Drugmakers move to counteract expiring patents with new respiratory drugs

The FDA in September approved Boehringer Ingelheim’s muscarinic antagonist Spiriva Respimat as a first-in-class asthma treatment.

Recently plagued by patent expirations and generic competition, the respiratory space has found new energy through innovative beyond-the-pill partnerships. Indeed, an enhanced understanding of disease drivers continues to breathe new life — pun unabashedly intended — into a sector on the cusp of rebound

Celebrated for a slew of prosperous assets to treat asthma, COPD, and allergies, the respiratory drug business has grown up to deal with patent expirations and other changing market dynamics. To stay afloat, companies are pursuing more convenient drug-delivery options and gravitating toward unmet medical needs and niche treatment areas. Symptom-driven care is falling out of favor with lung-drug leaders increasingly interested in assigning optimal treatment approaches to patient conditions.

“Helping the respiratory community better understand the underlying biology, patient phenotypes, and new drug combinations will offer step changes in clinical outcomes for patients,” says Chris Blango, VP, U.S. medical affairs respiratory, at AstraZeneca.

A host of factors, including an aging population, rising environmental pollution, and increasing diagnosis and drug treatment, will keep the asthma and COPD markets in the green. But for the most part, patients continue to use medicines and steroids that emerged 20 years ago.

GlaxoSmithKline shares the inhaled corticosteroid and long-acting bronchodilator space with Merck’s Dulera and AstraZeneca’s Symbicort and is bracing for generic competition to Advair. GSK’s respiratory franchise accounts for 40% of the company’s sales; Advair did its part by pulling in $8 billion annually at its peak.

While some analysts have questioned GSK’s financial stability, SVP, primary care Deborah Waterhouse insists that “sales contributions from the medicines we’ve launched over the past three and a half years are now exceeding what we’re losing on Advair.” All eyes are on Advair’s successors, the once-daily combos Breo and Anoro, to make headway in the most profitable asthma drug class.

Boehringer Ingelheim’s muscarinic antagonist Spiriva Respimat (tiotropium bromide) was approved as a first-in-class asthma treatment. The asset will expand the firm’s presence in the respiratory space, but is unlikely to draw as much revenue as it has within the COPD population.

On the other hand, experts contend that generic erosion is unlikely to be a factor for inhaled products. Providers and patients alike will be hesitant to embrace a new device, plus the pricing profile will not be attractive enough to prompt a switch.

While loyalty runs deep on the consumer side, inhalation therapies add challenges for developers. Respiratory leaders must contend with balancing drug and device.

“With inhalation therapies, the delivery device is as important as the drug being delivered,” points out Matt Hartney, EVP, respiratory brands, Triple Threat Communications.

Corbus Pharmaceuticals CEO Yuval Cohen underlines the benefits of developing a pill for diseases like asthma and COPD, but says that the R&D is not there yet. “The handheld pump will be with us for a long time,” he stresses.

PRECISION MEDICINE RISES

Precision therapies are belatedly making their way onto the respiratory scene as firms increasingly break free of the one-size-fits-all model for common conditions. In the U.S. alone, nearly 25 million people suffer from asthma.

“For how common it is, we know surprisingly little about the biology behind asthma,” says Dr. Joe Arron, director of immunology discovery at Genentech. “But that’s starting to change.”

Pharma is increasingly aware that asthma presents in different forms, requiring the use of biomarkers to individualize drug targets. To that end, Genentech is taking a cue from its own oncology enterprise to pursue asthma and COPD genetic profiles. The company has entered into a license agreement for Amgen’s Phase II-ready anti-ST2 antibody AMG 282.

Despite advances in asthma and COPD, unmet needs loom large particularly for patients at the severe end of the spectrum.

“The drugs are limited and can’t always control symptoms,” explains Beran Rose, VP of marketing and business development for Pulmonx, a firm developing diagnostic and therapeutic tools for severe COPD.

Market forces set the stage for the timely arrival of biologics, an area first explored by Genentech with its 2003 approval of Xolair (omalizumab). Arron believes the tide has turned with the development of IL5 and IL13 inhibitors, where multiple therapeutic candidates have shown enhanced efficacy in type 2-high or eosinophilic asthma. Genentech is conducting Phase III studies of lebrikizumab in severe asthma and Phase II studies in IPF, COPD, and severe atopic dermatitis.

Datamonitor Healthcare predicts that four biologics — GSK’s Nucala, Teva’s Cinquil, AstraZeneca’s benralizumab, and lebrikizumab — will drive growth in the asthma market through 2024. Although prescription numbers will remain low due to a small target population, extreme price tags will translate into substantial revenue.

Keep reading for more on the pipeline for drugs to treat COPD and idiopathic pulmonary fibrosis as well as beyond-the-pill initiatives for respiratory drugs.

