Spotlight – March 2015

View PDF

Niche-Disease: Fanconi Anemia

by Cheryl Scott

Fanconi anemia (FA) is a rare, genetic blood disorder that causes bone-marrow failure. It prevents bone marrow from producing sufficient new blood cells and/or makes it produce faulty blood cells. Although FA is a blood disorder, it can affect many organs, tissues, and systems. Children who inherit the condition are at higher risk of being born with birth defects. It is a complex and chronic disorder that can be psychologically demanding. FA is not Fanconi syndrome, another rare and serious condition (of the renal system instead) that is mostly found in children. Both disorders were named for Swiss pediatrician Guido Fanconi, who first identified them in the first half of the 20th century.

FA strikes about one in 350,000 people worldwide. It results from a genetic defect in a protein cluster responsible for DNA repair. Thus, most FA patients develop cancer as well as bone-marrow failure by age 40. Common congenital defects associated with FA include short stature; abnormalities of the skin, arms, head, eyes, kidneys, and ears; and developmental disabilities. Three out of four FA patients manifest an endocrine problem, and their median life expectancy is 30 years.

Treatment with androgens and hematopoietic growth factors temporarily helps 50–75% of patients with bone-marrow failure, but bone-marrow transplants are currently the only long-term treatment. Because of the genetic DNA-repair defect, FA patients are sensitive to drugs that treat cancer through DNA crosslinking (e.g., mitomycin C). Early clinical gene therapy trials are ongoing, involving organizations such as the US National Heart, Lung, and Blood Institute at the National Institutes of Health and companies such as Discovery Genomics, Inc. of Minneapolis, MN. And generation of patient-specific induced pluripotent stem has shown promising results. Meanwhile, some small-molecule interventions have delayed tumor onset (1).

The Fanconi Anemia Research Fund (FARF, http:// was founded by Lynn and Dave Frohnmayer in 1989 with a stated goal of finding effective treatments and a cure for FA as well as to provide education and support services to affected families. The Frohnmayers lost two daughters to complications of the disease. Their father was a prominent Republican state-level politician in Oregon and president of the University of Oregon, which provided FA and the organization with some visibility. He was also founding director of the National Marrow Donor Program and served as a member of the Fred Hutchinson Cancer Research Center’s board of trustees.

The FARF has sponsored 183 research grants in 54 laboratories worldwide. No FA genes had been identified when the fund began operation in 1989; 16 genes have been discovered. And bone-marrow transplant success rates for FA patients with matched unrelated donors have risen from 0% in 1989 to >87% today in transplant centers that specialize in Fanconi anemia. Matched sibling donor transplants have risen from a 35% success rate to close to 100% today in those centers. For interested researchers, the FARF’s 27th annual symposium will be held in Toronto, ON, Canada this September.

1 Shukla P, Ghosh K, Vundinti BR. Current and Emerging Therapeutic Strategies for Fanconi Anemia. The HUGO Journal 6(1) 2012;


A Pain MAb for Dogs (and Cats)?

In December 2014, Australian veterinary biopharmaceutical company Nexvet announced a distribution agreement with Irish animal health company Virbac for monoclonal antibody (MAb) treatments in companion animals. This deal covers the species-specific MAb product NV-01, which is currently in development for treatment of osteoarthritic pain in dogs, which Virbac will market outside the United States and Canada.

Nexvet’s proprietary PETization platform is designed to rapidly create MAbs that will be recognized as native/self by an animal’s immune system, affording them “100% species specificity.” Building on safety and efficacy data from clinically tested human therapies, the company can reduce clinical risk and development costs. Its first product candidates are antinerve growth factor MAbs for controlling osteoarthritic pain in dogs (NV-01) and cats (NV-02). The company expects data from a pivotal safety and efficacy study for the former by the end of 2015 and for the latter in 2016. The third product candidate will be a fusion tumor necrosis factor (TNF) inhibitor protein for treating chronic inflammatory diseases (e.g., atopic dermatitis) in dogs.

Nexvet staff have experience in development of both human biologics and veterinary drugs. For example, CEO Mark Heffernan was formerly with Opsona Therapeutics. “Virbac is an established leader in the companion animal health space,” he says, “with expertise in navigating the differentiated regulatory and commercial environments within European and other international markets, which together represent over 50% of the global market for companion animal health. This partnership is a strategic milestone, securing NV-01’s commercial launch in key international markets by accessing Virbac’s proven expertise and networks.”

