On July 6, 2022 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported that the United States Food and Drug Administration (FDA) has awarded Rare Pediatric Disease Designation (RPDD) to Kazia’s paxalisib for the treatment of atypical rhabdoid / teratoid tumors (AT/RT), a rare and highly-aggressive childhood brain cancer (Press release, Kazia Therapeutics, JUL 6, 2022, View Source [SID1234616497]).

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Key Points

Rare Pediatric Disease Designation (RPDD) is granted to drugs which are under development for rare childhood diseases.

RPDD means that the sponsor may be entitled to receive a pediatric priority review voucher (pPRV) if the drug is initially approved for that rare childhood disease. A PRV grants the holder an expedited six-month review of a new drug application. PRVs are tradeable and have historically commanded prices in excess of US$ 100 million.

FDA’s award of RPDD follows the presentation of promising preclinical data for paxalisib in AT/RT, which was presented by Professor Jeffrey Rubens and colleagues at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans, LA, in April 2022.

Paxalisib was previously granted orphan drug designation (ODD) for AT/RT by FDA on 16 June 2022.

Kazia CEO, Dr James Garner, commented, "this is the second time that paxalisib has been granted RPDD, and it demonstrates the importance of childhood brain cancer in the overall paxalisib development program. Brain cancer is the most common cause of cancer death in children, and outcomes in many forms of childhood brain cancer have not improved in decades. We very much hope that paxalisib can make a difference to families affected by both DIPG and AT/RT, and we will be working closely with clinicians, researchers, and FDA to determine the optimal way to move the drug forward."

Rare Pediatric Disease Designation

The Food and Drug Administration Safety and Innovation Act (2012) established FDA’s RPDD initiative. RPDD may be granted to drugs in development for diseases which primarily affect children (under the age of 18 years), have an incidence of less than 200,000 new cases per annum in the United States, and which are serious or life-threatening.

A sponsor of a drug with RPDD may request a Rare Pediatric Disease Priority Review Voucher (PRV) at the time of a marketing application to FDA. In effect, the PRV shortens the FDA review period for a future marketing application of any drug from 12 months to 6 months. PRVs can be sold to other companies and have historically been transacted at prices in the tens to hundreds of millions of dollars. For a large company launching a billion-dollar drug, the six-month acceleration in regulatory review can be of substantial economic value. In 2019, five pediatric PRVs were granted by FDA.

Next Steps

A phase II clinical trial of multiple drug therapies, including paxalisib, is ongoing, under the sponsorship of the Pacific Pediatric Neuro-Oncology Consortium (PNOC) (NCT05009992). This study combines several investigational drugs in the treatment of patients with diffuse midline gliomas (DMGs), a category which includes DIPG. Initial data from this study is anticipated in CY2023.

A phase I study of paxalisib in DIPG, led by St Jude Children’s Research Hospital in Memphis, TN (NCT03696355), is nearing completion, and final data is expected to be submitted for publication by the end of CY2022.

On July 6, 2022 Cardinal Health (NYSE: CAH) reported that it has acquired the Bendcare group purchasing organization (CPO-GPO) entity and made a minority investment in the Bendcare management services organization (MSO) (Press release, Cardinal Health, JUL 6, 2022, View Source [SID1234616496]). Following the acquisition of the CPO-GPO, current Bendcare-affiliated CPO-GPO members will transition to Cardinal Health’s Cornerstone Rheumatology GPO, and Cardinal Health will be the exclusive distributor for those practices.

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This acquisition demonstrates Cardinal Health’s strategy of prioritizing investment in strategic growth areas and expands distribution opportunities and technology solution offerings for specialty practices. Financial terms of the transaction were not disclosed.

"Bendcare is a leader in delivering real-world technology, specialty practice management and research solutions that empower physicians and patients in the specialty rheumatology market," said Dan Duran, Senior Vice President and General Manager, Provider Solutions, Cardinal Health Specialty Solutions. "We are excited to combine their solutions with our best-in-class distribution to support rheumatology providers so they can ultimately focus on achieving cost-effective patient outcomes and care."

Combining the expertise and capabilities of Cardinal Health and Bendcare together will create an integrated suite of clinical, practice management and distribution solutions to help support the success of rheumatology practices nationwide.

"Rheumatology providers and patients are navigating a number of industry challenges," said Andrew S. Ripps, CEO, Bendcare. "Cardinal Health is an industry leader in distribution and technology solutions. Our synergistic cultures, combined with our service and technology innovation and expertise, will ignite our ability to continue to lead in the rheumatology space as we expand into other specialties and improve patients’ experience, care and value."

