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Innovation on hold during the pandemic? FDA says no with 29 approvals in first half of 2021

Many pursuits have been put on hold during the coronavirus pandemic. But biopharmaceutical innovation isn’t one of them. In 2020, the FDA approved 53 new drugs, the second-most in a single year, after 2018’s bounty of 59.

And the momentum has continued through the first half of 2021. With the FDA endorsing its 29th novel drug on June 30, the industry was slightly ahead of last year’s pace.

No. 29 came last week with a green light to Jazz Pharmaceuticals for its blood cancer therapy Rylaze. It was the first FDA approval in 23 days.

Perhaps the U.S. regulator needed a break after the uproar that ensued after its June 7 nod for Biogen’s Alzheimer’s disease treatment Aduhelm. It was an approval so divisive that three members of the FDA’s advisory committee that reviewed the drug quit in protest. In his resignation letter to acting FDA commissioner Janet Woodcock, Harvard Medical School professor Aaron Kesselheim called the move a “debacle” and “probably the worst drug approval decision in recent U.S. history.”

Within hours of its green light, Biogen ignited another firestorm when it revealed the treatment’s annual price tag of $56,000 and provided a new flashpoint for the decades-old drug-pricing debate.

Before the Aduhelm controversy eclipsed everything else, the year had featured a lot of other high-profile approvals. GlaxoSmithKline and ViiV Healthcare earned a nod for Cabenuva, a long-awaited monthly injectable for those with HIV. ADC Therapeutics won a green light for Zynlonta, the first single-agent CD19-targeted antibody-drug conjugate for diffuse large B-cell lymphoma. And Apellis scored with Empaveli for the rare, chronic blood disorder paroxysmal nocturnal hemoglobinuria (PNH).

Another high-profile approval came in late May for Amgen’s new cancer drug Lumakras. The non-small cell lung cancer treatment has been highly anticipated, as it targets KRAS mutations which were previously believed to be “undruggable.”

The green light for Lumakras triggered a Memorial Day weekend splurge for the FDA. On the same Friday afternoon, Alkermes’ schizophrenia drug Lybalvi and BridgeBio’s bile duct cancer therapy Truseltiq also won approvals. Then the Tuesday after the holiday, Scynexis gained an FDA nod for its potential blockbuster Brexafemme, the first new treatment for vaginal yeast infection in more than two decades.

The approval for Truseltiq was particularly noteworthy because it was the second this year for tiny BridgeBio, which reported $8.2 million in revenue last year.

The only other firms with two approvals in the first half are companies on the other end of the industry spectrum. Pharma giant Johnson & Johnson earned nods for NSCLC antibody Rybrevant and multiple sclerosis therapy Ponvory. Bristol Myers Squibb scored two CAR-T approvals, as well.

In terms of treatment areas, it is of little surprise that oncology accounts for 12 of this year’s approvals. That figure represents 44% of all new drug approvals this year, an even higher rate than in 2020 when 20 of 53 new drugs were in the oncology class.

Even during a pandemic, don’t expect the pace of innovation to subside. It’s a sign of the times, and successes will only fuel further innovation, according to Ernst & Young industry analyst, Arda Ural.

“The acceleration in the successful development of truly novel platform technologies and therapeutics offers the opportunity for higher returns on investment and are driving pipeline priorities,” Ural wrote in his analysis of first-quarter trends this year. “Gene therapy, mRNA vaccines and therapeutics, cell therapy and gene editing once seemed like science fiction but now are a reality.”

Below, find summaries of several high-profile approvals that have come so far in 2021. The FDA’s roundups of 2021’s novel drug approvals can be found here and here.

Abecma (Bristol Myers Squibb)

Just about a month after Bristol Myers Squibb’s high-profile CAR-T approval for lymphoma med Breyanzi, the company ushered another highly anticipated cell therapy across the FDA finish line.

In late March, BMS scored FDA approval for Abecma, the first CAR-T drug to treat multiple myeloma. The FDA based its decision on data from a phase 2 trial called KarMMa, which showed the drug triggered a response in nearly three-quarters of patients with heavily pretreated and highly refractory multiple myeloma.

While Abecma has the first-mover advantage in the multiple myeloma CAR-T arena, its days as the lone option in the field are limited. Johnson & Johnson and Legend Biotech’s cilta-cel has scored an FDA priority review, and some analysts believe it has a favorable clinical profile compared to the BMS offering.

Like Breyanzi, BMS’ other cell therapy, Abecma is the focus of a manufacturing expansion effort at the drugmaker. After the pair of cell therapy approvals during the first half of 2021, BMS has outlined manufacturing expansions in Massachusetts and the Netherlands to bolster its cell therapy production.

