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Sunday, December 6, 2020

Biotech week ahead, Dec. 7

Biotech stocks headed higher in the week ended Dec. 5 as broader market optimism pervaded into the sector. The sector also continued to get support from vaccine-related positive news flow.

The biggest headline of the week was the first-ever emergency-use authorization of a coronavirus vaccine candidate. The U.K. became the first country to conditionally approve a vaccine, as the nation's regulator gave its nod to Pfizer Inc. PFE 0.65% and BioNTech SE – ADR BNTX 1.11% for their mRNA vaccine, BNT162b2. The timeline for authorizations elsewhere has also been set.

Moderna Inc MRNA 3.24% reported at the start of the week positive primary efficacy and safety data, and also filed for emergency use authorization with the U.S. Food and Drug Administration.

Meanwhile, Novavax, Inc. NVAX 2.25% hinted at a delay in the U.S. leg of the Phase 3 study of its vaccine candidate. And Inovio Pharmaceuticals Inc INO 0.64%, which also is working on a vaccine, added a new contract development and manufacturing organization (CDMO) to its consortium of partners.

The two FDA decisions slated for the week led to positive results, with the agency approving Vanda Pharmaceuticals Inc.'s VNDA 2.06% sleep disorder drug and BioCryst Pharmaceuticals, Inc.'s BCRX 18.79% treatment for hereditary angioedema.

The week also witnessed multiple presentations at the virtual American Society of Hematology annual meeting.

Four biotechs made their Wall Street debuts this week, raising a combined $782.5 billion in gross proceeds from initial public offerings.

Here are the key catalysts for the upcoming week:

FDA Meeting On Pfizer-BioNTech Vaccine

The FDA's Vaccines and Related Biological Products Advisory Committee will meet Dec. 10 (Thursday) in an open session to discuss emergency use authorization of the vaccine developed by Pfizer and BioNTech. This is one of the most highly anticipated points in the timeline of this unfolding COVID-19 vaccine saga. It could determine whether some Americans start getting vaccines as soon as the next day. Vaccinations are set to begin in the U.K. on Tuesday.

Conferences

American Epilepsy Society, or AES, Annual Meeting (virtual event): Dec. 4-8
62nd American Society of Hematology, or ASH, Annual Meeting and Exposition virtual event: Dec. 5-8
San Antonio Breast Cancer Symposium, or SABCS, being held virtually: December 8-11
ESMO Immuno-oncology Virtual Congress: Dec. 9-12

Clinical Readouts/Presentations

Sarepta Therapeutics Inc SRPT 3.13% will present on Monday interim data from the MOMENTUM study, a multiple-ascending dose clinical trial of SRP-5051, for the treatment of Duchenne muscular dystrophy.

ASH Conference Presentations

Sunday

Erytech Pharma SA ERYP 3.48%: results of Phase 2 trial of eryaspase in acute lymphoblastic leukemia patients

Imara Inc IMRA 1.51%: data from the ongoing IMR-687 Phase 2a open label extension clinical trial in adult patients with sickle cell disease

Blueprint Medicines Corp BPMC 3.1%: Overall survival data in patients with advanced systemic mastocytosis receiving avapritinib in the Phase I EXPLORER study

Protagonist Therapeutics Inc PTGX 5.19%: updated results from the Phase 2 proof-of-concept study of PTG-300 in polycythemia vera

Xencor Inc XNCR 0.82%: Updated results from Phase 1 studies of vibecotamab in acute myeloid leukemia

Rocket Pharmaceuticals Inc RCKT 4.95%: Phase 1 study of lentiviral mediated gene therapy for pyruvate kinase deficiency

Beigene Ltd BGNE 0.71%: initial results from the MAGNOLIA Phase 2 trial of zanubrutinib in patients with relapsed/refractory marginal zone lymphoma

MacroGenics Inc MGNX 6.24%: Phase 1/2 data for flotetuzumab in primary induction failure and early relapse acute myeloid leukemia

Vertex Pharmaceuticals Incorporated VRTX 0.64% & Crispr Therapeutics AG CRSP 5.04%: results from two ongoing Phase 1/2 clinical trials of the investigational CRISPR/Cas9 gene-editing therapy CTX001 in patients with sickle cell disease and beta thalassemia.

