Fueled by precision medicine, drugmakers delve deeper in autoimmune diseases

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The autoimmune drug sector is flirting with a sudden growth spurt as scientists continue to zero in on the structure and function of the immune system. R&D efforts are expanding their once-narrow focus on rheumatoid arthritis, psoriasis, and other “windfall” diseases to embrace populations with lupus, Celiac disease, and some 80 other autoimmune conditions.

With autoimmune disorders, the body's white blood cells sit down on the job. Instead of fending off bacteria, viruses, and other foreign invaders, the cells ravage the host's own tissues and organs, leading to a cascade of events, among them exacerbated inflammation and cell destruction.

The sector is mimicking an industrywide push toward precision medicine — and the timing couldn't be better, as experts note a marked increase in autoimmunity.

See also: With competition lurking, Eli Lilly's baricitinib must show unparalled efficacy

“Autoimmune therapeutics are moving toward highly specific targeted therapies and aim to be more effective with good safety profiles,” explains John Bradley, MD, senior medical fellow of U.S. medical affairs, rheumatology, at Eli Lilly. “It's a theme that runs across the whole industry.”

AbelsonTaylor VP and account director Mark Finn notes that the latest research efforts include an intense focus on biomarker imaging and combination therapy to personalize therapies at specific points across the patient's inflammation spectrum.

“These advances may make it possible for more patients with autoimmune diseases to obtain clinical remission,” he says.

Digitas Health LifeBrands' VP, group director, science and medicine Lee Fraser, PhD, on the other hand, cautions that answers to the question of remission vis-à-vis disease control remain elusive.

“Current therapies help in the chronic management of these diseases,” he says. “However, the true goal remains induction of immune tolerance.”

Indeed, innovators are devoting much of their energy to attempts to improve disease response and patient comfort.

“Patient and provider communities await therapies that address life-threatening disease risks and are less toxic,” notes Gil Bashe, managing partner, Finn Partners.

But drug innovation is only half the battle. Today's marketers must attract the attention of providers, patients, and consumers. “Breaking through promotional noise is daunting,” Finn acknowledges.

At the same time, prices are going haywire in the category. Formulary position, innovative pricing approaches, and comparative data for generics and biosimilars will top marketers' lists of challenges.

“Payers will have a significant voice in what therapies providers select and patients use,” Bashe says. “Unless its price matches market growth potential, a drug touting ease of use is no longer sufficient to gain market attention.”

THE STATE OF RA

Owning the distinction of most common autoimmune disease flag, rheumatoid arthritis has garnered quite a bit of pharma attention in recent years. In fact, AbbVie's Humira (adalimumab) ranked second among the most advertised drugs of 2014, with $259 million in annual ad spend. Decision Resources Group expects the RA market to continue to enjoy modest growth, with projected sales of $15.2 billion in 2021 in the eight major markets.

DMARDs, including methotrexate, have long held the first-line treatment spot for RA. While many pundits say that it's unlikely a newcomer will supersede this class of drugs, any number of companies covet its command of prescription pads. “The first treatment post-DMARD, be it biologic or non-biologic, will be the battleground,” Fraser says.

Physicians turn to biologics when conventional DMARDs fail to elicit the proper response or ignite an unmanageable side-effect profile. Pfizer/Amgen's Enbrel (etanercept) and Humira are counted among the widely prescribed anti-TNF class. Bristol-Myers Squibb's Orencia (abatacept) aims to block the body's T cells, while Genentech's Rituximab zeros in on certain B cells.

See also: Top 20 autoimmune products in 2015

Pfizer's Xeljanz is currently alone on the janus kinase ( JAK) inhibitor island for the treatment of RA, but several ships are approaching those shores. In particular, Lilly's baricitinib is on course to enter with a splash later this year.

While promising, few industry analysts have faith in JAK inhibitors' ability to soar to the level of market dominators Humira, Remicade, and Enbrel. Unlike biologics that block pro-inflammatory cytokines from outside the cells, JAK inhibitors work inside cells to interrupt the signaling pathway.

Meanwhile, AbbVie is staring down the biggest patent loss in the history of the drug industry. It is doing everything in its power both to fend off the imminent event and to protect mega-blockbuster Humira from biosimilar competition.


