Rare Disease Parent Meets with President Trump

By: James Radke

Source: Rare Disease Report

On Monday March 13th, rare disease parent Stan Summers of Box Elder County, Utah talked with President Trump about the struggles that many rare disease families face with regard to medical insurance. He talked about his frustration in dealing with the high deductible payments and the need for multiple jobs in order to care for his son who has a rare, chronic disease (IGg4 Systemic Sclerosing Disease). 
 

Summers' remarks were part of a listening session about healthcare hosted by President Donald Trump and Vice-President Mike Pence. Stan Summers’ son, Talen, has IGg4 systemic sclerosing disease which is a systemic fibro-inflammatory disorder. Talen was a healthy young man until his mid-teens when the symptoms began to appear. Years of pain and countless doctor visits finally led to a correct diagnosis when he was 23. Now 26-years-old, his muscles continue to harden around his organs and he is in constant pain but as his blog post notes, he will never give up.

The full video can be viewed here: http://www.raredr.com/news/rare-parent-trump
 

The FDA’s Rare Diseases Program: Driving the development of orphan drugs

Written By: Dr. Nicola Davies

Source: thepharmaletter

Rare diseases are characterized by the US Food and Drug Administration (FDA) as those conditions that affect less than 200,000 people in the American population. While 200,000 may seem a large number, it is obviously characteristic of rare diseases to be…well, rare, says Dr Nicola Davies in her regular exclusive contribution to The Pharma Letter.

For example, Cushing syndrome - an endocrine disorder that affects adults 20-50 years of age, has a prevalence rate of 5.9 for every 100,000 people. This small statistic of incidence is just one of the hurdles that pharma companies must face in the development of orphan drugs. Orphan drugs are expensive to develop, design, and market - while providing a low rate of return - making these drugs expensive to produce and distribute. This not only means that the development of orphan drugs can be unattractive to companies, but it also makes access to orphan drugs difficult and expensive for patients who need them the most.

To combat the unavailability of drugs for rare diseases and to encourage the development of orphan drugs, the Center for Drug Evaluation and Research (CDER) - a branch of the FDA - initiated the Rare Diseases Program to work with industry partners to develop orphan drugs.

What does the Rare Diseases Program offer?

The development of orphan drugs faces several challenges. For one, the prevalence of some rare diseases results in a historically low number of data points to determine the disease’s natural history and pathophysiology. Data availability is even lower for rare pediatric conditions. Those who develop orphan drugs, therefore, have to rely on historical or even anecdotal data to develop drugs. This results in increased costs and manpower invested in drugs to be used by very few. In addition, small data sets result in prolonged duration of drug development. This can be detrimental in rare diseases with poor prognosis and a progressive nature.

One of the outcomes to emerge from the recognition of these challenges in orphan drug development is the initiation of the Rare Diseases Program. Despite rare diseases affecting miniscule portions of the population, the FDA still considers them a public health issue and strongly encourages the development of drugs for rare diseases. It supports these efforts by exempting developers from user fees, providing marketing exclusivity on the drug (marketing rights protected by law), and grant supports for drug development. In addition, other branches of government offer tax credits and other incentives.

Due to the many challenges that orphan drug development faces, the FDA has relaxed some of its strict guidelines to encourage development of cures for rare diseases. For example, there are some toxicology study exceptions for orphan drugs that do not exist for common diseases. To this end, the Rare Diseases Program encourages pre-Investigational New Drug (pre-IND) application meetings to discuss rare disease exceptions and facilitate information exchange. In addition, orphan drugs are often eligible for accelerated approval that allows them to be approved with early signs of clinical benefit. Orphan drugs can also qualify for fast track status that allows pharma companies to essentially apply for new drug status so that the drug can be monitored on a rolling review basis as and when trials are completed. 

Has the Program made a difference?

Since 2000, the number of orphan drugs is on the rise. As many as 165 drugs were designated as orphan drugs in 2008 compared to only 69 in 2000. Of these drugs, oncology drugs accounted for about one third of approved orphan drugs between 2000 and 2006. Hematologic conditions and immunologic disorders also saw a near 10% drug approval rate among orphan drugs. These numbers generally indicate that CDER policies on orphan drugs are having a positive impact on the pharma industry. Indeed, the Rare Diseases Program has largely encouraged investment in orphan drug development and is growing to become a valuable resource for the pharma industry.

