FDA steps up user fee under GDUFA III; Merck’s heart drug succeeds in late-stage study

By PharmaCompass

2022-10-13

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On September 30, the US President Joe Biden had signed into law the Food and Drug Administration Reauthorization Act (FDARA), which includes the reauthorization of the Generic Drug User Fee Amendments (GDUFA) through September 2027. In this week’s Phispers, we bring you the new GDUFA III fee structure. In FY 2023, FDA has increased the fee for ANDAs (abbreviated new drug applications) by nearly 7 percent and for DMFs (drug master files) by around 4 percent.

Merck’s experimental drug for pulmonary arterial hypertension – sotatercept – met the main goal in patients with a progressive blood vessel disorder in a late-stage clinical trial. The pharma had acquired the drug last year through its US$ 11.5 billion buyout of Acceleron Pharma.

In approvals, GSK’s Boostrix vaccine has bagged FDA’s add-on approval for use in pregnant women (who are in their third trimester) to prevent whooping cough (pertussis) in infants younger than two months. FDA has also expanded the use of Alnylam Pharmaceuticals’ Oxlumo (lumasiran) to treat advanced primary hyperoxaluria type 1 (PH1).

In deals, Bayer’s subsidiary Vividion Therapeutics has signed a potential US$ 930 million oncology deal with Tavros Therapeutics to discover and develop four novel oncology targets. And Eli Lilly has signed a potential US$ 496 million biobucks deal with Nimbus Therapeutics to discover new targeted therapies that activate a specific isoform of AMP-activated protein kinase (AMPK) for metabolic diseases.

In regulatory news, the FDA has granted a fast-track status to Eli Lilly’s diabetes drug Mounjaro (tirzepatide) to treat obesity. Gilead’s cancer drug Trodelvy has received an FDA priority review for use in heavily pretreated HR-positive, HER2-negative breast cancer. And Regeneron’s Eylea has bagged priority review for use in treatment of retinopathy in preterm babies.

In trial news, Sanofi and its partner Regeneron said its blockbuster drug Dupixent has achieved a significant histological remission of eosinophilic esophagitis (EoE) in children (between one and 11 years of age) in a late-stage trial. And new data from a two-year study of Roche’s Evrysdi has shown improvement or maintenance of motor function in people with SMA, a progressive neuromuscular disease.

European Directorate for the Quality of Medicines and Healthcare has found one major deficiency at Biocon’s API facility in Bengaluru. The troubled New Jersey plant of Lilly was in news once again for a Form 483 issued by the FDA in July.

And the Adderall drug crisis in the US deepened as seven of the nine companies supplying the attention deficit hyperactivity disorder drug have reported shortages. Novartis’ generics unit Sandoz has become the latest company to report difficulty in supplying the drug.

FDA publishes GDUFA III user fees, increases ANDA, DMF fees

Last week, the US Food and Drug Administration (FDA) published the user fee amounts it will collect from manufacturers of pharmaceuticals, generic drugs, biosimilars and medical devices in FY 2023.

FDA adjusts its user fees every year based on factors such as inflation and the number of applications or establishments expected to pay the various fees. This year’s update is significant because it marks the beginning of the new five-year user fee programs.

In FY 2023, the agency increased the fee for ANDAs (abbreviated new drug applications) by nearly 7 percent and for DMFs (drug master files) by around 4 percent.

Enhancements in GDUFA III aim to reduce the number of assessment cycles for generics, support the development and approval of complex generics, and help manufacturers resolve quality issues more quickly.

FDA User Fee Table FY 2023
Generic Drug User Fee Amendments (GDUFA III) (in US$)	FY 2023	FY 2022	FY 2021	Change	% change
Applications:
Abbreviated new drug application (ANDA)	240,582	225,712	196,868	14,870	7
Drug master file (DMF)	78,293	74,952	69,921	3,341	4
Facilities:
Active pharmaceutical ingredient (API) – Domestic	37,544	42,557	41,671	-5,013	-12
API – Foreign	52,544	57,557	56,671	-5,013	-9
Finished dosage form (FDF) – Domestic	213,134	195,012	184,022	18,122	9
FDF – Foreign	228,134	210,012	199,022	18,122	9
Contract manufacturing organization (CMO) – Domestic	51,152	65,004	61,341	-13,852	-21
CMO – Foreign	66,152	80,004	76,341	-13,852	-17
GDUFA program:
Large size operation generic drug applicant	1,620,556	1,536,856	1,542,993	83,700	5
Medium size operation generic drug applicant	648,222	614,742	617,197	33,480	5
Small business operation generic drug applicant	162,056	153,686	154,299	8,370	5

Merck’s heart drug succeeds in late-stage trial, validates US$ 11.5 bn Acceleron buyout

Merck’s decision to acquire Acceleron Pharma for US$ 11.5 billion last year seems to be paying off. An experimental drug for pulmonary arterial hypertension that the pharma had acquired through the buyout – sotatercept – met the main goal in patients with a progressive blood vessel disorder in a late-stage clinical trial.

