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Elaine Quilici is Pharmaceutical Executive's Senior Editor. Email her at firstname.lastname@example.org
Amid the noteworthy product launches profiled this year by Pharm Exec are four more therapy trailblazers worth highlighting.
Amid the noteworthy product launches profiled this year by Pharm Exec are four more new therapies worth highlighting. Two drugs, Vitrakvi and Luxturna, demonstrated novel applications in gene therapy. Both use the technology to treat rare diseases: Vitrakvi targets cancerous tumors based on type rather than location, and Luxturna can prevent blindness in people with inherited retinal disease.
Galafold addresses another rare, inherited condition, Fabry disease, representing the first new treatment option in 15 years for the disease. Rheumatoid arthritis drug Olumiant also has an interesting debut story. Despite safety concerns, it broke into a well-established therapeutic market and is holding steady.
All four of these products demonstrate important innovation, and the industry can learn from their trailblazing. Here’s a closer look at each.
Bayer and Loxo Oncology hit big in late 2018 with the first-of-its-kind approval of Vitrakvi (larotrectinib), which targets the genetic makeup of a tumor rather than where it originated in the body. About a year earlier, the two companies entered into a partnership to develop and commercialize the drug. Despite the $8 billion acquisition of Loxo by Eli Lilly in February, Bayer retained exclusive licensing rights for Vitrakvi in the US. The treatment, which had received breakthrough therapy and orphan drug designations, priority review, and accelerated approval from FDA, took less than four years to go from its first patient trial to approval. Analysts predict Vitrakvi’s annual sales will surpass $1 billion by 2024.
Vitrakvi is indicated for adults and children who have solid tumors with rare neurotrophic receptor tyrosine kinase (NTRK) gene fusion, which supports the growth of tumors. It is the first drug to receive initial FDA approval to treat cancers that express this specific mutation. One limitation, however, is identifying people with the condition. There must be the presence of NTRK gene fusion in patients’ tumor specimens in order to receive Vitrakvi. While there is no current FDA-approved test for detecting this, Loxo is partnering with Illumina to develop a multi-gene next-generation sequencing diagnostic.
Because it targets a rare genetic mutation in the cancer space, the cost of Vitrakvi is high. Twice-daily capsules possess a list price of $393,600 per year, while a liquid formulation costs $132,000. Bayer notes, however, that with insurance coverage, monthly out-of-pocket costs for most patients should be $20 or less. In addition, Bayer’s Vitrakvi Commitment Program promises payers, third-party payers, and patients a refund if patients demonstrate no clinical benefit within the first 90 days of treatment.
Bayer may not be the only player in the game soon. Roche’s NTRK fusion fighter Rozlytrek (entrectinib) won FDA priority review in February. And in June, Japan’s Ministry of Health, Labour and Welfare approved the potential rival.
FDA’s approval of Spark Therapeutics’ Luxturna (voretigene neparvovec-rzyl) in December 2017 was a milestone. It marked the first FDA-approved gene therapy for a genetic disease-in this case, indicated for children and adults with inherited retinal dystrophy due to RPE65 gene mutations. Luxturna was developed to restore vision and prevent blindness for these patients. The injection delivers a functional copy of the mutated RPE65 gene directly to retinal cells using an adeno-associated virus (AAV).
Upon Luxturna’s approval, Spark, currently in an extended takeover bid by Roche, faced supply chain challenges in producing a one-time treatment for an ultra-rare disease. A typical delivery approach would not work. Because gene therapies are temperature sensitive, just-in-time delivery is required. The drug also needs to be prepared just before administration, so training pharmacists, surgeons, and staff is necessary. With so few treatment centers and such specific requirements for administration, each Luxturna recipient demands individual attention. All of these logistics had to be defined and molded into a brand-new supply chain model.
In addition, Spark needed to develop a pricing structure that worked for a one-time gene therapy, an issue not without controversy for this and other since-approved curative therapies. The company decided on an outcomes-based model for Luxturna with an upfront cost of $425,000 per eye. Including ongoing case management after treatment, the pricing, Spark says, provides value to payers and reasonable access to patients. The initial setup required working closely with stakeholders and insurers to educate them in the new process. Within nine months of Luxturna’s launch, Spark established 85% coverage from major insurers and 50% coverage from public payers.
Luxturna was approved in Europe in November 2018 (under a licensing agreement, Novartis commercializes the product in the EU). Spark reported $64.7 million in total revenue for 2018, of which $27 million was attributed to net US product sales of Luxturna. Some analysts, according to published reports, see the drug generating more than $300 million by 2022, in line with the overall growing gene therapy market.
Roche initially launched its bid for Spark in February and, despite government delays, hopes to finalize the deal by April 2020. The pharma giant anticipates that Luxturna and a pipeline of other gene-based medicines will facilitate the company’s expansion into the field.