Aduhelm (Biogen)

In one of the most controversial FDA approvals in years, Biogen managed to pluck its Alzheimer’s drug Aduhelm out of the reject pile and usher it across the agency’s finish line despite a resounding rejection from the FDA’s own advisors. With that nod, Aduhelm, also known as aducanumab, became the first Alzheimer’s drug approved in nearly two decades and the first intended to treat the course of the disease, rather than just its symptoms.

But after weeks of fiery backlash, Biogen and the FDA have been left to answer to a heap of concerns over the treatment.

Chiefly among them has been the drugmaker’s decision to set Aduhelm’s list price at $56,000 per year despite its murky clinical benefits. At that price, some estimate Medicare’s bill for just the Biogen treatment could swell above total spending for all Part B drugs combined. That’s partly thanks to the FDA’s highly disputed decision to grant access to all Alzheimer’s patients instead of restricting use to those with early onset disease.

Notably, the agency used the removal of amyloid plaque as a surrogate endpoint, rather than approving based on hard data showing a clinical benefit in terms of slowing cognitive decline. The agency allotted the company a window of nine years to conduct a follow-up trial to determine whether the drug actually does benefit patients’ daily lives.

Meanwhile, Capitol Hill’s unease has gone from a simmer to a boil, pushing two high-ranking Democratic lawmakers to launch an investigation to address “serious concerns about the steep price” of Aduhelm, as well as the “process that led to its approval despite questions about the drug’s clinical benefit.”

Brexafemme (Synexis)

Little-known before the approval of its antifungal to treat vaginal yeast infection, Jersey City’s Scynexis now finds itself the “loudest and only voice” in the generic-dominated field, CEO Marco Taglietti said on a recent call with investors. On June 1, Brexafemme won the FDA’s blessing as the first new antifungal class approved for the condition in more than two decades.

Vaginal yeast infection, also known as vulvovaginal candidiasis (VVC), affects around 70% to 75% of women at least once in their lifetimes. Despite the condition’s prevalence, innovation has been stagnant since the late 1990s, Cantor Fitzgerald analysts wrote to clients in June.

At a wholesale cost of $475, Scynexis is eyeing peak sales of $400 million to $600 million for its first commercial drug, though there could be “upside scenarios,” said the company’s chief financial officer Eric Francois during a recent launch presentation. Some analysts agree: Brexafemme’s easy dosing, plus its ability to kill the fungal cells behind infection—where azole drugs like Pfizer’s Diflucan fall short—and an “increasing interest by large pharma in the antifungal space,” could see the med hit blockbuster territory with more than $1 billion in annual sales, the Cantor Fitzgerald team said.

Counting down to launch, Scynexis has built out a 70-person sales team with its commercial partner Amplity Health. Meanwhile, the company is already reporting interest in its drug: In a recent Scynexis survey of more than 1,000 healthcare practitioners, 84% of doctors said they’d prescribe Brexafemme to a patient on request, Christine Coyne, the company’s chief commercial officer, said on the investor call.

Breyanzi (Bristol Myers Squibb)

Until Biogen’s June approval for Alzheimer’s drug Aduhelm, Bristol Myers Squibb’s FDA nod for cell therapy Breyanzi may have been the industry’s highest-profile approval of 2021’s first half.

Breyanzi, which won FDA approval in February to treat certain patients with large B-cell lymphoma, has been the focus of numerous big headlines in the industry, including Bristol’s missed multibillion-dollar contingent value right tied to its Celgene buyout back in 2019.

Since the Breyanzi approval, BMS has made commitments to bolster its cell therapy manufacturing on both sides of the Atlantic.

In the market, Breyanzi is squaring off against entrenched cell therapies from Novartis and Gilead. But in a major win in early June, Breyanzi posted positive results in second-line large B-cell lymphoma. The results potentially set up the drug to move up the line in treatment regimens, offering an advantage over those rivals.

Breyanzi, a one-time treatment for a difficult-to-treat cancer, is currently approved for patients who’ve failed at least two other systemic therapies. It carries a list price of $410,300 per patient.

Cabenuva (GlaxoSmithKline)

Cabenuva started a new chapter for HIV treatment. Rather than daily oral pills, the two-drug injectable offers the first complete long-acting HIV regimen that’s given once a month. A combination of GSK’s cabotegravir and Johnson & Johnson’s rilpivirine, the intramuscular therapy showed it could match up to traditional three-drug regimens at suppressing HIV in two phase 3 trials. The drug faced a previous setback at the FDA thanks to manufacturing-related issues, making Canada the first country to approve it last March.

