A new metastatic melanoma product, ipilimumab (sold as Yervoy), from Bristol-Myers Squibb (BMS), has the potential to be a blockbuster. Malignant melanoma is increasing in frequency and this is the first new drug approved for the condition since 1998. Unlike previous treatments, it has been shown to increase life expectancy in patients by several months on average, and 28% are alive after two years, compared with just 14% using the previous treatment. Rather than the story of a single innovation, ipilimumab’s development shows how co-operation can yield a
 eries of innovations that are sometimes needed to create a new drug.

To begin with, the drug itself has a novel approach. Rather than target the disease directly, ipilimumab is a monoclonal antibody that disables certain proteins that inhibit the body’s own immune system. In essence, it turns off the biological safeguards that prevent healthy people from developing autoimmune conditions. The immune system can then attack tumours much more aggressively. The big potential drawback is that this can leave patients open to a variety of other diseases. On the positive side, although ipilimumab has not been tested on other cancers, in theory it might work on some of these as well.

As with many biotechnology products, ipilimumab was not developed by a single company but relied on co-operation with academia and other companies. The original idea came from discoveries at the University of California at Berkeley in the late 1990s, which initially were too unusual to arouse major corporate interest. They were eventually taken further by Medarex, a biotechnology company. In 2004, Medarex and BMS agreed to partner on the drug’s further development and testing. This relationship proved so valuable that BMS acquired Medarex in 2009.

This was not simply a story of a large company buying up a promising compound. In addition to providing substantial financial resources and the manufacturing and marketing experience that its partner lacked, BMS brought extensive knowledge of oncology and drug testing. For Brian Daniels, senior vice-president for global development and medical affairs at BMS, internal R&D strength is essential to effective collaboration in drug innovation. “You need to be able to ask if the molecule you are looking at externally has the potential,” he says. “To answer that question,  ou need a large number of internal experts who understand drug discovery and development.”

Further innovation proved necessary at the testing stage. Cancer immunotherapy is a relatively novel field and previous methods for evaluating oncology products were based on chemotherapy. But these did not fully address the new approach’s biology and mechanisms, so BMS partnered with “key thought leaders to really advance the understanding of the relevant scientific endpoints,” Dr Daniels says. This also created a more appropriate testing framework that can be applied to new immunotherapy trials. This involved cooperation with a number of leading research charities, international bodies and clinicians.

Finally, says Dr Daniels, BMS has customised its customer relations processes to address some of the issues relevant to the drug. These include its novelty, high price (the four-injection treatment costs US$120,000) and side effects. “As soon as an order is placed,” he says, “a variety of people—a reimbursement specialist, a melanoma sales specialist, and medical specialists—are made aware in order to give the patient important information about access and safe use. It is a real innovation in our customer model in a very specialised area.” He adds
that, although the model itself does not address the price, it seeks to make doctors and patients aware of BMS programmes for the uninsured and underinsured.

What BMS’s experience highlights is that a single innovation is rarely enough for a big breakthrough. Instead, firms need to be prepared
to innovate and co-operate in a variety of areas.