With less than 14% of Phase I to III drug candidates winning FDA approval, unforeseen roadblocks can derail even the most promising clinical research programs. But with a steadfast attitude and transparent messaging, biopharma companies can recover from unexpected obstacles — and set themselves up to thrive.
That’s a feat demonstrated by three mid- to late-stage candidates currently working their way through clinical trials. The first comes from Solid Biosciences, a company with a single-minded focus on Duchenne muscular dystrophy. Solid’s gene therapy candidate, SGT-001, hit a rough patch earlier this year after a serious adverse event prompted the FDA to place a clinical hold on the trial. But the company developed a contingency plan to ensure patient safety, a move that paid off when the FDA lifted the clinical hold only three months later.
Meanwhile, Celgene’s approval application for its multiple sclerosis candidate, ozanimod, was met with a surprise refuse-to-file letter in February, prompting the company to reassess its application materials.
Finally, Alexion stumbled into a Wall Street squabble over the efficacy of its paroxysmal nocturnal hemoglobinuria drug ravulizumab, with some investors questioning whether the drug marks an improvement over the company’s existing blockbuster, Soliris. Alexion has remained steadfast in its assertion ravulizumab will benefit patients because of its superior dosing schedule — a message that’s resonating with physicians and patients.
Solid Biosciences, Phase I/II
Indication: Duchenne muscular dystrophy
Catalyst: SGT-001 is an investigational gene therapy for Duchenne muscular dystrophy (DMD). But the FDA placed a hold on the IGNITE DMD Phase I/II trial after one patient experienced a serious adverse event in the form of reduced platelet count. Solid promptly promised to monitor patients and treat them for low platelet count should the same problem crop up again.
Those steps were enough for the FDA, which lifted IGNITE DMD’s clinical hold after just three months. Despite the adverse event, enthusiasm remains high for this candidate, notes inThought Research medical adviser Dr. Leon Henderson-MacLennan.
Solid’s chief scientific officer Dr. Carl Morris says the company hopes to have interim data available in the second half of 2019. “Right now, there is no good treatment for the majority of patients with Duchenne muscular dystrophy. It is 100% fatal,” he notes.
Competitive landscape: Solid isn’t the only company advancing a gene therapy for DMD. Both Sarepta Therapeutics and Pfizer are moving ahead with their own candidates, which are similar to SGT-001. Despite the competition, Morris welcomes the arrival of other new treatment options for this incurable disease. “We are excited by the progress,” he says.
Henderson-MacLennan believes it’s too soon to predict which candidate will make it to market first. In terms of the efficacy and safety profiles, he notes, “The devil is going to be in the details of the clinical trials that are ongoing.”
Messaging strategy: Because SGT-001 is a gene therapy, it could be argued that patients who are treated successfully will be “cured.” However, Morris doesn’t necessarily see it that way. “It’s a treatment,” he explains. “We hope it will slow or stop the continued progression of the disease. But ‘cure’ means you come back to a normal phenotype, and we don’t think that’s possible.”
According to Henderson-MacLennan, it’s smart for Solid to take a conservative approach — which is rare in the splashy world of gene therapies.
That isn’t to say Solid won’t eventually earn those bragging rights.
“Current non-steroidal therapy for DMD only addresses a small subset of patients with a certain mutation. SGT-001 will be the first therapy in the space that will work regardless of mutation status,” says Heartbeat SVP, medical director Madhuri Fletcher. “Ideal messaging will focus on treating all, regardless of mutation status or disease stage.”
Marketing strategy: Although it’s early days for SGT-001, Solid and its competitors are likely to follow a relatively straightforward marketing plan for rare diseases with high unmet need. “It will be important to identify families early. Solid will need to partner with the strong support communities in the DMD space and integrate with the multidisciplinary approach to DMD management,” explains Fletcher. “There will also be an opportunity to demonstrate commitment to the DMD community by coming in at a more reasonable price than the controversially expensive in-market competitor.”
Advocacy groups want transparency, Morris adds. “They want to help educate patients and the community about what gene therapy can provide and what it can’t.”
