[Updated, 3:40 pm ET, see below] The Food and Drug Administration approved 59 new drugs last year, a record for the agency which over the years has swung back and forth between tight control and leniency. We are in the midst of perhaps the agency’s most permissive era ever, thanks to its openness to speed up reviews and to greenlight certain drugs with slim evidence, like those for cancer patients who have run through all other options, or for kids with rare diseases and no available treatments.
The pace appears slower this year, but the agency just green-lighted a new drug for treatment-resistant tuberculosis, and it could approve as many as four more new drugs by early next week, all of them notable for different reasons. One taps into a history of FDA drama. Another is a bellwether for companies hoping to fight off “superbug” infections. A third makes the case for precision cancer treatment, and a fourth is a key part of pharma’s ongoing fight against generic competition. Here’s a thumbnail preview of each.
Duchenne… without the drama?
The FDA made one of its most controversial decisions ever when it granted “accelerated” approval to the Duchenne muscular dystrophy drug eteplirsen (Exondys 51) in 2016 on the slimmest of evidence. Now a follow-on drug, also from Sarepta Therapeutics (NASDAQ: SRPT), is on the agency’s desk. Despite some similarities, there isn’t much controversy expected.
Like Exondys 51, the new medicine golodirsen (Vyondys 53) is an RNA-based drug meant to produce a truncated form of the shock-absorbing protein, dystrophin, that Duchenne patients lack. Exondys is for 13 percent of Duchenne patients with a particular genetic profile; Vyondys 53 is for a different 8 percent of Duchenne patients. Both are weekly infusions given chronically.
Another similarity: The main evidence for both drugs was their ability to help patients produce around 1 percent of normal levels of dystrophin, known as a “surrogate” marker because the studies—which were tiny—did not conclusively show that patients were benefiting from treatment.
With Exondys 51, that evidence still doesn’t exist. The clock is ticking. Under the 2016 approval agreement, Sarepta must show the FDA that Exondys 51 is providing meaningful health benefits to patients by 2021. As STAT reported Thursday, Sarepta is running behind: results are expected in 2024.
When Exondys 51 was under review in 2016, some patient advocates argued at a dramatic advisory meeting that the drug was making a difference, but Sarepta’s studies weren’t showing it. Top drug evaluator Janet Woodcock ultimately supported the drug, and Exondys was approved. (As Xconomy reported here, two advocates started a company, Casimir Trials, to try to better measure the effects of Duchenne drugs and other rare disease medicines in the wake of the Exondys saga.)
Sarepta has a similar surrogate-marker story for Vyondys. Again, there isn’t evidence yet that the drug is improving outcomes. The nonprofit drug pricing watchdog ICER called the results “insufficient” in a recent report on Vyondys and other Duchenne medicines.
Yet there is one important difference with Vyondys: It seems to produce more dystrophin than Exondys. There was no advisory meeting scheduled this time, often a positive sign for a drug’s prospects. Wall Street analysts are bullish on Vyondys’s odds. SVB Leerink analyst Joseph Schwartz, for instance, gave the drug a 90 percent chance of approval.
AbbVie (NYSE: ABBV) agreed to buy Allergan (NYSE: AGN) for $63 billion partly to prepare for generic competition to adalimumab (Humira), the world’s top-selling drug. But one of its ace cards comes from up its own sleeve: the anti-inflammatory drug upadacitinib, which AbbVie has been developing as Humira’s successor and has bested Humira head-to-head.
Upadacitinib’s first indication is rheumatoid arthritis. Even with FDA approval, it will face new competition. A new class of oral medications called JAK inhibitors have wrested some market share away from Humira and other so-called TNF inhibitors, which must be injected. Pfizer brought the first JAK inhibitor for RA, Xeljanz, to market in 2012, and it notched $1.8 billion in sales in 2018. Others are either on the market (Olumiant, from Eli Lilly, approved in June 2018), or in development (filgotinib, from Gilead Sciences).
Upadacitinib is the next JAK inhibitor in line. In addition to RA, the drug is being tested in four other mid- or late-stage trials. EvaluatePharma projects that the drug could generate $2.5 billion in yearly sales for AbbVie by 2024, with a majority coming in RA. AbbVie executives have said that upadacitinib and another recently approved drug, risankizumab (Skyrizi), could fill a Humira-sized hole by 2025, bringing in combined more than $10 billion annually. (Drug-sales projections, however, have a history of going off the rails.)
But there are concerns. The FDA slapped a safety warning on Xeljanz last month, meaning two drugs in the class are now tied to potential health problems. That decision highlighted “potential safety risks for the JAK inhibitor class overall,” wrote RBC Capital Markets analyst Brian Abrahams, And that’s why all eyes are on the FDA’s upcoming decision on AbbVie’s drug.
“Our program hasn’t demonstrated that risk,” AbbVie vice chairman and president Michael Severino said on a conference call last week. If the FDA issued a warning about upadacitinib, it would be evidence of “some form of class labeling,” he said.
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