ADC Therapeutics SA ADCT 0.87%: preliminary results of a Phase 2 study of camidanlumab tesirine (Cami), an antibody-drug conjugate, in patients with relapsed or refractory Hodgkin lymphoma; interim results of loncastuximab tesirine combined with ibrutinib in relapsed/refractory diffuse large B-cell lymphoma

Syndax Pharmaceuticals Inc SNDX 1.78%: updated data from the Phase 1 trial of axatilimab, its anti-CSF-1R monoclonal antibody, in patients with chronic graft versus host disease

CTI BioPharma Corp CTIC: results from the Phase 1/2 study of pacritinib in graft-versus-host disease

Aptose Biosciences Inc APTO 3.01%: data from the Phase 1a/b dose escalation study of CG-806 in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma or Non-Hodgkin's Lymphomas

Johnson & Johnson JNJ 0.82% & Halozyme Therapeutics, Inc. HALO 2.27%: primary data from the Phase 3 APOLLO study of subcutaneous daratumumab in combination with pomalidomide and dexamethasone in patients with multiple myeloma who have received one or more prior lines of therapy

Humanigen Inc HGEN 5.81%: results from the Phase 1/2 multi-center study of lenzilumab and axicabtagene ciloleucel in patients with relapsed or refractory large B cell lymphoma

Imv Inc IMV 1.14%: updated data from phase 2 SPiReL study evaluating IMV's T cell therapy - DPX-Survivac - in combination with Merck & Co., Inc.'s MRK 0.61% Keytruda in patients with relapsed / refractory diffuse large B cell lymphoma

Monday

Bluebird bio Inc BLUE 0.13%: updated results from patients in Group C of the Phase 1/2 HGB-206 study of lentiGlobin for sickle cell disease gene therapy

Rocket Pharmaceuticals: Phase 1/2 study of lentiviral-mediated ex-vivo gene therapy for pediatric patients with severe leukocyte adhesion deficiency-I and updated results from global clinical studies of RP-L102 in Fanconi anemia

Beigene: data from the Phase 2 study of zanubrutinib in patients with Waldenström macroglobulinemia as well as Phase 2 study of zanubrutinib in patients with relapsed/refractory B-cell malignancies

Sutro Biopharma Inc STRO 33.24%: additional Phase 1 dose-escalation data for STRO-001 in patients with B-cell non-Hodgkin lymphoma

Precigen Inc PGEN 0.06%: initial Phase 1 data for PRGN-3006 in myelodysplastic syndromes and acute myeloid leukemia

Forma Therapeutics Holdings Inc FMTX 0.07%: data from the Phase 1 study of FT-4202 in patients with Sickle Cell Disease

Autolus Therapeutics PLC AUTL 0.57%: longer term follow-up data for AUTO1 in acute lymphoblastic leukemia, and updated Phase 2 data and longer-term follow up data for AUTO3 in diffuse large B cell lymphoma

Curis, Inc. CRIS 6%: results (pharmacokinetics and activity) from the Phase 1 study of CA-4948 in patient with relapsed or refractory hematologic malignancies, and results from the Phase 1 open-label dose escalation trial evaluating CA-4948 in patients with acute myelogenous leukemia or myelodysplastic syndrome

TG Therapeutics Inc common stock TGTX 3.06%: results from the Phase 3 UNITY-CLL study of umbralisib plus ublituximab in patients with treatment naïve and relapsed/refractory chronic lymphocytic leukemia, and results from the Phase 2 global UNITY-NHL trial that is evaluating umbralisib in patients with relapsed or refractory indolent non-Hodgkin's lymphoma

Agios Pharmaceuticals Inc AGIO 1.22%: Phase 1 multiple ascending dose study data for mitapivat in subjects with sickle cell disease

Orchard Therapeutics PLC – ADR ORTX 2.14%: data from the first patient treated in the proof-of-concept study of OTL-201, an investigational ex vivo autologous hematopoietic stem cell gene therapy being studied for the treatment of mucopolysaccharidosis type IIIA

Trillium Therapeutics Inc TRIL 5.8%: updates from Phase 1 dose escalation and expansion study of TTI-621, a biologic targeting CD47, in patients with relapsed or refractory hematologic malignancies

Allovir Inc ALVR 6.22%: results from a Phase 2 study of ALVR106 for treating severe, drug-refractory viral infections in patients following hematopoietic stem cell transplantation