When compared to placebo, sotatercept helped patients walk significantly further than those given only standard therapy in a six-minute test after 24 weeks of treatment. The test is a common measure used in trials of cardiovascular disease drugs. The drug also delayed death or worsening of the disease and showed statistical significance on eight of nine secondary endpoints. Merck will present detailed data on the drug at an upcoming medical meeting.

The FDA has granted sotatercept the status of a breakthrough therapy. There are two more trials underway – one in newly diagnosed patients, and another that includes patients who report symptoms even while resting.

To develop, sell personalized mRNA vaccine with Moderna: Merck has decided to jointly develop and sell a personalized mRNA vaccine along with Moderna. Merck’s blockbuster immunotherapy – Keytruda – is being tested in combination with Moderna’s experimental vaccine — mRNA-4157 — in a mid-stage trial to treat patients with melanoma. Data on the vaccine is expected later this year. Merck will make an upfront payment of US$ 250 million to Moderna in exchange for joint development and future commercialization of the vaccine.

FDA grants fast-track status to Lilly’s diabetes drug Mounjaro to treat obesity

The FDA has granted a fast-track status to Eli Lilly’s diabetes drug Mounjaro (tirzepatide) to treat obesity, making the potential blockbuster drug eligible for an expedited review. Following the FDA decision, the Indiana-based drugmaker will submit data on a rolling basis this year, while waiting for the results of the second phase 3 trial (expected in April 2023). In April this year, Lilly had reported positive results from the first late-stage trial of Mounjaro in obesity, stating that people who received an injection of Lilly’s drug lost up to 21 percent of their body weight.

New quality problems at New Jersey plant: Back in November 2019, the FDA had found quality-control issues at Eli Lilly’s manufacturing plant in Branchburg, New Jersey. The agency had classified the findings as Official Action Indicated (OAI). Last year, the US Department of Justice launched an investigation into allegations of poor manufacturing practices and data falsification at the facility. In July this year, the FDA had issued a Form 483 to the same plant post a 12-day inspection owing to several quality-control issues, Reuters reported. The site currently manufactures several major products, including diabetes drug Trulicity, migraine treatment Emgality and cancer drugs. The site also manufactured the antibody bamlanivimab during the Covid-19 pandemic.

Bayer’s Vividion signs potential US$ 930 million oncology deal with Tavros

Bayer subsidiary Vividion Therapeutics and oncology company Tavros Therapeutics have signed a potential US$ 930 million five-year collaboration agreement to discover and develop four novel oncology targets.

Under the terms of the deal, the Californian biotech will hand over US$ 17.5 million to Tavros in cash. The latter will be eligible for US$ 430.5 million in milestone payments. Vividion will also have the option to add up to five additional targets to the collaboration, for which it will have to pay up to US$ 482 million more to Tavros. Tavros is also eligible for royalties.

Lilly inks biobucks deal with Nimbus: Lilly has signed a potential US$ 496 million biobucks deal with Nimbus Therapeutics to discover new targeted therapies that activate a specific isoform of AMP-activated protein kinase (AMPK) for metabolic diseases. Lilly will also be responsible for global development and commercialization. Along with various research, development and commercialization milestone payments totaling up to US$ 496 million, Nimbus will also be eligible for tiered royalties on global net sales of any products.

GSK’s Boostrix vaccine gets add-on approval to prevent whooping cough in infants

The FDA has approved the expanded use of the GSK’s Boostrix vaccine in pregnant women who are in their third trimester to prevent whooping cough (pertussis) in infants younger than two months. When Boostrix is given during pregnancy, it boosts antibodies in the mother, which are transferred to the developing baby, the agency said.

Of the total whooping cough cases in the US in 2021, 4.2 percent were infants younger than six months and 31 percent of those required hospitalization. The vaccine generated £521 million (US$ 576 million) for GSK last year.