However, there has also been some criticism of the program. There have been claims that in orphan drug applications, there is considerable reviewer variability and varying degrees of flexibility with approved study designs. In addition, the CDER itself has initiated discussions on the lack of resources it faces and the resulting lack of pre-application meetings and follow-up on agency funded studies. 

The Healthcare Professional’s perspective

Orphan drugs largely improve longevity and quality of life in those living with rare conditions, particularly rare pediatric conditions. In addition, the Rare Diseases Program may also be viewed by physicians as a resource for more information on conditions they don’t encounter regularly. Physicians are now able to offer treatments and alternative treatments to patients with rare conditions. This is largely because of the FDA’s consolidated list of approved orphan drugs. This widely available information enables doctors and other healthcare professionals to point patients in the direction of subsidies for expensive medications.

While health professionals seem to applaud the strides the pharma industry has made in terms of orphan drugs, price remains an issue for them.1 Orphan drug treatments are expensive and may remain out of reach to those who cannot afford it. Despite the high costs, though, the program has provided many incentives for developers to invest in orphan drugs. This is particularly true of pediatric rare diseases, through the priority review voucher (PRV) program, which has supported the development of drugs like elosulfase alfa (Vimizim) for Morquio A Syndrome. In addition, health professionals have pointed out the lax oversight the FDA practices on orphan drug development and the various ways in which developers are abusing the incentives available to them.2

The Rare Diseases Program has obviously jump started a movement towards increased development of orphan drugs. While most of the program’s impact has been positive, it remains necessary to ensure a streamlined review system. This will help developers and healthcare professionals make better medical decisions for their patients.

References

  1. Tribble, S. and Lupkin, S. (2017). High Prices for Orphan Drugs Strain Families and Insurers.  Kaiser Health News. Retrieved from: http://www.npr.org/sections/health-shots/2017/01/17/509507035/high-prices-for-orphan-drugs-strain-families-and-insurers [Last accessed 13/03/2017].
  2.  Institute of Medicine (US) Committee on Accelerating Rare Diseases Research and Orphan Product Development; Field M.J., Boat T.F., Rare Diseases and Orphan Products: Accelerating Research and Development. Washington (DC): National Academies Press (US); 2010. 3, Regulatory Framework for Drugs for Rare Diseases. Available from: https://www.ncbi.nlm.nih.gov/books/NBK56185/ [Last accessed 13/03/2017].

Rare Diseases at a Glance from the Viewpoint of the European Medicines Agency (EMA)

Source: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000029.jsp

Gobal dimension

Because rare diseases are a global issue, the Agency works closely with its international partners on the designation and assessment of orphan medicines, in particular:

the United States Food and Drug Administration (FDA), sharing information on orphan medicines under their confidentiality arrangement. The two authorities have also developed common procedures for applying for orphan designation and for submitting annual reports on the status of development of designated orphan medicines.
the Japanese Ministry for Health, Labour and Welfare (MHLW) on issues related to orphan medicines.
The Agency works with organisations representing patients with rare diseases through the European Organisation for Rare DiseasesExternal link icon (EURORDIS). 

Rare diseases at a glance 

Between 5,000 and 8,000 distinct rare diseases exist, affecting between 6% and 8% of the population in total – in other words, between around 27 million and 36 million people in the EU. Most people suffer from diseases affecting fewer than 1 in 100,000 people.
80% of rare diseases have identified genetic origins, and affect between 3% and 4% of births. Other rare diseases are due to degenerative and proliferative causes.
Symptoms of some rare diseases may appear at birth or in childhood, including spinal muscular atrophy, lysosomal storage disorders, patent ductus arteriosus (PDA), familial adenomatous polyposis (FAP) and cystic fibrosis. More than half of rare diseases appear during adulthood, such as renal-cell carcinoma, glioma and acute myeloid leukaemia.
Medical and scientific knowledge about rare diseases is lacking. The number of scientific publications about rare diseases continues to increase, with an average of 5 new diseases described every week in the medical literature. However, fewer than 1,000 diseases benefit from even minimal amounts of scientific knowledge. These tend to be the rare diseases that occur most frequently.

GOP Senators Ask GAO To Investigate High Prices For Orphan Drugs

By: Sarah Jane Tribble & Sydney Lumpkin

Source: NPR - http://www.npr.org/sections/health-shots/2017/03/07/518980280/gop-senators-ask-gao-to-investigate-high-prices-for-orphan-drugs

Building on weeks of mounting pressure to address high prescription drug prices, three influential U.S. senators have asked the government's accountability arm to investigate potential abuses of the Orphan Drug Act.