GlycoMimetics Inc GLYC 2.47% and Pfizer: Phase 3 data for rivipansel in vaso-occlusive crisis of sickle cell disease

Alexion Pharmaceuticals, Inc. ALXN 0.45% and Fortress Biotech FBIO 1.83%: Phase 2 dose selection study data for CAEL-101 in patients with AL amyloidosis

Oncternal Therapeutics Inc ONCT 4.72%: data update for patients with mantle cell lymphoma and chronic lymphocytic leukemia, treated with cirmtuzumab plus ibrutinib in a Phase 1/2 study

Tuesday

Uniqure NV QURE 0.79%: first data from the Phase 3 HOPE-B gene therapy trial evaluating efficacy and safety of Etranacogene Dezaparvovec, a AAV5-Padua hFIX variant and codenamed AMT-061, in adults with severe or moderate-severe hemophilia B treated irrespective of pre-existing anti-capsid neutralizing antibodies (11:45 am ET)

SABCS Presentations

Infinity Pharmaceuticals Inc. INFI 0.69% and Arcus Biosciences Inc RCUS 3.64%: Efficacy and safety of Arcus' etrumadenant + pegylated liposomal doxorubicin ± Infinity's eganelisib in participants with metastatic ovarian and triple negative breast cancer (Wednesday, 2 a.m. ET)

Infinity Pharma: Poster presentation on initial Phase 2 data from the study evaluating a triple combo of Infinity's eganelisib, Roche Holdings AG's Basel ADR Common Stock RHHBY 2.2% Tecentriq and Bristol-Myers Squibb Co BMY 0.86% chemotherapy medication Arabaxane as first-line therapy for locally advanced or metastatic triple-negative breast cancer (Wednesday, 2 a.m. ET)

Evelo Biosciences Inc EVLO 4.18%: Poster presentation of additional data from Phase 1/2 trial of EDP1503 in triple-negative breast cancer

Athenex Inc ATNX 2.28%: Phase 2 data for oral Paclitaxel and Encequidar in the treatment of cutaneous angiosarcoma, the breast angiosarcoma group

Incyte Corporation INCY 0.29% & Oncolytics Biotech, Inc. ONCY 11.02%: poster presentation of phase 2 data for Incyte's retifanlimab and the oncolytic virus pelareorep in metastatic triple negative breast cancer (Wednesday, 9 a.m. ET)

Oncolytics Biotech: Phase 2 study to assess overall response rate by inducing an inflammatory phenotype in metastatic breast cancer with the oncolytic reovirus pelareorep in combination with anti-PD-L1 avelumab and paclitaxel

G1 Therapeutics Inc GTHX 4.99%: final analysis of Phase 2 data for trilaciclib in combination of gemcitabine/carboplatin in patients with metastatic triple-negative breast cancer (Wednesday, 10 a.m. to 11:15 a.m.)

Puma Biotechnology Inc PBYI 5.03%: Latest findings from the breast cancer cohort in the SUMMIT Phase 2 study of 'basket' trial of neratinib + trastuzumab + fulvestrant for HER2-mutant, HR-positive, metastatic breast cancer; Final overall survival analysis from the phase 3 study of neratinib in patients with HER2-positive early-stage breast cancer (both on Wednesday)

ESMO Presentations

Innate Pharma SA IPHA 7.16%: updated results from a Phase 2 study investigating the combination of monalizumab and cetuximab in patients with recurrent or metastatic head and neck squamous cell cancer (Wednesday)

Earnings

Veru Inc VERU 0.61% (Wednesday, before the market open)
Enzo Biochem, Inc. ENZ 10.5% (Wednesday, after the close)

https://www.benzinga.com/general/biotech/20/12/18663084/week-ahead-in-biotech-fda-to-decide-on-emergency-use-of-pfizers-covid-vaccine-hematology-conferen

What's new at San Antonio Breast Cancer Symposium this year

The "hottest" presentation at the upcoming 2020 San Antonio Breast Cancer Symposium (SABCS) comes from RxPONDER (abstract GS3-00), a major randomized clinical trial assessing use of a recurrence score among women with lymph node-positive, early-stage breast cancer to determine who might safely forgo chemotherapy.