Celgene, Phase III
Indication: Multiple sclerosis
Catalyst: Ozanimod, which has been tested in two Phase III trials for relapsing multiple sclerosis, was assumed to be a sure-fire blockbuster — that is, until the FDA issued a surprise refuse-to-file letter in February, sending the company’s shares tumbling 9%.
But the regulatory delay won’t crush ozanimod’s blockbuster potential, according to inThought Research president Ben Weintraub. “It was a business setback, but I didn’t see anything concerning about the way the drug works,” he explains.
To that end, Celgene clarified it won’t have to conduct any additional in-human studies and plans to refile early next year. This puts ozanimod back on the map for a tentative launch in 2020.
Competitive landscape: Celgene is seeking approval for relapsing MS based on Phase III data that demonstrated ozanimod’s superiority to Biogen’s Avonex (interferon beta-1a). Although Celgene is back on track to win approval, there’s already lots of competition in the MS market, including Avonex and Roche’s Ocrevus (ocrelizumab).
Celgene is “on the clock to get it out there before Gilenya [fingolimod] goes generic,” Weintraub says.
Considering the market competition, ozanimod’s real potential may lie in other indications. Weintraub notes the drug is being tested in ulcerative colitis and Crohn’s disease, where few oral treatment options exist.
Messaging strategy: Celgene shouldn’t worry about the FDA’s refuse-to-file when it comes to messaging the drug, according to Strategic Marketing Solutions principal Richard Meyer. Instead, patients and physicians will be focused on the drug’s side-effect profile. MS patients are extremely active on social media, he notes, so Celgene will have to produce data that convinces them and physicians ozanimod dramatically improves quality of life.
“That could be difficult,” he adds. “It’s kind of hard to be the new kid on the block.”
Marketing strategy: Meyer believes to gain an edge, Celgene should price its drug at or below the wholesale cost of its competitors. It also makes sense for the brand team to “plunge into social media.”
But TV is still crucial, even in today’s digital world. “The number one way people find out about new products is still a TV ad,” Meyer continues. “I would go on TV as heavy as I could, then measure the awareness among MS patients. Once you get awareness to a certain level, you start talking about advantages over the competition.”
Alexion, Phase III
Indication: Paroxysmal nocturnal hemoglobinuria
Catalyst: Ravulizumab, also called ALXN1210, is Alexion’s next-gen treatment for paroxysmal nocturnal hemoglobinuria (PNH). The drug is slated to replace Alexion’s existing blockbuster, Soliris. In two Phase III studies, treatment with weight-based ravulizumab proved non-inferior to Soliris across 11 primary and secondary endpoints. But the drug’s key selling point is its dosing schedule, with Soliris requiring dosing every two weeks and ravulizumab every two months. Normally the FDA takes an entire year to approve applications, but Alexion used one of its priority review vouchers, which is likely to speed up the review process by at least four months.
Competitive landscape: Ravulizumab isn’t facing any steep competition, Henderson-MacLennan notes. Heartbeat VP, strategy Simon Beins adds, “Ravulizumab, like Alexion’s 11-year-old Soliris, have a lot in common: They share a mechanism of action; their efficacy results, so far, look similar; and they have no competition from any other drugmaker.”
Messaging strategy: According to Beins, ravulizumab’s messaging priority will be clear: convenience. “PNH usually strikes younger adults at prime working and child-raising ages, so a less disruptive administration schedule will be compelling,” he explains. Because Soliris has a black box warning, ravulizumab is likely to have one, too. “The chance of meningococcal infections is high. So, Alexion will have to demonstrate there are no surprises hidden in its safety profile,” Beins continues.
Marketing strategy: Considering the high price tag for Soliris — around half a million dollars per year — Alexion’s marketing strategy for ravulizumab could hinge on the price execs decide to set. “Given ravulizumab will likely cannibalize much of Soliris’ business, we’ll see exactly how Alexion balances its reputation [it has faced criticism and legal action over Soliris’ price tag] with its bottom line,” Beins says.
In the wake of Soliris’ patient support program, the team marketing ravulizumab will benefit from the learnings and infrastructure Alexion has built interacting with PNH patients. “This high-touch approach also extends to HCPs,” Beins adds, noting PNH is so rare, many have never seen a case of it.