“We are impressed with the Nexvet platform technology,” commented Virbac executive board member Christian Karst, “and its ability to rapidly create a unique and differentiated portfolio of biological products. NV-01 is unlike any other product on the market or in clinical development for chronic canine pain.”


Toward a Cure for Paralysis

The Conquer Paralysis Now (CPN) Challenge program will award nearly US$20 million dollars in grants and prizes over the next decade, including a tentative $3 million in business and entrepreneurial awards. The first team that can reach unprecedented improvement in everyday functions of people living with chronic spinal- cord injury will win a $10 million grand prize.

CPN ( is a foundation started by former Indy Racing League driver Sam Schmidt, who is quadriplegic due to a racecar accident in 2000. “We’ve done a lot of great things with the foundation in the past 14 years,” he said, “but there are millions of people like me who are still in their chairs, and it’s time to change that.”

Ida Cahill is CPN’s president and CEO. Announcing the contest at the World Stem Cell Summit in San Antonio, TX, she said, “We will find a cure for paralysis within the next decade, if not sooner. We have a plan and the commitment to make this happen. Through innovative funding and collaboration, we will drive research to help others be able to hug their children and loved ones once again.”

The CPN Challenge will provide a centralized research platform for scientists to share both their successes and failures. Open sharing lowers the risk of duplicating unsuccessful efforts and should drive progress to a cure even faster.


R&D Spending Leaders

London, UK, research and consulting firm GlobalData reports that the world’s top 30 pharmaceutical companies spent a combined $112 billion on research and development (R&D) in 2013. That represented an increase of $723 million over 2012. GlobalData’s December 2014 report identifies Roche as the R&D spending leader (outlaying nearly $10 billion). Novartis and Johnson & Johnson increased their spending the most, with each adding around $500 million. Novartis’ R&D spending grew by 5.6% to $9.8 billion, and J&J spent $8.2 billion, which was up by 6.8% from 2012.

Industry analyst Adam Dion says that these increases are partly attributable to pipeline programs advancing into costly later-stage clinical trials. “Roche’s R&D spending was bolstered by continued investments in its oncology and neuroscience therapeutic areas (such as the company’s investigational anti-PD-L1 antibody targeting lung cancer) and advancement of its programs for Alzheimer’s disease. Novartis’ R&D spending grew largely because its Alcon subsidiary allocated additional resources to develop new eye-care products. The company’s vaccine and diagnostics products business invested heavily to bring to market its meningitis B vaccine.”

Despite the overall increase in R&D spending, some large companies pulled back on clinical investment in 2013. “In efforts to improve profit margins, cost-cutting still remains a strategic necessity for some players. Many companies reduced their work forces to help stabilize profits in the aftermath of patent losses.” For example, Pfizer cut >$1.2 billion of R&D spending after losing market exclusivity on two major products. Merck continued a multiyear restructuring program by cutting >$600 million from clinical operations in 2013.


Third “Pharma Integrates” Conference

At the Park Plaza Riverbank in London, UK, on 18–19 November 2014, the third “Pharma Integrates” conference brought together more than 200 participants to discuss the state of the pharmaceutical industry and key issues it faces. The meeting is presented by Life Sciences Index of Surrey, UK.

In opening this event, David Brennan (retired CEO of AstraZeneca) remarked, “The pharmaceutical industry has had an incredible impact in improving and extending the lives of innumerable people for many decades. Current therapies, both on the market and in research, will no doubt continue to contribute to that incredible influence and have an even greater effect on the lives of millions all around the world.”

With an overarching theme of strategically transforming pharmaceutical relationships, speakers and participants debated what the future will look like and how to get there. Three themes emerged: integration, innovation, and a focus on individuals. Hot topics included strategic partnering, staffing and outsourcing, patient advocacy, generics, and use of mobile devices in healthcare. Discussions covered market trends and opportunities, a paradigm shift from batch to continuous processing, and disruptive technologies in the future of drug manufacturing.

Trevor Jones of Allergan described the conference as covering “the challenges and opportunities for partnership and collaboration facing the pharmaceutical industry in a rapidly changing environment. Participants engaged in productive discussions regarding the need to embrace disruptive technologies and new players to drive future successes — especially the increasing involvement of patients, medical technology, and large data sets in drug discovery, development, and commercialization.”