That's the word from Virginia Kaklamani, MD, from the University of Texas Health Sciences Center San Antonio. Kaklamani, a professor of medicine in the Division of Hematology/Oncology, is co-director of the meeting that runs online December 8-11.

If the new trial sounds familiar, that's because it's a lot like the TAILORx trial, the results of which were first presented in 2018 and have changed practice in women with early-stage disease and no lymph node involvement.

"This is the lymph-node positive TAILORx. It's extremely important," Kaklamani told Medscape Medical News, adding that both trials involved women with HR-positive, HER2-negative disease.

If the RxPONDER trial, she explained, shows similar outcomes between women randomized to adjuvant endocrine therapy alone vs endocrine therapy plus chemotherapy, then clinicians "can potentially avoid giving chemotherapy to a large number of women who are currently receiving it."

Because women with nodal involvement (one to three positive axillary nodes) are at a higher risk of recurrence, RxPONDER may provide needed insight on the management of these types of breast cancers, Kaklamani suggested.

Both trials have used the 21-tumor gene expression assay (Oncotype Dx) to determine recurrence-risk status.

Kaklamani also spotlighted the phase 3 CONTESSA trial (abstract GS4-01) in 600+ patients with locally advanced or metastatic breast cancer that is HR-positive and HER2-negative and has been previously treated with a taxane.

The trial features an experimental oral taxane, tesetaxel. The primary objective is to compare the efficacy of tesetaxel plus a reduced dose of capecitabine (Xeloda) vs the approved dose of capecitabine alone. Presented data will include progression-free survival (PFS) results, indicating about a 3-month PFS advantage with tesetaxel, which is taken once every 3 weeks.

"Oral drugs are convenient for patients and, despite limitations, they are, all in all, a revolution in cancer treatment," noted Kaklamani, adding that they beneficially eliminate the need for time-consuming infusions and related clinic visits as well as drug ports.

It will be interesting to see what Steven Vogl, MD, a private practitioner in the Bronx, New York City, has to say about CONTESSA and the rest of the SABCS.

He is usually a commentator from the meeting floor, whose self-introduction, "Vogl, New York," is well-known to perennial meeting attendees, as reported in a Medscape Medical News profile piece some years ago.

This year the medical oncologist will also serve as the chair of the "View from the Trenches" session, which is devoted to summarizing the meeting's most important findings for everyday practitioners.

A number of years ago, Vogl proposed the idea of this where-the-rubber-meets-the-road session to SABCS meeting planners, which they then adopted. This year, Kaklamani invited Vogl to run the session and he accepted.

Vogl is a "really smart guy who is always right on" with his comments and questions, and he will be the first-ever independent, community-based oncologist to chair a meeting session, said Kaklamani.

COVID Sessions

On the meeting's first day, SABCS will feature a special session on COVID-19 and breast cancer. The meeting organizers sought to separate the wheat from the chaff in this subject, as much has already been written, published, or presented.

"We received a lot of abstracts on COVID that were studies that were poorly done. We tried to tease through them and select the well-researched ones," acknowledged Kaklamani.

The organizers included two patient advocates who have had COVID-19, including during treatment for breast cancer, as participants in the meeting session. The session will also feature global perspectives, with presenters from Brazil, Italy, and the Netherlands.

Plenary Lectures

The meeting's two plenary lectures will focus, respectively, on the increasingly used clinical approach of neoadjuvant therapy in breast cancer, and research in the time of a pandemic.

Elizabeth Mittendorf, MD, PhD, a surgical oncologist and director of the Breast lmmuno-Oncology program and co-director of the Breast Cancer Clinical Research Program at the Dana-Farber/Brigham and Women's Cancer Center, Boston, will present "Local Regional Management Following Neoadjuvant Therapy: Minding the Knowledge Gaps."

Ned Sharpless, MD, director of the National Cancer Institute (NCI), will present "Advancing Cancer Research During Challenging Times."

Kaklamani has disclosed consulting fees with Amgen, Eisai, Puma, Celldex, AstraZeneca, and Athenex; fees for non-CME services received directly from commercial interest or their agents from Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, and Novartis; and contracted research with Eisai.

https://www.medscape.com/viewarticle/942048

Pfizer said to seek emergency approval for COVID-19 vaccine in India

Pfizer Inc has applied for emergency use authorisation of its coronavirus vaccine in India, media said on Sunday, the first to do so in a country with the world’s second-highest number of infections.