Cardinal Health has one of the largest healthcare supply chains in the U.S. with strategically located distribution centers that enable fast and efficient delivery anywhere in the U.S. Through Specialty Solutions, Cardinal Health provides reliable distribution and advanced technology solutions to community-based practices across the nation with specialties in rheumatology, oncology, urology, nephrology, gastroenterology, ophthalmology, neurology, immunology and multi-specialty infusion centers.

On July 6, 2022 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) and granted Priority Review for mosunetuzumab, a potential first-in-class CD20xCD3 T-cell engaging bispecific antibody, for the treatment of adults with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least two prior systemic therapies (Press release, Genentech, JUL 6, 2022, View Source [SID1234616483]). FL is the most common indolent (slow growing) form of non-Hodgkin’s lymphoma (NHL), a type of blood cancer, which often returns after initial therapy. The FDA is expected to make a decision on approval of this novel cancer immunotherapy by December 29, 2022.

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"New therapeutic options are needed for follicular lymphoma, which often relapses after initial therapy and becomes increasingly difficult to treat each time it returns. Clinical trial results have demonstrated durable responses with mosunetuzumab in advanced follicular lymphoma, representing a step toward shifting the treatment paradigm"

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"New therapeutic options are needed for follicular lymphoma, which often relapses after initial therapy and becomes increasingly difficult to treat each time it returns. Clinical trial results have demonstrated durable responses with mosunetuzumab in advanced follicular lymphoma, representing a step toward shifting the treatment paradigm," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "Since mosunetuzumab does not require the collection or genetic modification of patient cells, it could become an effective, fixed-duration outpatient option without the barriers of travelling to a major academic center."

The BLA is based on positive results from the pivotal Phase I/II GO29781 study of mosunetuzumab, which showed high complete response (CR) rates, with the majority of responders (57% [95% CI: 49-70]) maintaining responses for at least 18 months, and manageable tolerability in people with heavily pretreated FL. After a median follow-up of 18.3 months, the CR rate was 60% (n=54/90) and the objective response rate was 80% (n=72/90). The median duration of response among those who responded was 22.8 months (95% CI: 9.7-not estimable). The most common adverse event (AE) was cytokine release syndrome (39%; n=86/218), which was generally low grade (grade 1: 25.6%; grade 2: 14%; grade 3: 2.3%; grade 4: 0.5%), and all events resolved. Other common AEs (>20%) included fatigue, headache, neutropenia, fever and hypophosphatemia. Treatment was administered without mandatory hospitalization. Results were presented for the first time in December 2021 at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition.

Priority Review designation is granted to medicines that the FDA considers to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention or diagnosis of a serious disease. The FDA granted Breakthrough Therapy Designation (BTD) to mosunetuzumab for the treatment of adults with R/R FL who have received at least two prior systemic therapies in June 2020 and Orphan Drug Designation in December 2018. BTD is designed to accelerate the development and review of medicines intended to treat serious or life-threatening conditions with preliminary evidence that indicates they may demonstrate substantial improvement over existing therapies. The European Commission granted conditional marketing authorization for mosunetuzumab for the treatment of people with R/R FL who have received at least two prior systemic therapies in June 2022.

A robust development program for mosunetuzumab is ongoing including two Phase III studies: CELESTIMO investigating mosunetuzumab plus lenalidomide in second-line plus (2L+) FL, and SUNMO, investigating mosunetuzumab plus Polivy (polatuzumab vedotin) in 2L+ diffuse large B-cell lymphoma (DLBCL).

About the GO29781 Study

The GO29781 study [NCT02500407] is a Phase I/II, multicenter, open-label, dose-escalation and expansion study evaluating the safety, efficacy and pharmacokinetics of mosunetuzumab in people with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Outcome measures include complete response rate (best response) by independent review facility (primary endpoint), objective response rate, duration of response, progression-free survival, safety and tolerability (secondary endpoints).

About Follicular Lymphoma

Follicular lymphoma (FL) is the most common slow-growing (indolent) form of non-Hodgkin’s lymphoma, accounting for about one in five cases. It typically responds well to treatment but is often characterized by periods of remission and relapse. The disease typically becomes harder to treat each time a patient relapses, and early progression can be associated with poor long-term prognosis. In the United States, it is estimated that approximately 13,000 new cases of FL will be diagnosed in 2022.

About Mosunetuzumab

Mosunetuzumab is a first-in-class CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. A robust clinical development program for mosunetuzumab is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin’s lymphomas, including follicular lymphoma, diffuse large B-cell lymphoma and other blood cancers.

About Polivy (polatuzumab vedotin-piiq)

Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B cells, an immune cell impacted in some types of non-Hodgkin’s lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells. Polivy is being developed by Genentech using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.

