The approval of novel orphan drug designations continues to grow, while many existing rare disease therapies are receiving approval for expanded indications. With this increase and broadening class of products, including some that target the same mutation or molecular defect, sponsors face new and significant market access challenges in securing reimbursement.
Leading manufacturers increasingly employ stakeholder research early in development to better identify the needs of patients and providers. This strategy can build in compelling asset value during development, help avoid pitfalls and better inform go/no-go decisions earlier to avoid costly development delays or even dead-ends. Continue reading
Non-alcoholic steatohepatitis (NASH) can lead to serious conditions such as cirrhosis and its complications, liver cancer and hepatic transplantation. Many patients eventually die from liver-related problems or cardiovascular disease. The challenge in developing drugs for NASH is to demonstrate an improvement in clinical outcomes. Cirrhosis takes several years to develop, and it is impractical to perform such long studies to identify treatment benefits. Therefore, to expedite the process and deliver new drugs to patients, biopharmaceutical companies have to consider surrogate endpoints that are reliable, can be obtained within a reasonable amount of time and are associated with progression of the disease.
A range of liver-related outcomes
NASH patients face many potential disorders and complications. In addition to overall death and liver-related mortality, the following endpoints should be evaluated in a clinical outcomes study:
- Portal hypertension. Chronic injury to the liver results in a wounding response that leads to fibrosis, scarring and ultimately replacement of normal liver architecture with regenerative nodules. As a result of these changes, portal hypertension develops.
- The accumulation of fluid in the abdomen results from portal hypertension. Using diuretics and reducing sodium intake often helps, but some cases are difficult to treat.
Novel biomarkers represent a promising means to improve diagnosis of nonalcoholic steatohepatitis (NASH). Currently, a definitive diagnosis requires a liver biopsy, a surgical procedure with many limitations. There are a variety of biomarkers that can assess liver status, but they do not always distinguish between patients with NASH and those with other disorders. Advanced imaging techniques, while useful for evaluating some liver features, can be impractical and costly.
The ultimate goal is to find noninvasive biomarkers that clearly show if the patient has steatohepatitis or liver fibrosis associated with nonalcoholic fatty liver disease (NAFLD). Recent studies suggest that nuclear magnetic resonance (NMR) spectroscopy, microRNA tests and genotyping may prove to be useful tools. Incorporating additional biomarkers into clinical trials can give biopharmaceutical companies an early indication of whether a compound is efficacious — and provide the confidence to move forward to the next phase of clinical testing. Continue reading
Our industry is witnessing increasing growth in the rare disease market, thanks to financial and regulatory incentives to develop orphan drugs. This has been good news for both sponsors and patients, but the fact remains that rare disease trials are inherently challenging to run. In addition, completing a complex study and reaching regulatory approval does not necessarily translate to market success.
John D. McDermott, Jr., Vice President of Covance Market Access Services, recently shared his insights on the market access challenges in rare disease drug development and discussed key considerations for sponsors and stakeholders.
Provide early education about the disease
Even though rare diseases as a whole are getting more attention, sponsors cannot assume that their potential payers know much about the particular condition they are targeting and its importance to patients. Continue reading
The pre-clinical phase of development for non-alcoholic steatohepatitis (NASH) drugs faces many challenges. Biopharmaceutical companies have several options for rodent models, but they must weigh factors such as customization versus speed before deciding on the best approach.
Some of the challenges include:
- Diet: There is no prevailing wisdom in the field suggesting that one induction diet is superior to another.
- Duration of disease induction: Depending on the type of diet, it will take 6 to 9 months for models to exhibit NASH-like features.
- Translation: Novel biomarkers used in human clinical trials need further validation in rodent models.
Is it possible to get more efficiency in your conventional and specialty tests while maintaining ongoing quality? ISO 15189:2012 accreditation answers this question by delivering a comprehensive approach to quality management in medical, central and referral laboratories. Not only can these standards ensure quality, but they can reduce your risk of costly delays and ultimately save money in your trials.
“It’s no surprise that sponsors are concerned about the risk of regulatory findings and increasingly requesting ISO-accredited labs,” said Paul Kirchgraber, Vice President and Global General Manager at Covance Central Laboratory Services. “They need a demonstration of increasing quality—and savings—across their outsource vendors. Adopting ISO 15189:2012 is a powerful way to highlight our broad quality standards that meet or exceed their expectations.”
Like my colleagues at Covance, my work ultimately contributes to improving healthcare and patients’ lives. Our efforts to accelerate fresh approaches towards effective treatments became deeply personal in 2007 when my oldest sister, Vicki, was diagnosed with advanced Triple Negative Breast Cancer (TNBC).
From her initial diagnosis, my sister was full of vitality and enjoyed a high quality of life due in part to several of the novel treatments that Covance had helped develop. She even participated in a long-term clinical trial involving an angiogenesis-inhibitor, in addition to traditional chemotherapy, during her early treatment.
Vicki became a student of her diagnosis, reading countless journal articles on the rapid advances in scientific understanding. When her health took a sharp decline, she asked for my support in helping her gain access to a new trial focused on the immune system. She wanted to do whatever she could to help others find a better treatment, or even a cure, for TNBC. Ultimately, she was too weak to make the journey to participate in a cutting-edge clinical trial. Vicki died on October 1st, 2013.
Change is in the Air
There’s reason for new hope in the ongoing battle against cancer. From standing-room-only presentations of provocative data at cancer conferences, to landmark publications and new drugs approvals, the signs are multiple and clear. Harnessing the immune system as an anti-cancer therapy–a strategy that has yet to fully deliver on its promise– is now the most exciting area of oncology drug development.
Immune Surveillance: an Invisible Malignancy Sentinel
The first chapter in the story of cancer immunotherapy is a tale that provides perspective on how evolving scientific insight serves as a backdrop to the interplay between human hopes and the sometimes capricious nature of medical advances. But that story is well beyond the scope of the next 800 or so words. However, we can take advantage of hindsight to consider some of the key lessons learned. Continue reading
Good news for the Duchenne Muscular Dystrophy (DMD) community. On June 8th, BioMarin announced the filing of a Marketing Authorization Application to the European Medicines Agency for Drisapersen, an antisense-mediated exon 51-skipping compound able to target the most prevalent genetic mutations responsible for the lack of production of functional dystrophin. The European filing follows the submission of a New Drug Application to the US FDA for Drisapersen back in April 2015.
Normally, dystrophin bridges cytoskeletal proteins to extracellular matrix and stabilises muscle fibres during contraction. The lack of its production in DMD leads to muscle damage, progressive muscle wasting, severe disability and premature death between the second and third decades due to cardiac or respiratory failure.
Iteration is the key for earlier and better decisions
The great inventor Thomas Edison once said, “I have not failed. I’ve just found 10,000 ways that won’t work.” While he was not talking about compounds, he could have been. The likelihood of success for any given compound is less than one percent. Aggravating the situation are several other factors, including constant pressure on decreasing pricing, quickly diminishing point of return at the 20-year mark, and along the way, inherent risk and large investments.
Still, we persevere. But to be successful in today’s environment requires a different, non-linear approach. The status quo will not work. We recommend taking a holistic view of the drug development process and an integrated approach. Continue reading