Good things don’t always come easy. That seemed to be the theme of Amicus Therapeutics’ Galafold (migalastat). Approved in August 2018, it took more than a decade to bring the company’s first product to market. In addition, the drug has a complicated dosing schedule that could create compliance issues. But for adults with Fabry disease, a condition caused by mutations of the GLA gene that can damage tissues and organs, Galafold was a welcomed treatment alternative. While traditional drugs for Fabry disease rely on enzyme replacement, Galafold boosts the activity of the deficient enzyme. As a capsule, it is also easier to administer than the infusion delivery required by many competitors in the market.
Galafold received orphan drug designation in 2004. In 2012, clinical testing failed and sent Amicus back to the drawing board. Galafold was rejected for approval by FDA in 2016, citing the need for more long-term data. The treatment did get EU clearance that same year, but it wasn’t until Scott Gottlieb took over as FDA commissioner in 2017 that the agency eased up on its demands and granted Galafold priority review. It was then given accelerated approval in the US. Galafold is also approved in Canada, Switzerland, Israel, Australia, and South Korea.
Amicus priced Galafold at $315,000 per year, which is below the average cost of other Fabry disease treatments. The NJ-based biotech favored the set pricing over an outcomes-based model, because it believes it would be difficult to assess outcomes. The Amicus Assist program provides support services for patient access to Galafold, and the company has pledged publicly to keep price increases no more than the rise of inflation.
Though available orally, there are many stipulations on how Galafold is administered. Patients must take one capsule once, every other day at the same time of day. This needs to be done on an empty stomach (no food for at least two hours before and after). A missed dose must be taken within 12 hours of the normal schedule. Despite potential adherence issues, with minimal treatment options for Fabry disease, the hope is that patients will be willing to put in the effort to comply. Amicus expects total global sales of Galafold to reach about $90 million in 2019. Peak annual sales are estimated at $534 million by 2024.
Lilly’s Olumiant (baricitinib) entered the EU rheumatoid arthritis (RA) scene in 2017, followed by a 2019 US launch, giving Pfizer’s first-in-class RA drug, Xeljanz (tofacitinib), its first competition. Both Janus kinase (JAK) inhibitors reduce inflammation in RA patients but carry black box warnings. Future regulatory reviews will continue to examine safety concerns associated with JAK inhibitors, which may be a deciding factor in who wins market share (Xeljanz is also approved for psoriatic arthritis and ulcerative colitis). With improved safety data, a lower price point than Xeljanz, and additional key indications potentially on the horizon, Olumiant could become a blockbuster drug.
Xeljanz was approved by FDA in November 2012 as the first oral JAK inhibitor to treat RA. Four years later, Xeljanz XR, a more convenient once-daily dose, was also approved. Xeljanz didn’t gain EU approval until March 2017, and the extended release formulation has yet to be cleared in Europe.
Conversely, Olumiant’s 2 mg and 4 mg pills were approved in the EU in February 2017. In May 2018, FDA approved only the drug’s 2 mg dose, citing safety issues for excluding the 4 mg dose. This left the US without a possibly more effective Olumiant option.
As a result, almost all US rheumatologists reported using Xeljanz by the end of 2018, while just more than half of EU rheumatologists had done so. Likewise, projections indicate that Olumiant will continue to outpace Xeljanz in Europe.
JAK inhibitors come with inherent safety issues. Because these drugs disrupt the immune system, the body is left susceptible to infection. There are long-term risks for cancer, deep vein thrombosis (DVT), and pulmonary embolism (PE).
However, new data released in June indicated that patients taking the 4 mg dose of Olumiant over seven years showed no significant difference in the rate of DVT or PE. Lilly hopes this information will help achieve FDA approval of the higher dose.
The list price for a 30-day supply of 2 mg Olumiant tablets is $2,136.90. That is 50% less than the cost of Xeljanz. In 2018, Olumiant reported $6.7 million in domestic revenue (it launched at the end of Q2) and $195.9 million outside the US. According to analysts, Olumiant could become a $2.4 billion brand by 2022; key factors will be achieving FDA approval for the 4 mg dose and continuing to highlight its lower price point. Approval for additional indications may also bolster sales; Olumiant is in Phase III trials for atopic dermatitis.
Two new JAK inhibitors could reframe Olumiant’s position in the RA market. In April, late-stage trials of Gilead/Galapagos’ filgotinib demonstrated a better safety profile than Olumiant and Xeljanz, yet showed similar effectiveness. Rinvoq, AbbVie’s pre-emptive answer to Humira’s expiring patents, is another to watch. Although its safety data wasn’t as strong as filgotinib’s, the drug received FDA priority review and was approved in early August. As the market expands, cheaper biosimilars will provide added competition as well.
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