The U.S. company, whose vaccine was recently approved by the British government, has written to the Drugs Controller General of India (DCGI), CNN-News18 reported citing a government source.

Officials at the DCGI and the health ministry did not respond to requests for comment. A government official, however, told Reuters that no application had been received as of Saturday night.

Indian officials have said they are pinning their hopes mainly on locally tested vaccines instead of those developed by Pfizer and Moderna Inc.

The Pfizer shot needs to be stored at minus 70 degrees Celsius (-94 F) or below, temperatures that most Indian cold storages cannot reach.

India has reported more 9.57 million COVID-19 cases, behind only the United States, with nearly 140,000 deaths.

https://www.reuters.com/article/us-health-coronavirus-pfizer-india/pfizer-seeks-emergency-approval-for-covid-19-vaccine-in-india-media-say-idUSKBN28G037

Why does the FDA need three weeks to approve Pfizer's vaccine?

In an op-ed for The Dispatch, Johns Hopkins Professor Marty Makary slammed the FDA for "holding up COVID-19 vaccine approval" and dubbed the agency's progress "Operation Turtle Speed."
"Pfizer (NYSE:PFE) submitted data detailing the safety and effectiveness of its vaccine on Nov. 22. But rather than immediately convening experts, the FDA scheduled a review meeting on Dec. 10, almost three weeks later. As Pfizer's application sits on the shelf at the FDA awaiting authorization, about 27,000 Americans will have died. So what is the FDA doing for three weeks?"
"Contrary to popular belief, the FDA process is not hands-on - it does not interview vaccine trial patients or look under a microscope at the immune cells. It's doing a statistical analysis and looking at data. For the vaccine trial, the data set is small and straightforward. If my research team, normally tasked with analyzing data on millions of patients, was asked to review the smaller Pfizer vaccine study of 43,000 patients, it would take about one hour."
"The FDA also reviews manufacturing data from Pfizer on how they made the drug. But not only can that data be reviewed in a few hours, it should have been done months ago when it was available. While the FDA was waiting for Pfizer’s long-term vaccine results to come in, the agency should have anticipated this step and done it early."
"The final step of the FDA review is to look at the outcomes of the study volunteers, including rates and severity of infection and side effects in the vaccine and placebo groups. Again, there is no plausible reason why this basic analysis cannot be done in 24 hours. The FDA and external scientists have a simple task: confirm or reject the review already conducted by the trial’s independent data safety monitoring board before FDA submission."
Note: Bahrain became the second country to grant emergency-use authorization to Pfizer and BioNTech's (NASDAQ:BNTX) vaccine on Friday. The U.K. became the first this past Wednesday.
https://seekingalpha.com/news/3641957-operation-turtle-speed-why-fda-need-three-weeks-to-approve-pfizers-vaccine

Saturday, December 5, 2020

CRISPR gene editing continues to show promise for two blood diseases

Ten patients with severe forms of the blood disorders sickle cell or beta thalassemia have all seen their condition improve after receiving an experimental treatment that genetically modified their cells, marking the latest step forward for a landmark technology known as CRISPR that won the Nobel Prize in Chemistry this year.

The results, showcased at a virtual meeting of the American Society of Hematology on Saturday, come from two pioneering early-stage trials of a treatment called CTX001 and developed by biotech partners CRISPR Therapeutics and Vertex.

In one study, seven beta thalassemia patients no longer needed blood transfusions for at least three months and as long as 20.5 months post-treatment. Those patients used a median of 15 infusions per year before receiving CTX001, according to a presentation of the results.

In the other trial, three sickle cell patients treated with CTX001 haven't experienced any instances of the excruciating pain episodes known as a vaso-occlusive crisis for at least three months and as long as about 17. Before joining the trial, they had a median of seven per year.

All 10 patients are also now producing "normal to near-normal" total levels of the oxygen-carrying protein hemoglobin, which is either missing or warped in people with severe beta thalassemia or sickle cell disease.

So far, the effects of treatment haven't diminished, the companies said, and results were consistent regardless of each patient's disease severity or underlying genetic characteristics. A report on the first two patients treated was published in the New England Journal of Medicine on Saturday.

