As originally reported in Medscape; many rare disease patients know the frustration of not having any drugs or treatments available for their disease. 95% of rare disease patients have no pharmaceutical options. Reasons for this consist of the small populations for trials, limited research, lack of funding.
For some patients, there is another major hurdle to receiving life-saving treatments: access. This is when patient do not receive a drug not for lack of treatment options, but lack of available treatment options. There may be a single treatment option that could help your chronic illness, but it has not been approved in your locality. A treatment option exists, but it’s just out of reach, it is not available for you.
That was the case for rare chronic hypoparathyroidism with the pharmaceutical Natpar or Natpara. The drug’s story shows a few of the sticky points that prevent orphan drugs from being approved, preventing rare disease patients from accessing them. There are not many patients to run local trials on, it is expensive, it was made with faulty equipment and recalled. The drug manufacturer claims the local hoops and hurdles to prove safety and effectiveness are too high for rare disease drugs which have less patients to gather evidence from.
Hypoparathyroidism
Chronic hypoparathyroidism is a rare endocrine disease in which the body has low levels of calcium, and causing a deficit in the parathyroid hormone. These hormones regulate the metabolism and chemical processes that effect some of the bodies functions such as heart rate, body temperature, and blood pressure. This can result in weakness, headaches, or muscle’s having cramps, spasms, twitching, numbness, or tingling. Treatment includes calcium supplements and active vitamin D. However, Narpar, the new injectable recombinant parathyroid hormone, effectively treats mores severe cases.
Narpar
The drug was full of potential, hotly anticipated by patients who currently do not have any very effective drugs. Liz Glenister, founder and CEO of the relevant charity Parathyroid UK, explained, “The reason we need it is because the current therapy is not adequate; it was never devised for this condition and it can lead to quite severe renal outcomes.” After six years, there were positive results in the US. As reported by Medscape Medical News, “results in 34 patients showed the drug was associated with a 40% reduction in oral calcium supplementation doses and a 72% reduction in calcitriol doses, while albumin-corrected serum calcium levels were maintained within target levels.” Before Narpar, the treatment options were limited. Additionally, Glenister mentions that managing a patient is ” “very much guesswork on the part of the doctor and the patient, it’s a very difficult condition to manage.”
It began to be made available in other countries: Norway, Finland, Sweden, Denmark, Israel. Patients in other countries thought it would make its way onto the market for them soon too.
Access Issues to Narpar
Access looked different for patients on each side of the Atlantic, but each ultimately resulted in failure to receive reliable access to the drug.
The US
After patients in the states received approval in 2015, the patients were excited. The rest of the world thought this set the precedent for them next, soon to receive the treatment option. Glenister explained, “From the patient’s point of view, it was absolutely wonderful: ‘like a lightbulb going on,’ people said.”
However, after years of success, in 2019, the drug was recalled due to safety concerns. It seemed the drug’s cartridge had been contaminated, making it unfit for consumption. However, the withdrawal from a medication is also a safety concern: many American patients who lost their access to the drug suffered. Some had to be hospitalized from the withdrawal which caused severe hypocalcemia. Having a reliable medicine is important. Going on and off medications is not easy. Patients do not want their health to swing back and forth with faulty equipment or in other cases with public policy budgeting or heightened clinical standards.
Why Europe Can’t Access the Drug
While patients in Europe waited, it began to seem as approval would never come. This came from a host of issues: small sample sizes, high prices, limited data. While the patient experience has reportedly been very positive, this was not enough to push it through the bureaucracy of regulatory authorities.
Across Europe
While in 2017, Europe’s regulatory agency, the European Medicines Agency (EMA), approved Natpar, they subsequently suspended the drug’s appraisal because of the “relatively small” size of the phase 2 study. As typical for rare diseases, there are not large of patient pools to get a representative patient sample. This is the sticky point for the manufacturer, and in some other cases of access issues for rare disease drugs. They believe the bar is too high for these orphan drugs. In their experience, rare disease patients without treatment options would rather try, and thus far, their patient feedback is overwhelmingly positive. Of course, regulation is pertinent before funding. However, it needs to practically adapt to the reality that orphan drugs necessitate a different standard.
While there is an ongoing registry that is collecting data on the drug which is in a phase 4 study, the problem is that until the drug is approved, there is not reimbursement, so many patients can not pay the current steep prices. Thus it is a self-perpetuating cycle: until the treatment is approved, the cost will be excessively high, so patients will not use the drug, and there is not enough data to collect.
The UK
In 2017 the UK’s National Institute for Health and Care Excellence (NICE), the institute responsible for recommending drugs, told the National Health Service (NHS) that it would be appropriate to have an appraisal conducted. However, by 2018, NICE suspended this too because of the EMA’s decision for Europe. Since then, the drug has not made any progress through the healthcare system. Takeda will only approach them again when it has obtained a large amount of data to meet the high bar.
There are individual patient who have gotten access to the drug, such as through Individual Funding Requests or local funding. However, wider access through the states health system was never provided. It is not enough to be made available to a few privileged patients. Dr. Simon Meadowcroft of the drug’s manufacturer, Takeda Pharmaceuticals, UK told Medscape while some patients can privately access the drug, they want to make sure the government’s health program, the NHS will be providing reimbursements so more patients will have access.
Expenses and other barriers
Others question whether the lack of access is more a decision made out of consideration of the drug’s high cost rather than its effectiveness. In Spain for example, Glenister says the spotty access seems to be correlated to zip code. Basically, if your locality will pay for it, you’re the lucky one. Canada’s Dr. Aliya Khan, who is involved in the global trials, say this will not be the case for Canada. They lack access because the drug has not yet been submitted for approval, the reasons are unclear as to why. However, Khan said once it’s approved, it will be paid for. Whether that be on a funded process or on compassionate release, this will join the other expensive drugs their health system funds.
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Regulatory bodies have a powerful role: they decide whether and when patients get life-changing drugs. A hard part of being rare is that the system is built for the common- larger diseases with larger patient sizes. Rare diseases need a system thats adaptable to their needs too; one of which provides reliable access to suitable treatment options. In each of these countries stories, there are examples of different barriers: poor equipment, slow regulatory processes, small sample sizes, localities not wanting to pay the high costs. Each of which have stopped patients with hypoparathyroidism from getting full access to Narpar.
