The FDA has approved Roche's Polivy (polatuzumab vedotin) in combination with R-CHP chemotherapy for previously-untreated diffuse large B-cell lymphoma (DLBCL), marking the first new FDA-approved therapy for frontline DLBCL in nearly 20 years. The approval represents a significant milestone for patients with the most common form of non-Hodgkin lymphoma.
Overcoming Initial FDA Concerns
FDA reviewers had initially characterized the drug's benefit as "modest" in the frontline setting. However, the agency's expert advisors subsequently endorsed the treatment at a March meeting, describing its benefits as "clinically meaningful." This shift in perspective ultimately led to the approval despite earlier reservations.
POLARIX Study Results
The approval is supported by the POLARIX study, which demonstrated that the CD79b-directed antibody-drug conjugate (ADC) plus R-CHP achieved a 27% reduction in the risk of disease progression, relapse, or death compared to the standard first-line R-CHOP regimen. While the study showed no statistically significant difference in overall survival, additional follow-up over a median of 40 months confirmed that the improvement in progression-free survival was maintained, with a 24% reduction over the comparator group.
Addressing Critical Unmet Need
The approval addresses a significant clinical challenge in DLBCL treatment. Approximately 40% of people with DLBCL relapse after initial therapy, and for those patients who do relapse, the prognosis is poor with a median overall survival of less than two years. By boosting responses in the front-line setting, Polivy has the potential to provide substantial benefits to patients and reduce the need for later-line therapies.
"It has been nearly 20 years since a new treatment option has become available to people newly diagnosed with diffuse large B-cell lymphoma," commented Roche's chief medical officer, Levi Garraway. The new approval "brings a much-needed new treatment option, which may improve outcomes and bring other benefits to many patients with this aggressive lymphoma."
Global Approval and Commercial Impact
The FDA's positive decision was likely influenced by Polivy's existing approvals alongside R-CHP for previously-untreated DLBCL in more than 60 countries, including EU member states and China. Polivy has been cleared by the FDA since 2019 as a third-line treatment for DLBCL alongside rituximab and bendamustine, but its expansion into first-line use has already resulted in an 85% sales increase to CHF 437 million ($487 million).
Analysts at Jefferies have projected that use in first-line DLBCL could result in peak sales for Polivy of $2.4 billion, highlighting the significant commercial potential of this expanded indication.
NICE Recommendation for NHS Funding
In parallel developments, NICE has recommended regular NHS funding for Polivy in combination with rituximab and bendamustine for adults with DLBCL in second-line treatment when patients cannot have a stem cell transplant. This recommendation overturns a previous rejection following Roche's updated commercial agreement and additional long-term survival analyses.
The NICE recommendation is based on clinical trial evidence showing that Polivy combination treatment caused cancer to become undetectable in approximately 40% of 40 treated patients, compared with around 18% of 40 patients treated with rituximab and bendamustine alone. Around 4,800 people in England have DLBCL, with approximately 530 eligible for this treatment.
Mechanism of Action and Treatment Profile
Polivy is a first-in-class antibody-drug conjugate that targets the CD79b protein expressed on the majority of B-cells that cause non-Hodgkin lymphoma. The drug binds to CD79b and delivers a cytotoxic agent resulting in cell death. The treatment is delivered intravenously every three weeks, with an average course cost of £50,416 at list price, though Roche has offered the NHS a confidential discount.
DLBCL accounts for two in five non-Hodgkin lymphoma cases in the UK and is characterized as an aggressive disease that progresses rapidly, significantly impacting patients' quality of life. The approval of Polivy represents a meaningful advance in treating this challenging malignancy.