Alnylam’s rare disease drug secures add-on approval: FDA has approved the expanded use of Alnylam Pharmaceuticals’ Oxlumo (lumasiran) to treat advanced primary hyperoxaluria type 1 (PH1). The label will also include patients with the most severe kidney impairment, including hemodialysis. The approval is based on positive six-month data from a phase 3 study conducted in PH1 patients with severe renal impairment, including those on hemodialysis. PH1 is a rare disorder that mainly affects the kidneys. It results from buildup of a substance called oxalate.

Sanofi, Regeneron flaunt Dupixent’s benefit in eosinophilic esophagitis trial in kids

Sanofi and its partner Regeneron said their blockbuster drug Dupixent achieved a significant histological remission of eosinophilic esophagitis (EoE) in children between the ages of one and 11 years in a late-stage trial. EoE is a chronic inflammatory disease that damages the esophagus and prevents it from working properly.

In the phase 3 trial, 68 percent children on a higher dose and 58 percent on a lower dose of the drug achieved significant histological disease remission as compared to just 3 percent in the placebo group. The drugmakers plan to submit the data to the FDA in 2023. If approved, Dupixent would be the first treatment for EoE patients under the age of 12 years.

Two-year data on Roche’s Evrysdi shows benefit in spinal muscular atrophy

Roche has announced new data from a two-year study evaluating Evrysdi (risdiplam) in people with type 1, 2 or 3 spinal muscular atrophy (SMA) aged between six months to 60 years at the time of enrollment. These patients had been previously treated with other approved or investigational SMA-targeting therapies, including nusinersen (Spinraza) or onasemnogene abeparvovec (Zolgensma).

The data showed Evrysdi improved or maintained motor function and led to rapid increases in SMN protein levels, which were sustained after two-years of treatment. Known as Jewelfish, the study enrolled the broadest and most diverse patient population ever studied in an SMA trial.

Gilead’s Trodelvy wins priority review: Gilead said its cancer drug Trodelvy has received an FDA priority review for use in heavily pretreated HR-positive, HER2-negative breast cancer. FDA is slated to take a decision by February next year, it added.

The California-based drugmaker said the antibody-drug conjugate reduced the risk of disease progression or death by 34 percent. The drug also cut the risk of death compared to a physician-picked chemotherapy by 21 percent, helping extend patients’ lives by a median of 3.2 months.

Regeneron’s Eylea bags priority review for retinopathy in preterm babies: The FDA has accepted Regeneron Pharmaceuticals’ supplemental biologics license application (sBLA) for Eylea (aflibercept) injection to treat ‘retinopathy of prematurity (ROP)’ in preterm infants. The target action date for the FDA decision is February 11, 2023. ROP is a leading cause of childhood blindness worldwide. The rare eye disease often impacts infants who are born before 31 weeks of pregnancy or who weigh less than 1.5 kg at birth.

US ADHD drug crisis deepens as Novartis’ Sandoz also reports shortage of Adderall

Amid a US-wide shortage of Adderall and its generics, the list of companies that are having difficulty supplying the attention deficit hyperactivity disorder (ADHD) drug is growing. At present, seven of the nine companies supplying the prescription drug have reported shortages.

Novartis’ generics unit Sandoz — the second-largest supplier of Adderall in the US — said it is having difficulty in supplying the immediate-release version of the drug. Earlier, the company had reported a shortage of the extended-release version of Adderall.

In August, Teva Pharmaceuticals, the largest seller of Adderall in the US, had reported difficulty supplying 20-mg and 30-mg Adderall tablets. It had blamed the issue on “packing capacity constraints” and labor shortage. Since then, several other companies, including Amneal, Purdue Pharma’s subsidiary Rhodes Pharmaceuticals , Par Pharmaceuticals, Camber Pharmaceuticals and Sun Pharma, have reported supply problems. Around 2.5 million Americans rely on medications such as Adderall to manage their ADHD.

EDQM finds one major deficiency at Biocon’s API facility in Bengaluru

Back in August, the FDA had issued Form 483s with 11 observations each to two Biocon Biologics facilities in Bengaluru, India. Another Biocon Biologics plant in Johor, Malaysia, had also received a Form 483 with six observations.

Now the European Directorate for the Quality of Medicines and Healthcare (EDQM) has found one major deficiency at its Bengaluru active pharmaceutical ingredient (API) plant, Biocon said. The agency had conducted an inspection of the site from September 12-14.

Biocon said there were no critical deficiencies, and the agency has cited one deficiency under the category ‘major’. The company said it will respond to the agency with appropriate corrective and preventive actions within the stipulated time.

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