"We have great hope that this can be a one-time treatment that's curative for life," said CRISPR Therapeutics CEO Sam Kulkarni, in an interview.

For many of the patients, results are still early, with follow-up for only three to six months. Whether the positive effects will wear off in some is uncertain, although the companies presented data to suggest benefit will be long-lasting.

Study participants will also continue to be watched for any safety problems. CRISPR and Vertex did report one serious side effect possibly related to CTX001, a case of a potentially life-threatening immune reaction known as hemophagocytic lymphohistiocytosis, which appeared associated with several other side effects.

The condition, which can occur following bone marrow transplants, resolved and Kulkarni said the patient is "doing fine."

"I would expect that it's unlikely that we see that [moving forward] or that it's related to the therapy," he contended. Most other adverse events were deemed mild to moderate and related to the chemotherapy regimen needed to prepare patients for treatment.

While CRISPR Therapeutics and Vertex are reporting data on 10 patients at ASH, nine others have now been treated with CTX001. The partner companies aim to seek approval once they've treated enough patients in the two ongoing studies, according to Kulkarni. The exact number needed to satisfy regulators is still being determined, but "we could make a strong case that we don't need a large number of patients" given the degree of benefit observed so far, he added.

Typically, new drugs require testing in hundreds or thousands of patients across several phases of study. With gene editing and gene therapy, however, the "effect size" of treatment can be quite large, and the biological rationale of treatment particularly clear, meaning companies can make a convincing case to regulators with far few patients treated.

The two gene therapies approved to date in the U.S., for example, were cleared following study in 41 and 36 patients, respectively.

Both of those treatments, called Luxturna and Zolgensma, use a different technology than CTX001, replacing rather than editing genes. The Food and Drug Administration hasn't yet specifically outlined the approval requirements for a CRISPR-based medicine, meaning CRISPR Therapeutics and Vertex are forging the path forward as they go.

CRISPR gene editing involves a two-part biological system that can delete or later DNA sequences with a precise cut. Its potential use as a medicine, diagnostic and drug discovery tool is enormous, and has led to the creation of a wave of new biotech companies. CRISPR Therapeutics, Editas Medicine and Intellia Therapeutics, for example, were each formed to advance CRISPR-based therapies.

In October, CRISPR Therapeutics co-founder Emmanuelle Charpentier and Intellia co-founder Jennifer Doudna were awarded a Nobel Prize for their work developing the gene editing method.

All three companies now have CRISPR-based therapies in human testing, but CTX001 is the first to produce results in a clinical trial.

Both beta thalassemia and sickle cell are caused by mutations in a gene that encodes for beta-globin, a protein that forms part of adult hemoglobin. With the gene damaged, individuals with either disease can't produce healthy hemoglobin, leading to anemia and a host of other health problems.

Many beta thalassemia patients depend on chronic blood transfusions, for example, but there are complications associated with that treatment, too. Sickle cell patients, meanwhile, have crescent-shaped blood cells that get lodged in blood vessels, triggering painful episodes that can require hospitalization.

The aim of CTX001 is to help patients make enough hemoglobin to free them from blood transfusions and pain crises. CTX001 consists of stem cells collected from a patient's bone marrow, which are then altered using CRISPR to encourage production of a form of hemoglobin that's present at birth but fades with age. The cells are then infused back into the body, where they take hold in the bone marrow and, in theory, churn out enough so-called fetal hemoglobin to change the course of the disease.

So far, that appears to be the case. Patients in both groups are producing meaningful levels of fetal hemoglobin, even in those individuals with genetic make-ups that make their disease more severe.

One patient with very severe beta thalassemia, for example, was producing 11.5 g/dL of hemoglobin — within the range of normal — as of a four-month follow-up evaluation conducted recently, said study investigator Haydar Frangoul, medical director of pediatric hematology and oncology at Sarah Cannon Research Institute, in a presentation.

CRISPR Therapeutics and Vertex's findings could put pressure on Bluebird bio, which won European approval for its gene therapy Zynteglo in beta thalassemia, but has hit multiple delays in the U.S. Bluebird's gene therapies have shown promise for both diseases, although the company has had to fine tune its approach in sickle cell. In beta thalassemia, Bluebird has the most data in patients with a less severe form.

