On April 5th, the legendary CAR-T therapy Carvykti of Legend Biotech reached a key PDUFA milestone
The next landmark event for Chinese innovative drugs going global is about to happen.
On April 5, 2023, Legend Biotech's BCMA CAR-T therapy Carvykti (siltuximab) will reach a key milestone with the PDUFA (Prescription Drug User Fee Act, which, once passed, means approval for market launch), becoming the first true representative of Chinese innovative drugs going global.
In March before this, this highly anticipated new drug had already received unanimous expert approval at the FDA Oncologic Drugs Advisory Committee (ODAC) meeting with a vote of 11:0.
This decision was mainly based on the results of the CARTITUDE-4 (NCT04181827) study, the first randomized Phase 3 study evaluating the efficacy and safety of CARVYKTI in the treatment of relapsed and refractory multiple myeloma (MM) patients who have received one to three prior lines of therapy and are resistant to lenalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, bortezomib, and dexamethasone (DPd).
It is widely expected in the industry that Carvykti will be formally approved by the FDA on April 5, bringing new treatment options for MM patients.
Frontline approval brings expectations for the next round of growth
Carvykti was approved for marketing in the United States in February 2022 for the fifth-line treatment of relapsed/refractory MM. Legend Biotech revealed in a previous conference call that the market share for this indication in the U.S. is approximately 80%. Despite the indication being relatively late-stage, with its outstanding efficacy and safety, Carvykti generated sales revenue of $469 million in the U.S. in 2023, accounting for 94% of its total revenue.
Two pivotal studies for MM treatment beyond the fourth line (CARTITUDE-1 and KarMMa) showed that Carvykti achieved an overall response rate (ORR) of 97%, higher than the 73% of Abecma from Bristol Myers Squibb (BMS), making it the best-in-class CAR-T product in this indication.
Moreover, with better efficacy, Carvykti is priced at $465,000, higher than Abecma's $419,500.
As Carvykti advances towards early-stage MM treatment, it is expected to benefit more patients, which means significant sales revenue for Legend Biotech and Johnson & Johnson.
Previously, Carvykti had received unanimous approvals for expanded indications from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency and the FDA Oncologic Drugs Advisory Committee (ODAC), with the potential to be approved in the first half of this year.
It is widely believed in the industry that expanding into frontline treatment is an important way to achieve revenue growth for CAR-T therapy. Johnson & Johnson previously estimated in a conference call that by 2027, Carvykti's annual sales could reach $4.5 billion
Further Cooperation with Novartis to Solve Production Capacity Bottleneck
Against the backdrop of the imminent approval of second-line treatment indications, Legend Biotech and Johnson & Johnson are accelerating the commercial layout of Carvykti to address the issue of insufficient production capacity.
In order to meet the growing market demand, in March 2024, Legend Biotech and Johnson & Johnson reached a new production cooperation agreement with Novartis.
According to this agreement, Novartis will provide commercial production support for Carvykti at its factory in Morris Plains, New Jersey, until the end of 2029. Legend Biotech and Johnson & Johnson have committed to meeting specific production targets and implementing tiered pricing based on the ordered batch quantities.
Previously, Legend Biotech revealed during a conference call that the company is undergoing a $1 billion capital expenditure plan to reach a production level of 10,000 doses by the end of 2025.
It is worth mentioning that Legend Biotech and Johnson & Johnson had previously encountered bottlenecks in production. However, with the new factory in Ghent, Belgium, starting clinical production four months ago, and the increase in production capacity at the commercial production base in Raritan, New Jersey, the production capacity issue is expected to be alleviated.
Expectation for CAR-T Safety Issues to Improve After this PDUFA
However, as an innovative therapy, the long-term safety of CAR-T therapy still requires further observation. But if Carvykti is approved this time, it will also reduce some of the previous concerns about the safety of CAR-T therapy in the market.
The FDA has previously received reports of secondary T-cell malignancies in patients receiving CAR-T therapy and initiated an investigation into this drug category in November 2023.
In January 2024, the FDA requested a black box warning for this type of drug to remind prescribing physicians and patients of these risks.
Earlier this month, the FDA's Oncologic Drugs Advisory Committee (ODAC) supported the approval of Carvykti for earlier-line treatment with a vote of 11-0. Despite the issue of "higher early mortality rates in patients receiving Carvykti treatment" being flagged by FDA's internal reviewers, it still received unanimous support.
This means that the committee believes that the benefits of Carvykti treatment for MM patients, especially those in frontline treatment, far outweigh the risks.
Overall, the imminent approval of Carvykti for second-line MM treatment indications is an uplifting piece of news for Legend Biotech and the entire CAR-T industry