5 FDA approval decisions to watch in Q4

 The Food and Drug Administration has already made several weighty regulatory decisions this year, but crucial drug reviews still lie ahead.

Top among them are decisions on whether to clear COVID-19 shots for children and boosters for others, each of which represent challenging and controversial calls for an agency that will soon lose two of its top vaccine reviewers. And Merck & Co. just gave the FDA another must-do item, as it's likely to soon file an application for what could be the first pill for COVID-19.

But the agency, as always, has much more on its plate. A new cell therapy for multiple myeloma, for instance, could be the latest treatment for a disease that's seen an array of drugs emerge over the past decade. The first medicine for dwarfism could be on its way, as well as a potentially valuable treatment option for a form of depression. Read on for details on each:

Pfizer and BioNTech's coronavirus vaccine for children

The spread of the infectious delta variant has added urgency to COVID-19 vaccination campaigns. But children under 12 years old still aren't eligible, making kids the country's most vulnerable group just as the new school year gets underway and the delta-driven wave peaks. That's been reflected by a steady rise in cases: Kids have accounted for at least 200,000 infections each of the past five weeks and more than a quarter of the nation's total the week of Sept. 23, according to the American Academy of Pediatrics.

That trajectory could begin to change if the FDA authorizes Pfizer and BioNTech's vaccine for school-age children between 5 and 11 years old. The companies submitted study results to U.S. regulators in September after their vaccine sparked a similar immune response in children to what was seen in 16- to 25-year-olds. They expect to file for emergency authorization within weeks.

A green light from the FDA could reportedly come in November, but the agency's decision won't be easy. Children are far less susceptible to severe COVID-19 than adults. And while Pfizer has said its shot was safe in clinical testing, the drugmaker hasn't yet detailed the prevalence of a rare type of heart inflammation seen in some vaccinated younger men — a key concern of the FDA and its advisory panel.

Johnson & Johnson's cilta cel for multiple myeloma

Earlier this year, Bristol Myers Squibb and partner Bluebird Bio's Abecma became the first cancer cell therapy cleared to treat multiple myeloma. But right on their heels are another duo, Johnson & Johnson and Legend Biotech, who could soon bring a similar, rival treatment, known as cilta cel, to market as well.

Like Abecma, cilta cel is part of an emerging class of treatments targeting the protein BCMA, which is overexpressed on cancerous cells. While both drugs have proven to be very potent at driving the blood cancer into remission for people who have progressed despite multiple treatments, J&J and Legend's treatment could have an edge.

In the study supporting Abecma's approval, for instance, 72% of patients responded to treatment and a third of them went into remission. Though it's difficult to compare drugs across trials, 98% of patients in J&J and Legend's key study responded, and 80% were in remission a year and a half after treatment.

The FDA is expected to make a decision by Nov. 29, which could kick off a commercial battle between the two groups. But more competition could follow, as Regeneron, AbbVie and several others, including J&J itself, have BCMA-targeting antibody drugs in advanced testing.

Moderna's and J&J's coronavirus vaccine boosters

Coronavirus booster shots are officially rolling out in the U.S., even though there remains much debate about who needs them and the impact they'll have.

But the FDA, so far, has only cleared third shots for a subset of people who have received Pfizer and BioNTech's coronavirus vaccine. That leaves the roughly 82 million Americans who've received one of the two other shorts authorized in the U.S., from Moderna and Johnson & Johnson, wondering if or when they'll be able to receive a boost as well.

The answers could come soon. The FDA is currently reviewing data in support of a third dose for Moderna vaccine recipients. That dose would be half the size of the one used in the two-shot regimen regulators have already cleared and, as Pfizer has argued, is meant to restore any protection that may have waned with time.

J&J, meanwhile, may not be far behind. The company recently revealed trial data showing an increase in protection for those who received a second shot eight weeks after their first. The pharma company has yet to submit an application for the additional dose, though it has shared the study details with the FDA.

Intra-Cellular's lumateperone for bipolar depression

About 3% of adolescents and 4.4% of adults in the U.S. will develop bipolar disorder in their lives, according to estimates from the National Institute of Mental Health.

The condition causes extreme changes in mood and energy levels, with patients alternatively experiencing episodes of euphoric highs and severe depression. Though medications are available, doctors and researchers agree there remains a significant need for additional drugs.

Intra-Cellular Therapies is looking to provide a new option with lumateperone, a drug the FDA cleared in 2019 to treat schizophrenia and is sold under the brand name Caplyta. In May, the company asked the FDA to approve lumateperone again, this time for depressive episodes associated with bipolar I or II disorder. A decision from the agency should come by Dec. 17.

Intra-Cellular has completed three late-stage clinical trials in bipolar disorder. Two of them succeeded, while the third failed because of a higher-than-expected placebo response, the company claimed.

The most recent of these trials to wrap up, called Study 402, evaluated lumateperone by itself and as an adjunctive therapy to the depression medications lithium and valproate. It found patients who were on a high dose of lumateperone scored about two and a half points better on a scale for measuring depression, compared to patients who just got placebo.

Jefferies analyst Andrew Tsai believes there is a 75% chance the FDA greenlights an expanded label, which would open the door to a much larger marketing opportunity. Tsai projects $1.5 billion to $2 billion in peak sales for Intra-Cellular's drug across schizophrenia and bipolar disorder.

BioMarin's vosoritide for achondroplasia

BioMarin Pharmaceutical sells six drugs for rare diseases. Its seventh, a rare feat of repeat success in biotech, is approved in Europe and could be cleared in the U.S. by late November, when the FDA is expected to reach a decision.

This seventh drug is a bit different than the six that came before it, all of which treat diseases caused by breakdowns in cellular metabolism. Vosoritide, as it's known scientifically, is for achondroplasia, the most common cause of dwarfism. It would be the first drug available for the condition in the states if approved, as it was in Europe when regulators cleared it there in August.

The FDA was set to decide on approval by August, too, but extended its review to go over two-year results that BioMarin submitted from a Phase 3 trial. Those results have shown that treatment with vosoritide led to greater gains in height than a placebo in year two, and position BioMarin well for a positive decision.

But the company has been surprised before, most notably with its Roctavian gene therapy for hemophilia that was unexpectedly rejected by the FDA in August 2020. The regulator is scheduled to issue its verdict by Nov. 20.

If approved, vosoritide would likely be costly. In France, where BioMarin set up an early access plan with regulators, the company is charging roughly $300,000 per patient per year.

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