Polivy U.S. Indication

Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat diffuse large B-cell lymphoma in adults who have progressed after at least two prior therapies.

The accelerated approval of Polivy is based on a type of response rate. There are ongoing studies to confirm the clinical benefit of Polivy.

Important Safety Information

Possible serious side effects

Everyone reacts differently to Polivy therapy, so it’s important to know what the side effects are. Some people who have been treated with Polivy have experienced serious to fatal side effects. A patient’s doctor may stop or adjust a patient’s treatment if any serious side effects occur. Patients must contact their healthcare team if there are any signs of these side effects.

Nerve problems in arms and legs: This may happen as early as after the first dose and may worsen with every dose. If a patient already has nerve pain, Polivy may make it worse. The patient’s doctor will monitor for signs and symptoms, such as changes in sense of touch, numbness or tingling in hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to walking patterns
Infusion-related reactions: A patient may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of the infusion
Infections: Patients should contact their healthcare team if they experience a fever of 100.4°F or higher, chills, cough, or pain during urination. Also, a patient’s doctor may give medication before giving Polivy, which may prevent some infections, and monitor blood counts throughout treatment with Polivy. Treatment with Polivy can cause severe low blood cell counts
Rare and serious brain infections: A patient’s doctor will monitor the patient closely for signs and symptoms of these types of infections. Patients should contact their doctor if they experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes
Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy
Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of the skin or the white part of the eyes. Patients may be at higher risk if they already have liver problems or are taking other medication
Side effects seen most often

The most common side effects during treatment were:

Low blood cell counts (platelets, red blood cells, white blood cells)
Nerve problems in arms and legs
Tiredness or lack of energy
Diarrhea
Nausea
Fever
Decreased appetite
Infections
Polivy may not be for everyone. A patient should talk to their doctor if they are:

Pregnant or may be pregnant: Data have shown that Polivy may harm an unborn baby
Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for at least 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for at least 5 months after their last Polivy treatment
Breastfeeding: Women should not breastfeed while taking Polivy and for at least 2 months after the last dose
These may not be all the side effects. Patients should talk to their healthcare provider for more information about the benefits and risks of Polivy treatment.

On July 5, 2022 Defence Therapeutics Inc. ("Defence" or the "Company"), a Canadian biopharmaceutical company specialized in the development of immuneoncology vaccines and drug delivery technologies, is pleased to reported an update on its ADC programsin development using Defence’s AccumTM, including key in vivo studies with worldwide collaborators (Press release, Defence Therapeutics, JUL 5, 2022, View Source [SID1234626251]).

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The world-renowned Curie Institute, one of Defence’s collaborator, is currently performing therapeutic efficacy study of AccumTM-T-DM1 Antibody Drug Conjugate ("ADC") in patientderived xenograft ("PDX") model of breast cancer, including in 3 HER2+ and in 1 triple-negative PDX. It will be immediately followed by a head-to-head toxicology and pharmacokinetic profile comparisons study of T-DM1 versus AccumTM T-DM1 in mice. Results are expected in Q3-Q4 of this year. T-DM1 (Kadcyla) is currently used to treat women with metastatic HER2-positive breast cancer. This study is to prove that the current treatment may be optimized using Defence’s AccumTM technology to enhance the drug delivery to the tumor cells. Estimated sales of Kadcyla in 2022 are $3.02 Billion USD.

Defence is continuing its collaboration with the HUS Comprehensive Cancer Center, Finland’s largest and most versatile cancer treatment center, which is currently performing advanced in vivo studies, including head-to-head comparisons of T-DM1 vs AccumTM-T-DM1 vs co-treatment with intratumorally injection of AccuTOXTM variants using different PDX models with established and non-established tumors. Linking the AccumTM to an ADC triggers endosomal escape increasing therefore ADCs intracellular accumulation and cytotoxicity potency. AccuTOXTM variants induce cancer cell death through ROS production and endosome rupture. Results of those key studies with HUS are expected in Q4 of this year.

The Institut de Recherche en Cancérologie de Montpellier (IRCM), an internationally recognized institute for its translational research and expertise’s in immunotherapy and radiotherapy, is currently performing in vivo studies using AccumTM with radio-immuno-therapeutic conjugates. Combining the AccumTM technology to the radio-immuno-conjugate is expected to amplify the therapeutic index of the drug while minimizing side effects observed in patients undergoing the therapy. Results of those studies with IRCM are expected to be known in Q3-Q4 of 2022. The Radiopharmaceuticals Market is projected to reach US$ 13.818 billion by 2028 from US$ 7.55 billion in 2021; it is expected to grow at a CAGR of 9.0% during 2021–2028.