In a letter to the U.S. Government Accountability Office, Sens. Orrin Hatch, R-Utah, Chuck Grassley, R-Iowa, and Tom Cotton, R-Ark., raised the possibility that regulatory or legislative changes might be needed "to preserve the intent of this vital law" that gives drug makers lucrative incentives to develop drugs for rare diseases.

Source: https://rarediseasesrarefunding.wordpress.com/2016/04/25/what-are-orphan-drugs-and-why-are-they-necessary/

Source: https://rarediseasesrarefunding.wordpress.com/2016/04/25/what-are-orphan-drugs-and-why-are-they-necessary/

"While few will argue against the importance of the development of these drugs, several recent press reports suggest that some pharmaceutical manufacturers might be taking advantage of the multiple designation allowance in the orphan drug approval process," the letter published Friday states.

In January, NPR published a Kaiser Health News investigation that found the orphan drug program is being manipulated by drug makers to maximize profits and to protect niche markets for medicines being taken by millions.

Congress overwhelmingly passed the 1983 Orphan Drug Act to motivate pharmaceutical companies to develop drugs for people whose rare diseases had been ignored. Drugs approved as orphans are granted tax incentives and seven years of exclusive rights to market drugs that are needed by fewer than 200,000 patients in the U.S.

In recent months, reports of five- and six-figure annual price tags for orphan drugs have amplified long-simmering concerns of abuse of the law. The senators' call for a GAO investigation reflects that sentiment.

The senators asked the GAO for a list of drugs approved or denied orphan status by the Food and Drug Administration. It also asked whether resources at the FDA, which oversees the law, have "kept up with the number of requests" from drug makers and whether there is consistency in the department's reviews.

The Kaiser Health News investigation found that many drugs that now have orphan status aren't entirely new. More than 70 were drugs first approved by the FDA for mass-market use. Those include cholesterol blockbuster Crestor, Abilify for psychiatric disorders and rheumatoid arthritis drug Humira, the world's best-selling drug.

Others are drugs that have received multiple exclusivity periods for two or more rare conditions. About 80 drugs fall into this category, including cancer drug Gleevec and wrinkle-fighting drug Botox.

Hatch, a longtime advocate of the rare disease community, said late Monday in a statement that there was little evidence so far to suggest the Orphan Drug Act needs to change.

Hatch is chairman of the Senate Finance Committee, which oversees 50 percent of the federal budget, including Medicaid and Medicare spending. He said the letter is requesting "the first GAO study exclusively reviewing the Orphan Drug Act, and such oversight will ensure those critical innovations are continued into the future."

Grassley, the senior senator from Iowa, chairs the Judiciary Committee and has jurisdiction over anticompetitive and patent-related issues. Grassley last month announced an inquiry into the Orphan Drug Act in response to the Kaiser Health News investigation.

Cotton, a strong conservative voice, chairs the subcommittee on economic policy under the Committee on Banking, Housing and Urban Affairs. In a floor speech last month, he announced that he would find a legislative solution to price hikes associated with the orphan drug program.

Cotton focused on an orphan drug that has been a flashpoint in the national dialogue about drug prices, arguing that the seven-year marketing exclusivity offered by the law should not have been given to Emflaza, a corticosteroid approved to treat Duchenne muscular dystrophy. Emflaza was not mentioned in the letter to the GAO.

"Monopoly rights are not merit badges," Cotton said in his speech. "They're not a reward for business smarts. They're supposed to serve the interests of patients."

The U.S. distributor of Emflaza, Marathon Pharmaceuticals, triggered an uproar when it announced an $89,000 annual list price for the drug, which many U.S. patients have purchased overseas for $1,000 to $1,600 a year.

Marathon responded in February by delaying the rollout of the drug, saying it will talk with stakeholders, including patients, about the price.

Kaiser Health News is an editorially independent news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

KHN's coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation.

Global orphan drugs market to reach $ 209 billion by 2022

Worldwide orphan drug sales forecast to total $ 209 billion (growing at CAGR of 11.1 percent from 2017 to 2022); approximately double overall prescription market growth, according to Evaluate latest report ‘EvaluatePharma Orphan Drug Report 2017’. 

The market for orphan drugs, which are pharmaceutical product aimed at rare diseases or disorders, is set to be 21.4 percent of worldwide prescription sales by 2022 (excluding generics). At the same time, median cost per patient differential will be 5.5 times higher for orphan drugs compared to non-orphan.

According to the report, in the last 12 months, there has been an increase in scrutiny of the price of these lifesaving products. 

