For millions of people living with rare diseases, there are very limited options in the treatment regime. Many of these diseases affect relatively small patient populations, making new medications difficult to develop for pharmaceutical companies. As a result, these illnesses are referred to as orphan diseases, and drugs and vaccines developed for them are known as orphan drugs.
Despite these obstacles, medical research, government incentives and the efforts of innovative biotechnology companies are opening up new opportunities for patients who once had little hope. One example is the development of Atiprimod, an investigational therapy that’s being studied for treatment of multiple myeloma (a rare and often life threatening blood cancer).
Understanding Multiple Myeloma
Multiple myeloma is a cancer that develops in plasma cells, a type of white blood cell that is present in the bone marrow. As abnormal plasma cells multiply, they crowd out healthy blood cells and can weaken bones, damage kidneys, and impair the immune system.
Common symptoms may include:
- Persistent bone pain
- Frequent fractures
- Fatigue
- Anemia
- Recurrent infections
- Kidney problems
While great progress has been made, multiple myeloma is still a disease that remains incurable for many patients and so continuing research is urgent.
A Personal Reminder of the Need for New Treatments
The importance of developing better treatments became particularly personal for Gary Jacob, Chief Executive Officer of Callisto Pharmaceuticals, Inc.Jacob learned about one of his doctor's close friends who had suffered what appeared to be a simple accident while playing with his child. When he broke a rib, hospital examinations would quickly reveal that he had multiple myeloma.Jacob’s story made clear that there is a pressing need for more treatment."Everyone agrees we need more drugs to treat multiple myeloma. There are people out there dying without real hope because of a lack of effective treatment," Jacob said.
What are Orphan Diseases?
Orphan diseases are conditions that affect relatively small numbers of people.In the United States, the Food and Drug Administration (FDA) defines an orphan disease as one affecting fewer than 200,000 individuals.Although each rare disease affects only a very few people, they affect millions.According to the National Organization for Rare Disorders (NORD):Almost 25 million Americans live with one of about 6,000 rare diseases.
Examples include:
- Multiple myeloma
- Cystic fibrosis
- Gaucher disease
- Hemophilia
- Huntington's disease
- Amyotrophic lateral sclerosis (ALS)
- Some rare cancers
Some rare diseases affect only a few hundred (or even fewer than one hundred) patients worldwide.
The FDA Orphan Drug Program
Prior to the Orphan Drug Act of 1983, very few treatments were developed specifically for rare diseases.In the decade before the legislation, only about 10 orphan drugs reached patients.The FDA has approved hundreds of orphan drugs since the Act was adopted, while many more are under investigation.
The program incentivizes research by providing incentives such as:
- Research grants
- Tax credits
- Seven years of marketing exclusivity after approval
- Regulatory support during development
These incentives encourage small biotechnology companies to invest in treatments that they might never have in their patients’ hands, however.
Small Biotechnology Companies' Role
Because rare diseases affect relatively small populations, many large pharmaceutical companies have historically invested less in orphan drug development.According to FDA officials, only a small percentage of orphan drug applications have traditionally come from major pharmaceutical manufacturers.
Instead, smaller biotechnology companies have dominated innovation in this field and taken on much higher financial risk for patients with few options.
Atiprimod: A Promising Investigational Therapy
One investigational drug to receive orphan drug designation is Atiprimod, which is being developed by Callisto Pharmaceuticals.The company received FDA orphan drug designation to support its continued clinical development for multiple myeloma.Atiprimod has been studied to determine what is involved with cancer progression because of a number of biological processes.
Early laboratory research suggested that the compound may:
- Inhibit the growth of some cancer cells
- Promote programmed cancer cell death (apoptosis)
- Reduce the formation of new blood vessels that tumors require to grow
These results needed to be further evaluated through clinical trials.Clinical DevelopmentCallisto announced the initiation of Phase I/IIa clinical trials to evaluate Atiprimod in patients with multiple myeloma.
Early-phase clinical trials are primarily designed to assess:
- Safety
- Appropriate dosing
- Side effects
- Preliminary evidence of effectiveness
Because these studies involve relatively small numbers of participants, such larger clinical trials are necessary before a treatment is safe and effective enough for regulatory approval.
Expert Support for Continued Research
Among those supporting further investigation were Dr. Kenneth C. Anderson, Director of the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School.Dr. Anderson was instrumental in the development of Velcade (bortezomib), one of the major treatment advances for multiple myeloma.Even after treatments such as Velcade have been proven to improve patient outcomes, many patients will require additional treatment for disease progression or treatment resistance.Such a need continues to drive research into new therapies like Atiprimod.
Progress in Rare Disease Research
Research of rare diseases has soared in the last few decades.
Genetics, immunotherapy, molecular biology and precision medicine have improved scientists' knowledge of many previously untreatable disorders.In light of the current state of medicine, patients with rare diseases have access to a lot more treatment options now than they had even a generation ago.While there are still many orphan diseases in which medicines are not effective, the pipeline of investigational drugs continues to expand.
Orphan drugs are one of the most important advances we are making in modern medicine for patients living with rare diseases. The government incentives, scientific innovation, and the dedication of researchers have transformed the view of diseases once considered untreatable.Although investigational therapies like Atiprimod need to be thoroughly tested in clinical trials before their safety and effectiveness can be established, there is hope for patients with diseases like multiple myeloma.With developments in biotechnology, the future of orphan drug development could bring new treatments and new hope to millions of people living with rare diseases around the world.
