Janssen Marks First Approval Worldwide for AKEEGA® (Niraparib and Abiraterone Acetate Dual Action Tablet)

The Janssen Pharmaceutical Companies of Johnson & Johnson announced that the European Commission (EC) had granted marketing authorization for AKEEGA® (niraparib and abiraterone acetate [AA]), in the form of a dual-action tablet (DAT) given in combination with prednisone or prednisolone, for the treatment of adults with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2 mutations (germline and somatic) in whom chemotherapy is not clinically indicated.

Prostate cancer is the most common cancer in men in Europe and the sixth leading cause of cancer-related mortality worldwide. Despite advancements in treatment, mCRPC remains an incurable and fatal disease. BRCA1/2 gene mutations have been detected in roughly 10-15% of mCRPC patients and are more likely to induce aggressive disease, poor prognosis, and a shorter survival period.

Metastatic castration-resistant prostate cancer remains a lethal disease, with high unmet needs in terms of treatment options, particularly for patients with BRCA1/2 gene mutations. We found that niraparib combined with abiraterone acetate and predniso(lo)ne (AAP) significantly reduced the risk of disease progression or death in these patients when compared to AAP.” Niraparib in combination with abiraterone acetate is a viable first-line targeted therapy option for males with mCRPC and BRCA1/2 mutations.

Professor Gerhardt Attard, Oncologist, University College London (UCL), London, UK

The EC approval, which also marks the first international approval for AKEEGA®, is based on the findings of the randomised, double-blind, placebo-controlled Phase III MAGNITUDE study (NCT03748641).11 The experiment looked at whether adding niraparib to AAP improved outcomes in people with untreated mCRPC, with or without changes in homologous recombination repair (HRR) related genes (which are involved in the repair of damaged DNA), such as BRCA1/2.1.14 A total of 423 individuals with HRR gene changes were enrolled, with 225 (53.2%) having BRCA mutations, making it the largest cohort of BRCA1/2-positive patients with first-line mCRPC in any clinical research to date.

FDA Approves Roche’s Polivy Combo for Frontline B-cell Lymphoma

Roche announced that the U.S. Food and Drug Administration (FDA) had approved Polivy® (polatuzumab vedotin-piiq) in combination with Rituxan® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) for the treatment of adult patients who have previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index (IPI) score of two or greater. This FDA decision transforms Polivy’s accelerated approval in combination with bendamustine and Rituxan for R/R DLBCL after at least two prior regimens to regular approval.

DLBCL is the most common type of non-Hodgkin lymphoma in the United States and is an aggressive, difficult-to-treat cancer. In the United States, around 31,000 persons are expected to be diagnosed with DLBCL by 2023. Over the last two decades, there has been little progress in improving patient outcomes in previously untreated DLBCL. While many patients react to initial treatment, up to four out of every ten people with DLBCL do not respond or relapse. Most relapses occur within two years of starting treatment with the standard of care, MabThera/Rituxan plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), and the majority of those who require subsequent lines of therapy have poor outcomes.

It has been nearly 20 years since a new treatment option has become available to people newly diagnosed with diffuse large B-cell lymphoma. Today’s FDA approval of Polivy in combination with R-CHP in this setting provides a much-needed new treatment option that may improve outcomes and bring other benefits to many patients with this aggressive lymphoma.

Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development at Roche

The FDA approved Polivy plus R-CHP for the first-line treatment of DLBCL based on pivotal data from POLARIX, an international phase III, randomised, double-blind, placebo-controlled study that demonstrated a statistically significant and clinically meaningful improvement in PFS compared to R-CHOP.

Roche is continuing to investigate areas of unmet need where Polivy has the potential to provide further benefit, including ongoing studies combining Polivy with the company’s CD20xCD3 T-cell engaging bispecific antibodies Lunsumio® (mosunetuzumab) or Columvi® (glofitamab). Trials include the phase III SUNMO trial with Lunsumio in patients with R/R DLBCL and the phase III POLARGO study with MabThera/Rituxan in combination with gemcitabine and oxaliplatin in patients with R/R DLBCL.

FDA Extends Review Period for Quizartinib for Adults With FLT3-ITD-Positive AML

Daiichi Sankyo announced that the New Drug Application for quizartinib, intended for the treatment of adult patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia (AML), has had its review period extended by the U.S. Food and Drug Administration. The application includes the use of quizartinib in combination with standard cytarabine and anthracycline induction, as well as standard cytarabine consolidation chemotherapy and continuation monotherapy following consolidation.

To review the proposed Risk Evaluation and Mitigation Strategies (REMS) included in an application, the FDA has extended the Prescription Drug User Fee Act action date by three months until July 24, 2023. The extension was necessary to allow additional time for the review of requested updates. All efficacy and safety data have been requested as part of the review process.

