Next week’s J.P. Morgan Healthcare Conference in San Francisco is the traditional kick-off of the year for biopharma. At an impossibly packed St. Francis Hotel, companies’ executive teams outline their agendas for the year, followed by grilling from investors and analysts during breakout sessions.
Naturally, most of the big events that will occur in the first year of the third decade of the 21st century are unforeseeable. But there are some – like anticipated regulatory decisions by the Food and Drug Administration, ongoing trends in the industry and politically sensitive issues ahead of the presidential election – that are easier to forecast.
Executives of biopharma companies and an academic expert specializing in areas like rare diseases, cancers and cardiovascular disease weighed in on what to expect as the year unfolds.
With numerous companies submitting New Drug Applications and Biologics License Applications to the FDA last year, a number of decisions by the agency are anticipated this year, particularly in hot areas like cell and gene therapies. According to Dr. John Zaia, director of the Center for Gene Therapy at City of Hope in Duarte, California, much of the focus of gene therapy will likely be in areas like hematology, immunology and metabolic diseases.
“All those three areas are where gene therapy will have its place,” Zaia said in a phone interview. “We’ve been saying that for the last 15-20 years, but now, methodologies have been so good that we’re ‘harvesting’ the years of labor.”
The two currently approved gene therapies – Roche’s Luxturna (voretigene neparvovec-rzyl) and Novartis’ Zolgensma (onasemnogene abeparvovec-xioi) – are respectively approved for an inherited form of blindness and spinal muscular atrophy. But several in the areas Zaia highlighted are coming down the pike, either up for regulatory decisions in the near future or in registrational development. These include bluebird bio’s Zynteglo for the blood disorder beta-thalassemia – already approved in Europe – and product candidates from other companies for diseases like hemophilia; and Orchard Therapeutics’ OTL-200 for the metabolic disorder metachromatic leukodystrophy.
CAR-T cell therapies likely to see FDA decisions this year include Bristol-Myers Squibb’s lisocabtagene maraleucel, for non-Hodgkin’s lymphoma, as well as bluebird and BMS’ idecabtagene vicleucel for multiple myeloma.
Another class of therapies aimed at rare diseases that has seen significant growth is RNA-interference, or RNAi drugs. The FDA approved the first RNAi drug, Alnylam Pharmaceuticals’ Onpattro (patisiran) for hATTR amyloidosis, in August 2018. And in November 2019, Alnylam also won approval for the second-ever RNAi drug, Givlaari (givosiran), for acute hepatic porphyria. And Barry Greene, the Cambridge, Massachusetts-based company’s president, sees more of them coming, with the company hoping to double the number of RNAi drugs on the market by the end of this year.
“The excitement and interest in RNAi is palpable: Today, the combined market cap for major RNA companies is more than $55 billion, and there are five RNA-targeting medicines on the market,” Greene wrote in an email.
Further illustrating the popularity of RNAi was Novartis’ $9.7 billion acquisition in November of The Medicines Co., which is partnered with Alnylam in the development of inclisiran, designed to prevent production of the protein PCSK9 in the liver in order to treat inherited hypercholesterolemia.
Another rapidly growing area in oncology is highly targeted small-molecule drugs, whose development is driven by the increasing use of next-generation sequencing and the growing view of cancers as genomic rather than tissue-based diseases.
Illustrating the growth of such targeted therapies, one of the first major acquisition deals of 2019 was Indianapolis-based Eli Lilly’s $8 billion purchase of Loxo Oncology, which originally developed Vitrakvi (larotrectinib), designed to treat tumors that express a genetic anomaly known as an NTRK fusion. Following the Lilly deal, Loxo handed rights to Vitrakvi to its former partner, Bayer, but has been developing other highly targeted drugs since then.
Another company in this area is Cambridge, Massachusetts-based Blueprint Medicines, which has a drug called avapritinib, for exon 18-mutant gastrointestinal stromal tumors.
“In the coming year, I predict more precision therapies will be introduced at the intersection of oncology and rare diseases,” wrote Philina Lee, Blueprint’s vice president for marketing, patient services and U.S. precision medicine, in an email.
Lee pointed to avapritinib, as well as Epizyme’s EZH2 inhibitor tazemetostat, for epithelioid sarcoma, as both being under FDA review and having potential to be important advancements in treatment of sarcomas, which are connective-tissue cancers. Ensuring these drugs get to their intended patient populations will continue to be a challenge, given the lack of genomic sequencing infrastructure in community cancer practices and hospitals with less standardized testing practices. But precision medicine initiatives in community oncology networks to educate and develop guidelines for biomarker testing are already taking place, she wrote.
While cell and gene therapies, RNAi drugs and targeted therapies have already saved or improved the lives of many patients, what tends to get much of the attention – particularly from the lay press and politicians – is their high list prices, which can run into the hundreds of thousands or millions of dollars.
Granted, list prices are distinct from the out-of-pocket costs that patients actually have to pay themselves, but they can still exert enormous costs on the healthcare system while playing a role in high out-of-pocket costs as well. Despite eye-popping list prices’ political sensitivity, especially in an election year, Tom Mayleben, CEO of Ann Arbor, Michigan-based cardiovascular drugmaker Esperion Therapeutics, does not see politics as the likely solution to the problem.
“Drug pricing is going to continue to be the most talked-about aspect of our industry, but I tend to think that rather than legislation fixing all of this, we as an industry come to our senses, and we actually do some things,” Mayleben said in a phone interview. That would mean the industry taking steps to self-regulate when it comes to pricing.
But politics may hold the solution to the even more sensitive issue of out-of-pocket costs, with the drug industry remaining unable to address it on its own.
“That’s not just a pharmaceutical industry issue – it’s an insurance industry issue and a provider issue,” Mayleben said, adding that costs to patients have gotten “out of control” in the last 7-8 years. “That’s one where we could see legislation.-Med City News