Forecasting the pain management market
Angelo DePalma outlines the prospects for the global market for pain management pharmaceuticals and devices
Current pain management strategies are clearly inadequate for millions of individuals suffering from pain related to cancer, lingering injuries, and other ailments.
The propensity of opioids, by far the most-prescribed agents for moderate to severe pain, to induce habituation and to tempt misuse underscores the need for safe, non-addictive pain medicines.
As these are several years from entering the marketplace, developers seek alternate strategies for meeting a poorly served medical need.
Managing moderate to severe pain is big business.
BCC estimated the global market for pain management pharmaceuticals and devices at $19.1 billion in 2008 and predicted 11.5% compound annual growth through 2013.
BCC estimates that the pharmaceutical component, comprising approximately 90% of sales, will reach $32.8 billion by 2013.
Opioids are by far the most-prescribed pain agents.
According to 2008 data from IMS Health, opioids took second place to cholesterol regulators in total scripts at more than 200 million, but were only fifteenth in sales.
With their ready availability, low price (even on illegal markets), and ability to induce euphoria, the prescription opiate trade is open to abuse and such enabling illegalities as theft, diversion, counterfeiting, and doctor shopping.
The US Centers for Disease Control and Prevention reports that fatal overdoses from prescription opioids more than tripled between 1999 and 2006 (the last year for which reliable data are available), from 4,000 to nearly 14,000.
Preferred agents of abuse were oxycodone- and hydrocodone-containing formulations, with misuse of older drugs like methadone, morphine, and hydromorphone lagging but still troublesome.
Policymakers were quick to associate the dramatic rise in fatalities with the proliferation of formulations of the two preferred opioids.
As a result of this conclusion, the annual budget of the US Drug Enforcement Agency grew from $1.5 billion in 2000 to $2.6 billion in 2009.
And with that growth, some critics say, has come an increase in the heavy-handedness of both DEA and local authorities.
Avoiding abuse
Forty US states monitor painkiller use but the numbers of potential abusers overwhelms enforcement.
Customers, whether legitimate or not, circumvent the law by traveling to more lenient jurisdictions, sometimes renting buses specifically for that purpose.
Regulators have attempted to stem the tide of illegal opiate dealing through regulation.
The FDA has in the past relied on letter-writing campaigns to opioid drug manufacturers, the worst consequence of which was a “Black Box” warning.
Isolated products, like the buccal fentanyl product Onsolis (Meda Pharmaceuticals), a fast-acting analgesic with very high abuse potential, were singled out for a risk evaluation and mitigation strategy (REMS).
A relatively late-vintage addition to the regulatory lexicon, REMS are meant to ensure that a drug’s benefits outweigh its risks within real-world prescribing and use.
Most REMS incorporate extended warnings and patient/caregiver education, but the designation may (as in the case of Onsolis) include restricting the therapeutic indication, who may prescribe the drug, and how it is distributed.
By July 2010, the agency, tiring of patchwork regulation, proposed a class REMS that covered both long- and short-acting opioid drugs.
The FDA is now weighing stakeholder input on the new regulations. (For more on REMS, see ‘Market access: How to get REMS right’ and ‘The Impact of REMS on Market Access’.)
Opioid pain agents have been undone by their own efficacy and market success.
Most of the 50 pain products approved by the FDA between 1980 and 2000 were either opioids or non-steroidal anti-inflammatory drugs (NSAIDs).
By the mid-2000s, it was apparent that top pharmaceutical firms were uninterested in developing medicines to treat serious pain.
The predominant philosophy was in no small way affected by the controversies surrounding non-opioid drugs (e.g. non-addictive NSAIDS) and what was perceived as a gathering storm for agents with abuse potential.
Still, there is reason to be optimistic that drug developers will achieve the proper balance of efficacy and low abuse potential.
Market outlook
In its 2009 study, The Pain Management Market Outlook to 2014, Business Insights lists several novel classes of pain drugs, from which we can expect to see some marketed products within a decade.
These include the exotic-sounding bradykinin antagonists, mPGES-1 inhibitors, glutamate receptor antagonists, substance P and neurokinin receptor antagonists, P2X2 neuron receptor antagonists, and ion channel agents.
The sole marketed compound from this group, the cone shell toxin Prialt® (Azur Pharma), has experienced less-than impressive sales ($20 million in 2009).
Similarly the most notable recent US pain approval, Nucynta™ (tapentadol; Johnson & Johnson), a non-opioid, was approved in late 2008 but was classified as a controlled substance in early 2009.
Part of the problem is how we define abuse.
Many professionals, particularly law enforcement, confuse dependence with addiction.