The results also appear more varied from patient to patient. CRISPR Therapeutics and Vertex hope that gene editing may be more predictable and durable than gene replacement, but that hasn't been proven.

"I think gene editing will be looked at as a different class of medicines by regulators and by investigators," Kulkarni said.

https://www.biopharmadive.com/news/crispr-vertex-sickle-cell-thalassemia-ash-2020/591657/

J&J study shows multiple myeloma cell therapy to be strongly effective

An experimental cell therapy developed by Johnson & Johnson reduced or eliminated signs of multiple myeloma in nearly all of 94 patients treated in a mid-stage study, according to results presented Saturday at a virtual meeting of the American Society of Hematology.
After one year, 89% of patients were still alive and roughly three quarters were still responding to treatment, the data showed. The study presentation at ASH strengthens earlier findings, which were similarly encouraging.
The new data are from patients enrolled into an expansion portion of J&J's trial, called CARTITUDE-1. Participants were very sick, with their cancer having progressed following a median of six different treatments. While J&J's therapy appears strongly effective, side effects were common and one patient died from an adverse reaction typical of cell therapy treatment.

J&J's cell therapy is one of a broad slate of new medicines being developed for multiple myeloma that target a protein called BCMA, which is commonly found on diseased blood cells.

Blenrep, an antibody drug from GlaxoSmithKline, became the first such drug approved when the Food and Drug Administration cleared it in August.

Cell therapies like J&J's and another from Bristol Myers Squibb called ide-cel appear much more potent, inducing strong response rates. Both are CAR-T cell therapies, which involve the re-engineering of patients' own immune cells to seek out BCMA-expressing cancers.

Three CAR-T therapies are approved to treat leukemia and lymphoma, but ide-cel would be the first in multiple myeloma if approved as expected by March of next year.

The catch with CAR-T therapies is the process by which they are made is complicated, expensive and can sometimes fail. Both ide-cel and J&J's cell therapy, which the pharma licensed from China-based Legend Biotech, could face competition from other BCMA-targeting antibody drugs, a handful of which are in early- to mid-stage testing.

In CARTITUDE-1, treatment with J&J's therapy, cilta-cel, led to responses in 94 of 97 enrolled patients. Sixty-seven percent met the criteria for a "stringent complete response," meaning no signs of diseases cells were observed in the bone marrow.

At 12 months, 77% of patients showed no sign of their cancer progressing, and 89% were still alive.

J&J plans to submit the data from its trial to the Food and Drug Administration in the next weeks. But CARTITUDE-1 is only a first step in the drugmaker's planned work with cilta-cel in multiple myeloma, said Mark Wildgust, vice president of oncology global medical affairs with J&J.

"I think the CARTITUDE-1 data gives us confidence in [cilta-cel as a] single agent," he said in an interview. "Now we have to see if we can do it earlier in the disease."

One significant concern with CAR-T therapy is its side effect profile. Treatment is commonly associated with an immune system response known as "cytokine release syndrome," or CRS, and neurotoxicity.

Nearly all patients in J&J's trial experienced CRS, and one patient died from the condition. Ninety-five percent of those affected had symptoms mild enough to be managed with fever-reducing medications or, if hospital care was necessary, responded quickly to treatment, J&J said.

The company hopes cilta-cel could potentially be given as an outpatient treatment, a goal of many CAR-T drug developers. Whether J&J's data supports that approach will be up to Food and Drug Administration officials, who will look closely at the risks of allowing patients to go home after treatment.

A neurological side effect associated with CRS occurred in 16 patients, but subsided, at the median, four days following onset. Twelve other cases of neurotoxicity were also observed, with one being fatal, J&J said.

Also at ASH, Bristol Myers disclosed updated data from Phase 1 and 2 trials of ide-cel. In the early study, which included four different doses tested, results showed three-quarters of patients responded to treatment.

Median progression-free survival in that study stretched to nine months, and participants lived a median of 34 months post treatment.

An analysis of the later, pivotal KarMMa study showed more than two thirds of patients responded to treatment in most high-risk groups, Bristol Myers said, while median progression-free survival was longer than seven months.

Results presented earlier this year showed, across the entire KarMMa study, an overall response rate of 73%, which rose to 82% among those given the highest dose.

https://www.biopharmadive.com/news/johnson-johnson-car-t-multiple-myeloma/591659/