BEYOND ASTHMA

Vertex now markets two treatments for cystic fibrosis: Kalydeco and Orkambi, which was approved last year.

While asthma may appear to be hogging the pathogenetic spotlight, targeted therapies are on tap for COPD, idiopathic pulmonary fibrosis, and others. The issue, so far, has been an inability to define the distinct patient subsets that will benefit from new therapies. AstraZeneca’s PT003 is awaiting FDA approval as the first LAMA/LABA product available in a single pressurized metered dose inhaler (pMDI) for the treatment of COPD, while triple therapy PT010 is in Phase III trials. Benralizumab’s phase III results and regulatory filing in COPD are expected in 2018.

Novartis is juggling a pair of COPD contenders: NVA237, a bronchodilator sold as Seebri Breezhaler in Europe, and QVA-149, which combines NVA-237’s active ingredient with approved Onbrez. GSK awaits an FDA nod for Breo/Incruse.

Trinity Partners’ Ryan Million notes a major trend in firms developing treatments for orphan and specialty respiratory diseases, with the most activity heating up on the cystic fibrosis front. Vertex’s Kalydeco (ivacaftor) targets the defective cystic fibrosis transmembrane conductance regulator protein, the underlying cause of CF. Vertex’s second CFTR modulator, Orkambi (lumacaftor/ivacaftor), was approved last summer.

Corbus’s oral anti-inflammatory Resunab entered Phase II studies for CF, and Galapagos NV and partner AbbVie announced plans to develop a triple CFTR combination therapy. Translarna (ataluren) is in Phase III studies for CF caused by a nonsense mutation (nmCF), which affects about 10% of the population.

“We’ve aimed the development at a specific segment of the population,” says Mark Rothera, CCO at PTC Therapeutics. “You could argue that it’s an orphan of an orphan.”

In nmCF, the CFTR protein isn’t fully produced at the cellular level. Translarna aims to enable the development of full-length functional protein. “The drug treats the underlying cause of the disease,” shares Rothera. “It’s the ultimate personalized medicine.”

Datamonitor predicts that, driven by an increase in diagnoses and continued uptake of Roche/Genentech’s Esbriet (pirfenidone) and Boehringer Ingelheim’s Ofev (nintedanib), the market will expand through 2024 for IPF. Trinity’s Million points to remarkable improvements in pulmonary arterial hypertension outcomes, suggesting that other orphan indications might gain knowledge from that particular model. Approved in late 2015, Actelion Pharmaceuticals’ Uptravi (selexipag) is the latest entrant in the PAH arena. Though the sector is pursuing an innovation agenda, available drugs fail to meet all PAH needs.

BEYOND THE PILL

GlaxoSmithKline partnered with Propeller Health to incorporate its sensor technology (pictured) in Ellipta inhalers.

In hot pursuit of improved outcomes, better adherence rates, and patient conveniences, respiratory drug developers are entertaining partnerships with medical device and technology firms. Experts expect the space to gain momentum in sophistication and relevance, noting an uptick in devices that track patient information.

Accordingly, GlaxoSmithKline is entertaining collaborations to incorporate sensor technology into its R&D plan. Most recently, Propeller Health has agreed to develop and manufacture a certified sensor for the Ellipta inhaler for use in clinical studies. The goal, according to Waterhouse, is “to more precisely correlate adherence with safety, efficacy, and economic outcomes.”

Teva and Gecko Health Innovations are taking a similar path. Teva acquired the rights to the company’s CareTRx technology, a cloud-based solution to simplify chronic respiratory disease management through remote monitoring.

Hartney feels the respiratory market’s foray into technology partnerships parallels the evolution of glucose monitors.

“Technological advances have led to automated devices that provide an important link between patient and healthcare provider to improve care,” he explains. Along those lines, AstraZeneca’s novel Aerosphere Co-Suspension Technology platform holds hope of improving the delivery of PT003 and similar treatments into the lungs by letting multiple molecules exist in a single pMDI.

By design, the device industry lends itself to swift innovation, says Larry Mastrovich, Breathe Technologies’ president and CEO. “Prescription drugs are a critical element of respiratory therapy, but it takes significant investment to earn FDA approval,” he says. “In contrast, the device industry can typically bring a technology to market quickly by establishing clinical equivalence to an existing device.”

Mastrovich hopes the promise of improved outcomes will encourage device and drugmakers to collaborate on ongoing clinical postmarketing studies. “Our primary mutual goal is to demonstrate that the upfront costs of a medical device or drug are frequently far exceeded by long-term savings realized in the overall cost of care,” Mastrovich says.

From the April 01, 2016 Issue of MM+M - Medical Marketing and Media