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02/23/2024 21:33:23

Feature

Clinics ration supplies as cancer drug shortages proliferate

While drug shortages have been a major cause for concern over the past few years, Sally Turner writes that medications to treat cancer are in particularly short supply.

Drug shortages have been in the news for several years, but they worsened during the Covid-19 pandemic, and several pharmacy, regulatory, and physician organisations, in the US and Europe, have recently issued alerts in response.

In May, the American Cancer Society declared that chemotherapy drugs were among the top-five drug classes affected by shortages, and numerous oncology medications are currently in short supply according to data from the US Food and Drug Administration (FDA).

The shortages of oncology drugs are primarily in the generic drug market.

Dr. Kevin Shulman, professor at the Clinical Excellence Research Center at Stanford University

“The shortages of oncology drugs are primarily in the generic drug market,” says Dr. Kevin Shulman, a professor of medicine and clinical hospitalist at the Clinical Excellence Research Center at Stanford University. There is no financial incentive for big pharma to manufacture older generic medications that are critical to the treatment of several common cancers and very few companies invest in doing so, says Dr. Kristen Rice, medical oncologist with a practice in San Diego, California.

“We have consolidated drug purchasing in the US to drive down acquisition prices of these already low-cost medications. Unfortunately, this market functions based solely on price, not product quality or supply chain quality.”

This has led to drug shortages when the price is reduced, as it drives suppliers out of the market. He adds that by not having a robust and diverse supply chain, the US is extremely vulnerable to manufacturing quality issues when it comes to the remaining suppliers in the system.

“We need the market to trade-off price and quality, and we need health systems to change their procurement models to emphasise product and supply chain quality,” he explains. Rice, who has hands-on experience dealing with this current shortages, agrees with Shulman and adds that the regulatory framework lacks the ability to ensure that critical medications are produced in quantities sufficient to meet the needs of the US population.

‘None of the expensive new cancer drugs are in shortage’

While clinicians are used to dealing with shortages, these have gotten particularly difficult in recent times. Rice describes the recent experience of trying to access the chemotherapy drug “capecitabine, a generic version of Roche’s Xeloda. “They were going to charge us over $12,000 for a cycle [of chemotherapy] that would have cost a few hundred dollars before the shortage. None of the expensive new drugs are in shortage.” Rice says these shortages are happening because American drug manufacturers are allowed to manipulate the supply of critical medications to drive up demand and create panic.

They were going to charge us over $12,000 for a cycle [of chemotherapy] that would have cost a few hundred dollars before the shortage.

Dr. Kristen Rice, medical oncologist

The most critical shortages are of cisplatin and carboplatin, which are among the most effective cytotoxic medications available and are central to most chemotherapy regimens. Cisplatin, for example, is in short supply because of a quality control problem that resulted in a shutdown at one of the few companies that produces cisplatin, explains Rice. “There are numerous other shortages; the looming shortage on 5-fluorouracil (5FU) is particularly concerning because there is also a shortage on capecitabine, which is our usual substitute when 5FU is short.”

Rice says her clinic has also been dealing with a reduced supply of generic nab-paclitaxel for months, but the branded version, Celgene’s Abraxane is still available at a higher cost. There are also shortages of docetaxel, doxorubicin, and dacarbazine.

Rationing drugs

Earlier this year, the American Society of Clinical Oncology (ASCO) issued new guidelines for physicians on how to respond to these shortages, specifically in relation to treating gastrointestinal cancers.

Because critical drugs are in short supply or simply not available, Rice says they have started “trimming doses” to spread the available supply across more patients. The clinic is prioritising patients who have curable cancers, which means those with stage-IV cancer may receive lower than recommended doses or have treatments delayed.

She adds that for many of these drugs, there are no suitable alternatives and for others the alternatives are also in short supply:

“In the case of cisplatin and carboplatin, they are interchangeable, which is why both are now in shortage, says Rice. While oxaliplatin can be substituted for cisplatin and carboplatin in some cases, it causes side effects like neuropathy which cisplatin and carboplatin don't have. “For example, we have no data for the use of oxaliplatin in lung cancer, and if we combine it with paclitaxel, the patient could develop crippling neuropathy.”

Credit: Shutterstock/ Alan Sau

While 5FU and oral capecitabine are interchangeable, they are both now in short supply, says Rice, and there is no substitute for doxorubicin or dacarbazine.

Most of these drugs are ‘first line’ treatments for cancer, meaning that they are the best available treatments, and the other options available are less likely to be effective.”