“Patients who depend on insulin or blood pressure medicines are not considered addicts,” notes Edgar Adams, Sc.D., executive director for epidemiology at Covance, “but unfortunately, patients taking opioid analgesics often are.”
Despite the US Food and Drug Administration’s desire for uniform regulation of opioids, there remains a good deal of uncertainty if the FDA will work with controlled substances, says Princeton, New Jersey-based independent consultant Nassim Zaagoub, “particularly for products indicated to treat moderate to severe pain.”
Zaagoub has recently completed a privately sponsored study on pain management.
Yet, he says that regulators, particularly the FDA, are becoming “overly cautious to avoid mistakes of the past” when pain medicines, particularly (although not limited to opioids), were less tightly controlled.
If history is any judge, then seemingly burdensome regulation may actually help the fraternity of specialty pain drug manufacturers.
Zaagoub notes that Purdue Pharma’s regulatory problems during the late 2000s may have negatively affected sales of all oxycodone medicines.
“The sales slump in 2008 coincided with Purdue’s troubles,” he says.
But after the company and agency made peace, oxycodone sales began rising again.
“And it looks like the rise is occurring at the expense of hydrocodone,” Zaagoub concludes.
Predicting sales
Overall, his study suggested that sales increases for all opioid painkillers were slowing down, possibly due to enforcement or demographic changes.
In its 2010 report, Pipeline Insight: Moderate-to-Severe Acute Pain—Positive Outlook for Opioid-sparing Analgesics, Datamonitor analyzed markets and pipelines for moderate to severe pain in seven jurisdictions (US, Japan, France, Germany, Italy, Spain, and the UK).
Basing its analysis on data obtained from IMS Health in March 2010, Datamonitor reported that sales of drugs for moderate-to-severe pain in these seven markets reached $3.9 billion in 2009.
Growth, at a CAGR of 4.6% over the coming decade, will drive sales to $6.1 billion by 2019.
Datamonitor predicts that by 2019, current development-stage drugs will account for $1.5 billion in sales, or about one-fourth of the acute pain market.
However, as Trung Huynh, a healthcare analyst with the firm, notes, “current pipelines lack innovation and are comprised largely of reformulations of established molecules.”
Reformulation and/or combination with new delivery methods has long been viewed, by “specialty pharmas,” particularly those developing acute pain medicines, as a relatively risk-free strategy for new product introduction.
This trend, which has dominated the pain marketplace for two decades, will remain vibrant until new agents reach the marketplace.
Since the molecules enjoy a long history of legacy use, regulators are familiar with them and have lessened requirements for clinical testing.
Reformulated products benefit from expedited regulatory approval via the FDA’s 505(b)(2) designation.
Reformulated opioids are touted for any of several benefits that include more rapid onset of action, greater convenience/compliance, and dosing formats that are difficult to tamper with.
In the US, the FDA has come down hard on firms claiming reduced abuse potential, so developers must talk around that benefit.
But introducing such products is by no means risk-free.
Developers will come under increasing scrutiny to provide tangible benefits relative to the state of the art, either in improved efficacy, fewer side effects, or lower abuse potential.
Another consideration, in the US, Canada, and Europe, is reimbursement in the face of generic competition. (For more on generics, see ‘Forecasting for generic erosion rates’.)
In addition to the opioids and non-opioid painkillers, the so-called opioid-sparing analgesics will gain in importance as the marketplace awaits the next crop of new molecular entity pain agents.
Opioid-sparing drugs include the NSAIDs such as celecoxib (Celebrex, Pfizer) and agents such as Lyrica (pregabalin, Pfizer), Ereska (intranasal ketamine, Javelin Pharmaceuticals), Exparel (bupivacaine, Pacira Pharmaceuticals), and Posidur (bupivacaine, Nycomed/Durect).
Opioid-sparing strategies involve using the non-opioid drug for baseline pain, and an appropriate opioid for breakthrough episodes.
Opioid-sparing drugs are co-administered with opioid medicines that treat severe pain rapidly and effectively, but with a pharmacokinetic profile unsuitable for abuse.
Recent advances in the formulation of fentanyl, as nasal or sublingual nasal sprays, dissolving buccal films or lozenges, and metered inhalers used side-by-side with NSAIDs are examples of the emerging intersection of safe, effective opioids and opioid-sparing agents.
Markets are small today, in the tens of millions of dollars per year, but Datamonitor predicts that rapidly acting fentanyl-based pain medicines will enjoy rapid growth over the next decade, garnering combined revues of $600 million by 2019.
For more on forecasting, join the sector’s other key players atForecasting Excellence USA on October 4-6 in Boston.
For an overview of eyeforpharma’s forecasting coverage, see ‘Highlights from eyeforpharma’s Forecasting coverage’.
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