“The image of the plucky small biotech striving to develop treatments for the rare diseases largely ignored by big pharma is long gone. Instead, this year we again find big pharma dominating the sector. Seven of the top 10 companies by orphan drug sales are global industry players”, said Lisa Urquhart, EP Vantage editor and report contributor. 

“And the pricing incentives are substantial. Of the top 100 drugs in the US the average cost per patient per year for an orphan drug was $140,443 in 2016, compared with $27,756 for a non-orphan, putting pressure on the industry to continue to generate innovations that justify the huge costs of treatments”, added Andreas Hadjivasiliou, report author and EvaluatePharma analyst.

The report anticipates Celgene to overtake Novartis as the world’s number one orphan drug company in 2022, climbing two places, and pushing Novartis down to number three. Besides, one product to contribute the majority of orphan sales for two of the top four; Celgene (Revlimid, 80 percent of sales) and BMS (Opdivo, 68 percent of sales).

EvaluatePharma report finds that Opdivo is Europe’s largest orphan drug in 2022, with sales of $ 2.4 billion for all indications. All of the orphan drugs in the top 10 are already marketed, with all but one forecast to continue to grow through to 2022. Orphan drugs are set to account for 55 percent of the cumulative value of the European pipeline through to 2022. Orphan products forecasted to launch in the coming years are expected to grow at a CAGR of 116 percent compared to non-orphan pipeline drugs which are forecasted to grow at 95 percent CAGR.

How to Prepare a Pre-Request for Designation (Pre-RFD): Draft Guidance for Industry

This guidance is intended to assist sponsors in obtaining a preliminary assessment from the U.S. 
Food and Drug Administration (FDA or Agency) through the Pre-Request for Designation (Pre-RFD) process. The Pre-RFD process is available to provide informal, non-binding feedback regarding the regulatory identity or classification of a human medical product as a drug, device, biological product, or combination product.  In addition, this informal process provides information about a non-combination or combination product’s assignment to the appropriate Agency Center (Center for Drug Evaluation and Research (CDER), Center for Devices and Radiological Health (CDRH), or Center for Biologics Evaluation and Research
(CBER)) for premarket review and regulation.  Specifically, this guidance explains the Pre-RFD process at the Office of Combination Products (OCP) and helps a sponsor understand the type of information to
provide in a Pre-RFD.    

Additional information on topics outside the scope of this guidance may be found on our website
(at http://www.fda.gov/CombinationProducts/default.htm.)  These topics include the definitions
of a non-combination and combination product, as well as information about the formal Request
for Designation (RFD) process. 

Part 3 FDA Expedite Programs Series: Fast Track Designation

Objective
To facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. 

Criteria
An unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially better than available therapy. If there are available therapies, a fast track drug must show some advantage over available therapy, such as:

  • Showing superior effectiveness, effect on serious outcomes or improved effect on serious outcomes
  • Avoiding serious side effects of an available therapy
  • Improving the diagnosis of a serious condition where early diagnosis results in an improved outcome
  • Decreasing a clinical significant toxicity of an available therapy that is common and causes discontinuation of treatment
  • Ability to address emerging or anticipated public health need

Potential Benefits

  • More frequent meetings with FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval
  • More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
  • Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
  • Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA

Fast Track Designation Process

  • Request may be submitted when the IND is first submitted or any time prior to pre-BLA or pre-NDA meeting. Decisions are made within 60 days from submission
  • Particulars are found in Guidance for Industry: Expedited Programs for Serious Conditions – Drugs and Biologics (2014)

Orphan drug sales will outpace all other meds, thanks to high prices

By: Ed Silverman

Source: Pharmalot https://www.statnews.com/pharmalot/2017/02/28/orphan-drugs-prices/

As payers continue to foot the bill for orphan drugs, sales of these rare disease treatments are forecast to grow 11 percent over the next five years — to $209 billion. And this is more than twice the expected increase in sales of all other prescription medicines, according to a new analysis.

By 2022, orphan drugs are predicted to account for more than 21 percent of worldwide brand-name prescription drug sales, up from 6 percent in 2000. Last year, sales of orphan drugs, which are used to treat rare diseases for patient populations numbering less than 200,000, climbed more than 12 percent, to $114 billion. By comparison, sales of other brand-name drugs rose 2.4 percent, to $578 billion.