Defence is also collaborating with WASSC Technologies, a biotech company specialized in protein conjugations, small molecules, and ADCs, to develop a new small molecule for ADC application. Toxicity results of variants are expected for Q3 of 2022 and antibody conjugation shall begin in Q4 of 2022.

"Defence’s AccumTM platform has been primarily developed and tested in vitro and in vivo to enhance the intranuclear drug delivery on multiple FDA approved antibody-conjugates or new conjugates under development. We strongly believe that all those key results coming this year related to AccumTM-ADCs will continue to demonstrate the potency of our AccumTM technology and bring Defence to another level", says Mr. Sebastien Plouffe, the CEO of Defence Therapeutics

On July 5, 2022 Nordic Nanovector ASA (OSE: NANOV) reported an update on PARADIGME, its Phase 2b trial of Betalutin (177Lu lilotomab satetraxetan) in 3rd-line relapsed and anti-CD20 refractory follicular lymphoma (3L R and R FL) (Press release, Nordic Nanovector, JUL 5, 2022, View Source [SID1234616506]). Following a comprehensive review and independent data evaluation of PARADIGME and a subsequent request for regulatory agency interaction, the Board of Directors (Board) has taken the difficult decision to discontinue the study. No further patients will be enrolled into PARADIGME.

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The PARADIGME trial enrolled a total of 109 patients. The Company will now ensure a wind-down of PARADIGME in a structured manner ensuring patients receive the best possible care during this period.

While Betalutin, at the selected dose of 15 MBq/kg after a pre-dose of 40 mg lilotomab (40/15), has continued to display an attractive safety profile and positive signs of efficacy in some patients, the Board considers that the observed profile does not fully meet the objectives set out for the PARADIGME study. Only one out of three patients responded to the treatment with the average duration of the response of approximately six months. As a result, the Board is of the opinion that the demonstrated profile is no longer sufficiently competitive to bring Betalutin to the market in the third line relapsed and refractory FL indication, within a timeframe that makes financial and commercial sense for the Company.

The Company still believes there could be a market for Betalutin in light of its safety profile, promising efficacy in earlier lines of therapy and unique feature of being delivered as a one-time dose. However, a potential new development programme would need to be conducted in a different patient population and line of treatment. The Company will therefore explore potential partnerships and will also seek advice from the US Food and Drug Administration (FDA) to discuss if there could be a possible way forward for Betalutin in an alternative setting.

The Company will now focus its efforts and resources on developing its pipeline of proprietary CD37-targeting products from which Nordic Nanovector believes it can create value for shareholders over the longer term. These pipeline opportunities include:

Humalutin, a radioimmunotherapy candidate based on a chimeric anti-CD37 antibody and the beta-emitting radionuclide lutetium-177 for non-Hodgkin lymphoma (NHL).
Alpha37, an alpha-emitting radioimmunotherapy candidate based on a chimeric anti-CD37 antibody conjugated to lead-212, currently being explored with partner OranoMed for relapsed/refractory chronic lymphocytic leukaemia.
A portfolio of fully humanized anti-CD37 antibodies with potential in haematological cancers and autoimmune diseases.
A CD37 DOTA CAR-T cell opportunity in haematological cancers, which is the subject of a research collaboration with the University of Pennsylvania.
Following the decision to discontinue PARADIGME, the Board has also decided to implement a restructuring of the Company with immediate effect with the purpose of reducing costs where necessary to enable support of essential activities associated with development of the pipeline.

The Company’s cash position at the end of Q2 2022 was approximately NOK 280m (end of Q1 NOK 356.3m). Full Q2 results will now be reported on 31 August.

Chairman, Jan H. Egberts commented: "The decision to discontinue PARADIGME is extremely disappointing not only for the Nordic Nanovector team, but also for patients, healthcare providers and our shareholders as there continues to be an unmet medical need in frail and elderly patients with Follicular Lymphoma. The new independently reviewed data from PARADIGME, in an increasingly competitive market and with the slow speed of recruitment makes progressing PARADIGME further very difficult. Consequently, the Board no longer sees a viable path to commercialisation in the current indication that would make sense for the Company and its shareholders. We are extremely grateful to all the clinical investigators and patients who have participated in PARADIGME.

CEO, Erik Skullerud commented: Our focus will now shift to our pipeline of other CD37-targeting assets, which give us multiple shots on goal, including Humalutin, Alpha37, a portfolio of fully humanized anti-CD37 antibodies and the CD37 CAR-T. We look forward to communicating our development plans for these assets in more detail in the coming months."

Nordic Nanovector will host a webcast at 08.30 CEST on Wednesday 6 July, elaborating on the strategic decision to stop PARADIGME and including a Q&A session. To join the webcast please sign up via our website www.nordicnanovector.com.