Mark Rutstein, MD, Global Head of Oncology Clinical Development at Daiichi Sankyo, stated that they are actively collaborating with the FDA to expedite the review of the quizartinib new drug application, with the ultimate goal of making this vital medication available to patients as soon as possible. Quizartinib has the potential to revolutionize the treatment of patients with newly diagnosed FLT3-ITD positive AML by enhancing overall survival when added to standard chemotherapy and continued as monotherapy.

The NDA submission is founded on the findings from the QuANTUM-First study, which revealed that the use of quizartinib in combination with standard cytarabine and anthracycline induction, standard cytarabine consolidation chemotherapy, and monotherapy following consolidation, led to a significant improvement in overall survival among adult patients with newly diagnosed FLT3-ITD positive AML compared to chemotherapy alone. The results of QuANTUM-First were presented at the 2022 European Hematology Association (EHA) Congress and were deemed both statistically significant and clinically meaningful.

During the QuANTUM-First study, the safety profile of quizartinib in combination with intensive chemotherapy and as continuation monotherapy was found to be generally manageable, and there were no reports of any new safety concerns. The frequency of QT prolongation events of grade ≥3 was low, and there were a few unique ventricular arrhythmia events. However, the risk of QT prolongation was manageable through ECG monitoring, modifying the dosage of quizartinib, and addressing or eliminating any additional risk factors.

bluebird bio Submits BLA to FDA for lovo-cel for Patients with Sickle Cell Disease 12 years and Older

bluebird bio, Inc. has announced the submission of its Biologics License Application to the U.S. Food and Drug Administration for the use of lovotibeglogene autotemcel (lovo-cel) gene therapy in patients aged 12 and above with sickle cell disease (SCD) who have a history of vaso-occlusive events (VOEs). The BLA submission includes a request for Priority Review, which, if granted, would accelerate the FDA’s review process from the usual 10 months to only 6 months from the time of filing. If approved, lovo-cel would become bluebird bio’s third ex-vivo gene therapy to receive FDA approval for treating a rare genetic disease and its second approval for treating an inherited hemoglobin disorder, marking over a decade of leadership in gene therapy.

Sickle cell disease has been neglected for a long time, and the suffering of patients and caregivers is not fully acknowledged. He added that transformational therapies are much needed for this community. He further stated that the company is glad to have addressed the FDA’s concerns regarding comparability, and they have taken a significant step towards making lovo-cel accessible to individuals with SCD.

Andrew Obenshain, CEO of bluebird bio

Among gene therapies being developed for sickle cell disease, lovo-cel is the most extensively studied. The submission of the BLA is anchored on efficacy results from 36 patients in the HGB-206 Group C cohort, with a median follow-up of 32 months, and two patients in the HGB-210 study, each with 18 months of follow-up. Additionally, the BLA includes safety data from the entire lovo-cel program, covering 50 patients treated in total, including six patients with a follow-up of six or more years.

For the treatment of sickle cell disease (SCD), lovo-cel has been granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation, and rare pediatric disease designation by the FDA.

Lantheus and POINT Biopharma Announce FDA Grants Fast Track Designation for ¹⁷⁷Lu-PNT2002 for the Treatment of Metastatic Castration-Resistant Prostate Cancer

On April 24, 2023, Lantheus Holdings, Inc. (“Lantheus”) (NASDAQ: LNTH) and POINT Biopharma Global, Inc. (“POINT”) (NASDAQ: PNT) announced the U.S. Food and Drug Administration (FDA) had granted Fast Track designation for 177Lu-PNT2002 for the treatment of metastatic castration-resistant prostate cancer (mCRPC). PNT2002 is an innovative PSMA-targeted 177Lu-based radiopharmaceutical therapy that combines a PSMA-targeted ligand, PSMA-I&T, with the beta-emitting radioisotope no-carrier-added 177Lu. Lantheus in-licensed exclusive worldwide commercialization rights (excluding certain Asian territories) to 177Lu-PNT2002 from POINT in December 2022. 

“Fast track designation by the FDA is an important milestone and recognizes the potential for 177Lu-PNT2002 to address the significant unmet need for mCRPC patients. We are encouraged by the FDA’s decision as it reflects the need for FDA approved and widely available treatments for these patients. This designation will allow us to work closely with the FDA, along with our partner POINT, to quickly advance 177Lu-PNT2002, with the potential to make a meaningful difference for patients who require new treatment options.” 