At Rice’s practice, staff has had to order essential drugs several weeks ahead and stockpile treatments in order to manage the situation. They are also reducing doses and delaying treatments to allow more time to try to acquire the necessary drugs. In some cases, they are having to send patients to other clinics that have more of the necessary drugs stockpiled.

Most of the drugs in shortage are ‘first line’ treatments for cancer, meaning that they are the best available treatments, and the other options available are less likely to be effective. “On the east coast in the US, many practices have stopped treating incurable patients altogether,” claims Rice.

Tough to implement solutions

Understandably, Rice and her fellow oncologists are frustrated about the current situation and are calling for a long-term solution. A white paper report in 2021 proposed six key actions to mitigate ongoing drug shortages, which included reforming stock allocation strategies and introducing incentives for manufacturers, among others.

Still, shortages persist. Rice says that she and her colleagues struggle through a shortage but then when the crisis is averted (and patients are safe again) they focus back on the day-to-day because they don’t have the time and resources to consistently push for change.

“I don't know why patients aren't angrier about [the system]. The only explanation I can think of is that they don't know. Nobody is making sure enough medication gets produced to treat everyone who needs it.”

“We are not going to accept this as the new normal and just move on. The current system is broken and needs to be fixed.”

02/23/2024 21:33:23

Feature

Asian countries prioritise rare disease market access amid stark disparities

Ahead of APEC’s "Rare disease vision 2025" deadline, Asian countries are working at different speeds towards improving drug market access. By Akosua Mireku and Irena Maragkou.

In Asia, cultural and logistical factors have governed market access to rare disease drugs. Credit: pogonici via Shutterstock

Five years ago, the Asia-Pacific Economic Cooperation (APEC), an intergovernmental forum for 21 member economies in the

Asia-Pacific Region, released an action plan for rare diseases. The goal of the initiative was to address barriers to healthcare and social welfare services for individuals affected by rare diseases leading up to 2025. With less than two years left for APEC’s deadline, certain areas in the region have made progress on their plans to improve access while others lag behind.

The rare disease drug market has steadily grown in the last decade as the FDA built frameworks to encourage the development of rare disease drugs. The Orphan Drug Act of 1983 was one of the first steps taken to incentivise drugmakers to prioritise rare diseases in their pipelines, giving companies marketing exclusivity for additional years before generics enter the market. Since then, the FDA has adopted a priority review voucher program that expedites the orphan drug regulatory process and periodically releases action plans and new legislations on rare disease research. GlobalData found that the US has approved a particularly wide range of rare disease therapies, ranging from preventative treatments for infectious diseases to dermatological medicines.

There is a very limited government role regarding patient access to rare disease treatments in Indonesia.

Chia Hsuan Lin, a GlobalData analyst

In Asia, cultural and logistical factors have governed market access to rare disease drugs. For example, China has devised a system to simplify the rare disease review process via its National Healthcare Security Administration. Chia Hsuan Lin, a GlobalData analyst, says China’s National Medical Products Administration is usually very adept at negotiating therapy prices with manufacturers to ensure that therapies on China’s National Reimbursement Drug List are heavily discounted. This is in contrast to other markets such as the US, she adds in an email.

However, the approach in Indonesia differs massively. Lin says, “Indonesia provides limited public health insurance coverage in general. There is a very limited government role regarding patient access to rare disease treatments in Indonesia.”

Looking at India’s rare disease drug landscape, Sanobar Syed, the associate director of market insights and strategy at Beigene, says the region suffers from very low medical awareness surrounding several rare diseases. “Rare diseases are very difficult to manage in the area, specifically in India, due to the socioeconomic disparities between the regions,” she says, adding this also plays a role in the lack of diagnosis, which is an issue that affects many other countries within the region.

In this exclusive analysis, Pharmaceutical Technology analysed data from GlobalData's Drugs database and Price and Intelligence database to investigate different aspects of rare disease market access in comparison to the US, which is one of the biggest markets for such specialised drugs. Indonesia, India, and China were chosen as examples to demonstrate the diversity of rare disease pharmaceutical regulations across the continent and incorporate economic status as a factor in this analysis.

Market access risk scores are calculated using qualitative and quantitative factors that affect market access in each country. This is represented on a logarithmic scale of 1–10 to show a country’s ability to grant market access, with one correlating with low risk and 10 meaning extreme risk.