Meanwhile, GSK’s ViiV Healthcare is awaiting an FDA decision to reduce Cabenuva’s dosing frequency to once every two months.

Through a new collaboration with Halozyme, ViiV is also looking to develop “ultra-long-acting” under-the-skin HIV medicines with dosing intervals of three months or longer. While the pair is starting with single-agent cabotegravir for HIV prevention, or PrEP, Cabenuva is also on its list for this update, ViiV’s head of R&D Kimberly Smith, M.D., said in a recent interview.

Cabotegravir-based HIV therapies and the transition to long-acting medicines are GSK’s answer to competition from Gilead Sciences, currently the leader in HIV market. Those drugs are also expected to carry GSK’s HIV business once its current bread-and-butter dolutegravir, sold under the brand name Tivicay and used in other fixed-dose combos, loses its patent protection in 2027.

Empaveli (Apellis Pharmaceuticals)

May was a good month for Apellis Pharmaceuticals’ Empaveli. First, the FDA widely approved the C3 inhibitor to treat patients with the rare blood disorder paroxysmal nocturnal hemoglobinuria (PNH), even for those who had not previously received any treatment. Prior to the agency’s decision, it was unclear whether Empaveli would be relegated to those who didn’t take to its C5 rivals, namely Alexion’s Soliris and Ultomiris.

To be sure, Apellis had a back-up study in the works and, later that month, it revealed that Empaveli “demonstrated statistical superiority” in hemoglobin stabilization and lactate dehydrogenase (LDH) reduction compared with standard of care. With that extra data and an approval in hand, Apellis has been able to target the 1,500 PNH patients already on a C5 inhibitor as well as the roughly 150 people who are newly diagnosed every year, David Acheson, Apellis’ North America commercial vice president, said in late June.

Of those who have been switched over from a C5 inhibitor during Empaveli’s rollout, Acheson said about 60% have come from Ultomiris. But Apellis isn’t stopping there: The company is gunning for a new indication in geographic atrophy, an age-related condition marked by the degeneration of the macula in the eye, that could bring in about $1 billion in annual sales. Apellis is expecting key phase 3 data later this quarter.

Lumakras (Amgen)

In the quest to crack the code on the KRAS protein, Amgen made history this year with its oncology blockbuster-in-waiting, Lumakras. Approved three months ahead of schedule for non-small cell lung cancer (NSCLC) patients with a genetic mutation dubbed KRAS G12C, Lumakras is now the first therapy to strike a blow against a tumor target once deemed undruggable.

With KRAS G12C accounting for some 13% of NSCLC mutations, pinpointing patients who can benefit from Lumakras will be key to the drug’s success. To that end, Amgen has teamed with diagnostics majors Guardant Health and Qiagen, both of whom scored companion diagnostic green lights alongside Lumakras.

Some analysts, like Mizuho’s Salim Syed, have flagged NSCLC patients’ mutation status as a potential hurdle on arrival for Lumakras.

For its part, Amgen is working with providers to get that info on the front pages of their pathology reports, EVP of commercial operations Murdo Gordon said on a recent investor call. The company also expects Lumakras’ nod to accelerate testing “fairly rapidly.”

With a $17,900-a-month price tag, the drug has the potential to surpass $100 million in first-year sales, Jefferies analysts wrote to clients in May. Meanwhile, analysts at Cantor Fitzgerald forecasted $2.5 billion in peak sales for the drug. While it’s snared the gold, Amgen isn’t flying solo in the KRAS race. Notably, Mirati therapeutics is angling for second place with its product adagrasib, which scored a breakthrough therapy tag from the FDA in late June.

Zynlonta (ADC Therapeutics)

While several new CAR-T medicines against diffuse large B-cell lymphoma have debuted in recent years, ADC Therapeutics’ Zynlonta takes a different approach to attack the disease. With an FDA approval in April, the newly commercial biotech is launching the first single-agent CD19-targeted antibody drug in the field.

Like other new DLBCL drugs, Zynlonta is approved for patients who have failed on two prior systemic therapies. But unlike its rivals, which are intended to be one-time treatments, Zynlonta requires dosing every three weeks.

In May, the drug scored inclusion in the National Comprehensive Cancer Network treatment guidelines for large B-cell lymphomas. In a phase 2 trial, Zynlonta turned in an overall response rate of 48.3%, and for those who responded, the median duration of response was 10.3 months. More than 24% of patients experienced a complete response in the trial. After the approval, ADC tapped its clinical manufacturing partner, Avid Bioservices, to help produce commercial supplies. One vial of the drug costs $23,500 before rebates or discounts, according to reports.