Jean-Claude Provost, M.D., Chief Medical Officer at Lantheus

The FDA Fast Track designation for 177Lu-PNT2002 underscores its potential to address a serious unmet need and serve as a meaningful therapeutic option for patients with mCRPC. We are seeing that radioligand therapy is quickly becoming another pillar of cancer treatment, and, with our continued focus on supply chain excellence, we believe that we are very well positioned to meet market demands post approval. We will continue to work closely with our partner Lantheus and with the FDA to bring 177Lu-PNT2002 to patients as quickly as possible.

Dr. Neil Fleshner, M.D., Chief Medical Officer of POINT Biopharma.

The Phase 3 SPLASH trial is a multicenter, randomized, open-label assessment of 177Lu-PNT2002 in participants with PSMA-expressing mCRPC who have progressed to androgen receptor pathway inhibitor therapy and refuse or are not eligible for chemotherapy. Participants were randomized 2:1, with those in arm A receiving 177Lu-PNT2002 and those in arm B receiving either abiraterone or enzalutamide. 

Participants in arm B who experience centrally assessed radiographic progression and meet protocol eligibility have the option to crossover and receive 177Lu-PNT2002. Patients are subject to follow-up for up to 5 years from their first 177Lu-PNT2002 dose. The primary endpoint of the study is radiographic progression-free survival. Key secondary endpoints include overall survival, overall response rate, and duration of response. Safety and tolerability will also be assessed. As per the update from Lantheus Holdings, Inc., the enrollment in the trial is complete, and SPLASH top-line data is expected in the second half of 2023. 

Prostate Cancer represents a very high socioeconomic burden. As per the DelveInsight’s assessment, the total prevalent cases of prostate cancer in the 7MM were observed to be around 7 million cases in 2022. Among the 7MM, the US accounted for the highest number of cases, which were approximately 3 million cases in 2022. Moreover, the total diagnosed prevalent cases of mCRPC in the were observed to 90,000 in the 7MM in 2022. The cases in the 7MM are expected to increase in the coming years. Several pharma and biotech companies such as Lantheus Holdings, Inc, Surface Oncology, Regeneron, Clovis Oncology, AstraZeneca, Pfizer, among others are actively working in the mCRPC therapeutics market. 

XORTX Announces Receipt of FDA Orphan Drug Designation to Treat Autosomal Dominant Polycystic Kidney Disease

On April 21, 2023, XORTX Therapeutics Inc. announced the grant of Orphan Drug Designation for oxypurinol. XORTX’s Oxypurinol is a xanthine oxidase inhibitor (“XOI”) with meaningful pharmacologic characteristics ideal for administration to individuals with ADPKD. Oxypurinol has the ability to act in the circulation, kidney and cardiovascular tissue and inhibit the production of uric acid and so attenuate the mechanism of injury and accelerating effect of xanthine oxidase on progressing diseases. The FDA ODD office review of the application package provided by XORTX determined that the evidence that aberrant purine metabolism and high uric acid levels suggest a mechanism of injury in ADPKD and importantly, that the XORLOTM therapy may slow progression of this form of injury.

Moreover, as per the update from XORTX, the XORLOTM provides substantially increased absorption of oxypurinol. This approach provides an effective, well-tolerated drug with extensive clinical safety experience, suggesting the Company’s XRx-008 program has the capacity to provide superior XOI to slow the accelerating decline in kidney function during ADPKD progression.

Orphan drug designation represents a major milestone for the Company in pursuit of marketing approval for XORLOTM, our proprietary formulation of oxypurinol, and the XRx-008 program for ADPKD. This designation was a significant and critical milestone for all of the staff and management at the Company. Further, our potential partners indicated that it was a critical requirement underpinning their ongoing consideration of the XORLOTM program. We look forward to our upcoming meeting with the FDA on May 1, 2023, to discuss our planned phase 3 clinical program for XORLOTM.

Allen Davidoff, CEO XORLOTM

XORTX recently presented positive results in animal models of PKD in both mice and rats, showing the ability of XORTX’s proprietary formulation of oxypurinol, XORLOTM, to attenuate expansion of kidneys due to the cyst-promoting effects of aberrant purine metabolism and hyperuricemia – at the American Society of Nephrology meeting during the November 2022 meeting.
As per DelveInsight, the total diagnosed prevalent cases of Autosomal Dominant Polycystic Kidney Disease in the 7MM were found to be approximately 367,000+ in the year 2021. The diagnosed prevalent cases of Autosomal Dominant Polycystic Kidney Disease are likely to increase in the coming years. To provide effective therapeutics option, globally several major pharmaceutical companies are actively working in the domain. The ongoing clinical trial activities raise high hope for better treatment option in the Autosomal Dominant Polycystic Kidney Disease market in the near future.