IMPACT OF BIOSIMILARS

The U.S. drug market recently welcomed its second biosimilar approval. CT-P13, Pfizer/Celltrion's biosimilar of J&J's Remicade (infliximab), is the first impersonator monoclonal antibody to be launched in the country. The FDA has also accepted Amgen's application for adalimumab biosimilar ABP 501. In a recent study, the copycat improved symptoms at a rate similar to Humira and had a comparable safety profile.

Payers, providers, and patients are all paying close attention to the promise of biosimilars — and especially their potential cost savings. Payers may become the biggest biosimilar boosters if the copycats prove themselves. According to Finn, the market isn't willing to trade safety or efficacy for a price reduction.

If biosimilar performance can closely match that of originator brands, Finn predicts comfort with the newer products will increase and power may quickly shift to the payers. It's widely known that the biologic/biosimilar relationship will not produce the same reduction in costs as small molecule/generic accord — but even small price decreases can have a large payer effect.

COMPETITION HEATING UP AROUND COSENTYX

Novartis's domination of the psoriasis market in the wake of last year's approval of Cosentyx may not hold for long. Numerous developers are aiming for the throne — notably Lilly, with its injectable ixekizumab. The treatment, which blocks a cytokine called interleukin-17A, topped placebo and Enbrel in a Phase III study.

Competition is heating up in the interleukin antibody field as well, with Merck and Johnson & Johnson present in late-stage trials with similar therapies. Plus Valeant Pharmaceuticals recently picked up an IL-17A treatment from AstraZeneca.

Meanwhile, Novartis nabbed two new indications to treat adult patients with active ankylosing spondylitis and active psoriatic arthritis earlier this year. “Novartis's head start is no guarantee of continued market success,” Bashe stresses. “If data and price are compelling, this category can soon see a new market leader.”

AUTOIMMUNE DEVELOPMENT MOVES TO THE MARGINS

Moving forward, many believe the autoimmune segment will be more about underdog diseases — the likes of lupus and IBD — and less about those that have had their time at the top. “If the door opens to conditions with few therapeutic options, payers and providers will open their minds to prompt access,” Bashe says.

Roche/Genentech's ocrelizumab, having received FDA breakthrough designation for primary-progressive MS, is sitting pretty in the MS space. By selectively targeting CD20-postive B cells, the mon­o­clonal antibody is the first investigational medicine to show positive results in both relapsing and primary progressive forms of the illness.

Patients with relapsing MS and their doctors need “new medicines that offer the potential to effectively control disease activity and MS progression,” says Genentech-Roche's principal medical director and neurologist Dr. Peter Chin. Although 13 drugs, including Biogen's Tecfidera and Teva's Copaxone, have the FDA seal of approval for treating relapsing-remitting MS, none has proved efficacious in primary-progressive MS.

Following declining sales in 2015, Tecfidera is expected to right itself this year, with ana­lysts predicting about $3.9 billion in sales. Biogen plans to present data from the Phase II trial of its other MS weapon in development, anti-LINGO-1.

For the treatment of osteoporosis, Eli Lilly's Forteo may need to make room for abaloparatide, another once-daily injectable Radius is studying. Amgen/UCB is also lining up with its investigational monoclonal antibody romosozumab, a once-monthly injection. Noah Pines, president of ThinkGen, says romosozumab exhibited relatively high clinical fracture reduction rates in its Phase III FRAME trial.

Critics are watching romosozumab warily, mainly for missing a secondary endpoint in the FRAME study. “Doctors may ask questions when looking specifically at its non-vertebral fracture data and changes in wrist BMD, as well as at the few cases of jaw necrosis and atypical fracture,” Pines explains.

Following dry spells, things appear to be looking up on the lupus and Celiac disease R&D front. Promising research efforts for lupus include Astra­Zeneca's anifrolumbab, EMD Serono's recombinant fusion protein atacicept, and Pfizer's anti-IL-6 antibody. The patient need for these diseases is very high, while the bar to success has been set relatively low, Bashe explains. “If the introduction price of a new lupus treatment considers the market need, clinical benefit, and societal sensitivity, then blockbuster status is possible.”

Although 83% of those who suffer from Celiac disease re­main undiagnosed, the condition has attracted significant research efforts. Celimmune licensed a Phase II anti-IL-15 monoclonal antibody from Amgen, and Alba Therapeutics is studying larazotide acetate. “The market for these potential entrants is substantial,” Finn says. “If they can tap the undiagnosed patient market, the success of these therapies may skyrocket.”

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