Pharmaceutical companies are racing to find vaccines, treatments, and cures for the new coronavirus by researching new-in-kind compounds and testing compounds that have already been assessed—and in some cases approved—to treat other existing conditions.
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The novel drug process can be time-consuming
Some companies, including Eli Lilly, Regeneron, and Takeda, are developing new treatments for people already infected with the new coronavirus. Others, such as Moderina, GlaxoSmithKline, and Inovio Pharmaceuticals, are developing novel vaccines for prevention. Johnson & Johnson, Pfizer, and Sanofi are working on both novel treatments and vaccines, according to STAT News' Damian Garde.
However, due to the lengthy nature of pharmaceutical drug development it might be months before novel treatments are tested in human clinical trials, and even longer until FDA approval. That's in part because new drugs or vaccines must undergo a series of tests in lab experiments and animals to prove that they are safe before they can be tested in a human trial. For example, Regeneron said human clinical trials for their drugs could begin by early summer.
Researchers turn to existing drugs with a potential faster turnaround time
On the other hand, existing drugs—either previously tested and/or approved to treat other conditions—already have evidence to demonstrate that they are safe in humans. Therefore, manufacturers don't need to re-prove safety when assessing efficacy in coronavirus and can test those drugs more quickly. However, researchers still must carefully assess them for effectiveness and safety to ensure they do not cause unnecessary harm to patients infected by the new coronavirus—especially when administered at varying dosage levels, to patients with different demographics or preexisting conditions, and/or in conjunction with other drugs.
Two drugs that appear promising are chloroquine (and a closely related compound, hydroxychloroquine) and Remdesivir. Chloroquine is an anti-malarial drug developed by Rising Pharmaceuticals, and hydroxychloroquine is a related anti-malarial drug (also approved to treat lupus and rheumatoid arthritis) by Mylan and Teva Pharmaceuticals. Remdesivir is Gilead's experimental antiviral drug, previously studied (but never approved) to treat Ebola.
Manufacturers are preparing to scale up production and distribution of these existing drugs for clinical trials and treatment (if approved). Rising Pharmaceuticals recently cut the price of chloroquine in half in response to the global pandemic. The Feinstein Institute for Medical Research at Northwell Health recently launched three clinical trials targeting coronavirus with Regeneron and Sanofi's antibody treatment, Sarilumab, and Gilead's Remdesivir. The World Health Organization also launched a global megatrial, named SOLIDARITY, of Remdesivir, chloroquine and hydroxychloroquine, and two other compound treatments.
However, some of these drugs are known to cause serious adverse events. For example, chloroquine is known to cause nausea, diarrhea and tinnitus in the short-term, and can irreversibly impair eyesight and cause heart problems in the long-term. Chloroquine also has a risk of overdose, which may be fatal. An Arizona couple accidentally poisoned themselves after self-medicating with chloroquine—the man died from cardiac arrest, and his wife (who is now in stable condition) was initially listed in critical condition. Therefore, controlled clinical trials and robust data will be necessary to determine whether these drugs live up to their promise—and to assess whether the potential benefits outweigh the risks.
While the expedited pace of scientific innovation is promising, any drugs or vaccines to treat COVID-19 will ultimately need FDA approval, and many open questions about access, pricing, and appropriate use remain.
3 questions that will impact how potential coronavirus treatments get to patients.
1) How much efficacy data will FDA require before approving drugs for COVID-19?
President Trump announced that he's encouraging FDA to review hydroxychloroquine under FDA's Fast-Track program, which expedites the evaluation of new drugs that can treat serious or life threatening conditions or address unmet need. It's likely that other drugs will undergo a similar approval process in order to treat the new coronavirus. However, the amount of data that will be required to move drugs to treat the coronavirus through Fast-Track remains unclear.
To facilitate rapid evaluation of drug efficacy, it will be essential that FDA consider a wide array of data sources. Traditionally, FDA does not consider data from other countries during the processes of drug development and approval, and instead relies on U.S.-based clinical trials. So it's interesting to see that FDA is "leveraging scientific information about the virus and trials currently being conducted in other countries such as China, Japan, South Korea and Italy as well as in the U.S" to support their evaluation of treatment efficacy and safety.
In addition to clinical trials, it will be essential that manufacturers collect real world evidence—evidence outside of a traditional clinical trial—to monitor and assess drug safety and efficacy on an ongoing basis. This will enable researchers and physicians to make more accurate risk-benefit assessments and determine appropriate prescribing.
2. When (and if) drugs are approved, how will we ensure patients actually receive these drugs?
In addition to ramping up production of existing drugs, pharmaceutical companies are gearing up their manufacturing capabilities in preparation of new drug approvals. However, as the new coronavirus exponentially affects the United States and other countries, pharmaceutical companies and doctors will want to ensure that the right patients receive the right treatment. This may include saving drug supply for extreme cases requiring hospitalization or prioritizing administration earlier in disease onset to prevent further progression. For example, if Remdesivir is successful in trials, some "antiviral experts think the drug should primarily be used for patients with more severe symptoms and those who are hospitalized—some 15% to 20% of cases," Andrew Joseph reported for STAT News. It's possible that early access may be limited.
Additionally, it's important to ensure that patients already dependent on some of these drugs to treat other conditions such as lupus and rheumatoid arthritis will still have access. Many hospitals are already rushing to order these drugs in bulk to prepare for coronavirus. As a result, some patients are already experiencing shortages for hydroxychloroquine; others are asking for extra months of prescriptions.
3. When (and if) drugs are approved, will they be affordable?
We'd expect drugs to be fairly priced during this time of crisis, and the $8.3 billion spending bill signed into law earlier this month includes a provision that when a vaccine becomes available, the government will pay a "fair and reasonable" price for it. However, the federal government does not have drug price negotiating authority and cannot mandate the price that manufacturers must charge for a drug.
It's too early to predict the price of any drugs under investigation, but the type and complexity of the molecule will usually contribute to a drug's final price. For example, novel antibody treatments (treatments derived from proteins produced by the immune system that can neutralize pathogens like coronavirus) are typically more expensive than pills. They also require special handling such as cold-chain shipping, storage, and refrigeration. This complexity might contribute to a higher price, or delayed distribution—causing the health care industry to experience additional costs in hospitalizations and makeshift treatments. Since manufacturers of existing treatments like chloroquine have already slashed their drug prices in response to coronavirus it's likely that existing products present a likely cheaper option in the short-term.
However, drug pricing advocates are proposing new-in-kind payment options to incentivize pharmaceutical manufacturers to offer lower prices for novel coronavirus drugs. Peter Bach argues that the United States should buy coronavirus vaccines, even before they are invented, in order to guarantee a good price for the government and ensure profit for manufacturers.
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These open questions will continue to shape the COVID-19 drug development conversation. For more resources on coronavirus, visit Advisory Board’s top resources for coronavirus readiness.