Barriers to access

Among the 10 pillars of APEC’s 2025 action plan, major points include “defining rare diseases and orphan products with policies and processes”, “raising public and political awareness of rare disease issues”, and “delivering new and accessible treatments to patients.”

In the developed world, self-care advocacy groups and patient support programs are a useful route to market.

Sanobar Syed, associate director of market insights and strategy at Beigene

APEC also highlighted the need to overcome issues with rare disease diagnostics. Syed says delayed and wrongful diagnosis is a major issue in some parts of India where people do not have routine access to medical checkups. Thus, statistics for disease prevalence can often be incorrect, misrepresenting the unmet need and potential market size for rare disease therapies. David Dodd, CEO of the biotech GeoVax Labs, which is developing vaccines for rare infectious diseases, says one of the first things his company looks at is the unmet need in the area. The analysis found that there is a high volume of vaccines available in Indonesia and India compared to other drug and therapy types, which is in line with the higher burden of rare infectious disease in these regions.

Dodd says, “If I’m at a smaller company I’m going to look for these areas that are rare diseases, orphan drugs, niche markets because that provides me an opportunity to be the leader within that area and be successful. It also means that we can develop relationships with those in those regions.”

Syed explains that India’s pharmaceutical industry is mostly ruled by a private market, making some traditionally expensive orphan drugs, like gene therapies, inaccessible in the area. It is the same case in Indonesia. Organisations such as the Vaccine Alliance (GAVI) help with access to vaccines in such countries, but treatments for rare diseases do not receive the same benefit.

Syed says, “In the developed world, self-care advocacy groups and patient support programs are a useful route to market.” However, in India, there are a lot less of these organisations available to help companies launch their rare disease drugs or help with running clinical trials compared to the US, she adds. Omar Khadr, a GlobalData analyst specialising in Indian market access, tells Pharmaceutical Technology, “Some ad hoc patient access schemes do exist, but these are funded through charitable schemes such as the India Charitable Access Program by Sanofi, which provides free enzyme replacement therapy to patients with lysosomal storage disorders.” This includes treatment with Sanofi’s Pompe disease therapy Nexviazyme (avalglucosidase alfa-ngpt) which received FDA approval in 2021. The therapy is a recombinant protein that replaces the defective acid alpha glucosidase enzyme in patients with Pompe disease.

Changing approaches to rare disease market access

As a middle-income country, India’s rare disease regulatory framework is still in the early stages. Khadr says, “There is no official reimbursement policy or coverage in this sector. No regulations are currently governing patient access programs and risk-sharing or managed-entry agreements for these drugs.” However, in 2019, positive steps were made towards access to orphan drugs with the launch of a regulatory framework that allows manufacturers or sponsors of orphan drugs to apply to the licensing authority in India for an expedited review process. This removes the requirement for local clinical trials under certain conditions.

Furthermore, a national rare disease policy, which was approved in 2021, will see Indian authorities forming a special committee that reviews patients’ applications for financial coverage of orphan drugs. “If these applications are approved, the government could offer coverages up to $60,000 for orphan diseases treatment. However, hundreds of applications were sent to the government in the last two years and are still pending,” said Khadr.

China’s approval of rare disease drugs has seen an upward trend in recent years. A 2021 report found that 64 out of 74 approved orphan drugs were affordable to rural/urban residents with the National Basic Medical Insurance considered, showing an increase of 14.1% from 2017 to 2020. This comes after China established the Compendium of China’s First List of Rare Diseases (CLRD) in 2018, consisting of 121 rare diseases. Since then, authorities have the National Network to Collaborate on Diagnosis and Treatment of Rare Diseases (NCDTRD) in 2019 and more initiatives have followed. Of the four countries included in this analysis, GlobalData found that China had the highest proportion of rare disease drugs, making up 35% of its approved drugs.

Dodd highlights a noticeable change in investor interest in marketing rare disease drugs in areas such as India and Indonesia. “[Five years ago] if I talked to people about rare diseases in regions south of the equator, US investors dismissed it, questioning how you [biotechs] would make money. Now there is recognition that there can be significant value in these areas, so now I don’t encounter these discussions,” says Dodd.

Since the 2017 APEC meeting, the organisation has begun working towards establishing a Rare Disease Registry Network and a framework for collaboration between the companies. In a 2018 press release, Cameron Milliner, APEC LSIF Rare Disease Network Industry’s co-chair said, “Together, we aim to build the link to connect local rare disease policies with transformational solutions, and effective care management with the patient’s voice.”

02/23/2024 21:33:23