Source: Spectrumnews.org

Source: Spectrumnews.org

The figures indicate that orphan drugs remain a lucrative revenue stream for the pharmaceutical industry, especially the largest drug makers. Based on worldwide orphan drug sales, seven of the 10 largest players are global companies, including Novartis, Roche, and AbbVie, not upstart biotechs, according to the analysis, which was conducted by EvaluatePharma, a market research firm.

The data indicate that the pharmaceutical industry is aiming to satisfy unmet medical needs, but the data, which was released to coincide with Rare Disease Day, also emerges amid growing controversy over orphan drugs. Large price tags are drawing attention and there is growing concern that some drug makers are exploiting loopholes in a US law, which has prompted one lawmaker to start a probe.

The latest example of a sky-high price occurred two months ago, when Biogen won regulatory approval for a spinal muscular atrophy drug called Spinraza and set a price that few expected — $750,000 for the first year of treatment and $375,000 each year thereafter. One analyst suggested the “sticker shock” may cheer investors, but also invite criticism amid growing outrage over drug pricing.

Meanwhile, Senator Chuck Grassley (R-Iowa) is investigating whether some drugs may have been submitted for FDA approval with the ultimate intention of being used more broadly than if they were designed only for the rare disease populations. “I’m interested in learning whether the unanticipated uses of the provisions are contributing to high prices for commonly used drugs,” he said earlier this month.

Concerns were further raised when another company, Marathon Pharmaceuticals, this month won orphan status for an older drug for treating Duchenne muscular dystrophy and set an $89,000 price tag. Generic versions have been available for about $1,000 from other countries, but Marathon will have seven years of market exclusivity, and Americans will not be able to buy from overseas. And Grassley noted that Marathon did not develop the drug.

The new analysis notes, however, that “pricing incentives are substantial.” Of the top-selling 100 drugs in the US, the average cost per patient per year for an orphan drug was $140,443 in 2016, compared with $27,756 for a non-orphan. And the median cost per patient differential was 5.5 times higher for orphan drugs last year compared to non-orphan drugs.

Nonetheless, a survey last fall of 36 payers that cover more than 74 million patients in the US found their coverage policies are unlikely to change much over the next six years. For instance, there was only a 19 percent chance that policies would tighten by 2018, a 25 percent chance that such a change would occur by 2020, and a 33 percent probability of a policy change by 2022.

Whether this trend will change is uncertain. The Sprinraza drug has become a closely watched bellwether in the national debate over drug prices. UnitedHealthcare agreed to cover the med and its policy is less restrictive than one disclosed recently by Anthem. Even so, UHC will set limits and will only pay beyond an initial handful of doses only if doctors can prove the drug is working.

But while high prices contribute to national anxiety over the cost of prescription medicines, orphan drugs are also a politically sensitive topic, since some medicines are meant for small, seriously ill populations. And while insurers may create hurdles to coverage, the number of patients may be small enough to avoid major battles that can generate outsized negative publicity.

This helps explain why drug makers are rushing to win regulatory approval. Last year, for instance, there were 582 requests by companies for an orphan designation by the Food and Drug Administration, a stunning 23 percent increase from 2015 and triple the number of requests that were made a decade ago, according to the FDA Law Blog.

Meanwhile, more orphan drugs are winning the coveted designation. The total last year amounted to 333, down slightly from 354 in 2015, but the second-largest number ever. Although the number of orphan drugs approved last year was 39, which is less than the two previous years, this was also the third-largest tally ever.

Investors are taking notice. Oncology drugs were a dominant area of focus in mergers and acquisitions, but rare disease drug deals now outpace meds for the central nervous system, dermatology, metabolism, and other categories, according to SunTrust Robinson Humphrey.  The mean transaction size for orphan drug deal was $3.1 billion, which was larger than the biotech sector overall, at $2.6 billion.

Just the same, Evaluate Pharma cautions that the sky may not be the limit. “If the orphan drug industry is to continue to thrive it must continue to generate innovations that justify the huge cost of these life-transforming treatments,” the firm concludes.

Here are a few other nuggets from the report:

  • In the US, the biggest-selling orphan drug last year per patient was Soliris, an Alexion Pharmaceuticals medication used to treat two rare diseases, at more than $400,000 per patient.
  • Also in the US, the biggest-selling orphan drug, based on total revenue, was Revlimid, a Celgene treatment for cancer, at $4.4 billion.
  • And among companies selling orphan drugs for diseases other than cancer, Shire has the largest sales volume on a global basis with $5.3 billion.

Ed Silverman can be reached at ed.silverman@statnews.com
Follow Ed on Twitter @Pharmalot