us.
Drug development is full of uncertainty. One thing, however, is certain – the Clinuvel team will continue to evolve our program to maximise our chances of getting SCENESSE® to the patients who need it most.
“Medicine” posted to Flickr.com by Kevin (KB35) on October 19, 2007 <http://www.flickr.com/photos/kb35/1644550531/>