TESARO: Ovarian cancer med added to Cancer Drugs Fund in UK

• Inclusion in the Cancer Drugs Fund will give more women in England and Wales with recurrent, platinum-sensitive ovarian cancer access to ZEJULA via a managed access arrangement
• ZEJULA was launched in the private market in the UK at the end of 2017

TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, today announced the National Institute for Health and Care Excellence (NICE) will make ZEJULA^® (niraparib), the first PARP inhibitor shown to be effective in patients with a BRCA mutation as well as those without a BRCA mutation, available to women in England and Wales with recurrent platinum-sensitive ovarian cancer via the Cancer Drugs Fund (CDF)¹.  NICE has recommended ZEJULA via the CDF for women with a BRCA mutation who have received two lines of chemotherapy and in women without a BRCAmutation who have received two or more lines of chemotherapy.

“At TESARO, we continue to globalize our mission and bring transformative therapies to patients. We are pleased that NICE will now provide more women with recurrent ovarian cancer in England and Wales access to ZEJULA through the CDF,” said Orlando Oliveira, Senior Vice President and General Manager, TESARO International. “Through close partnership with both NICE and NHS, TESARO can now offer ZEJULA as an option for second-line maintenance treatment, regardless of a patient’s BRCA status.”

The CDF is a source of funding for cancer drugs in England, providing patients access to promising new oncology treatments while NHS England and NICE analyze any additionally requested data to inform a final reimbursement decision on a new treatment or indication. Overall survival data for ZEJULA are not yet available, and as a result NICE has recommended ZEJULA for use within the CDF while further data are collected². Interim funding is provided via the CDF, giving patients access to the treatment through a managed access arrangement.

“Recurrent ovarian cancer is an aggressive form of cancer where a key goal of treatment is to keep women in remission and off chemotherapy for as long as possible – allowing them the best chance for a good quality of life,” said Jonathan Ledermann, Professor of Medical Oncology at the University College London Cancer Institute. “ZEJULA offers the chance to delay this cancer from returning or progressing for months, and possibly years in some cases. It is a significant step forward. Crucially, this decision opens the door for many women who, until now, have not had the option of maintenance treatment with a PARP inhibitor.”

https://bit.ly/2xAXYR8

#ASCO18: Bluebird & Celgene CAR-T nears 1 year of survival in multiple myeloma

Bluebird Bio and Celgene have built upon their already impressive early-stage clinical responses in advanced multiple myeloma, now confirming that their bb2121 CAR-T therapy extended progression-free survival to just shy of one year in a new set of phase 1 data.

In 18 participants receiving larger infusions of 150 million CAR-T cells or more—engineered to target B-cell maturation antigen, or BCMA, a protein on the surface of certain myeloma cells—the dose-escalation study saw a median PFS of 11.8 months. Meanwhile, the 16 patients across the study who saw their disease go into remission demonstrated a median PFS of 17.7 months, according to the companies’ presentation Friday at the annual meeting of the American Society of Clinical Oncology in Chicago.

Additionally, the new data showed little difference in overall response rates between patients with low or high levels of BCMA expression at high doses, meaning that future patients will not need to be segmented or tested with a diagnostic—an important distinction to note as the two companies look to file bb2121 with the FDA before the end of 2019, Bluebird CEO Nick Leschly told FierceBiotech.

Last December, in a presentation at the American Society of Hematology’s annual meeting, the companies demonstrated an 86% overall response rate, with 56% of patients in remission nine months after a single dose.

Now, the study—which has been expanded from 21 to 43 patients—also showed no new safety signals, including severe or fatal cases of cytokine release syndrome or neurotoxicity. While 63% of patients had a CRS event, the companies described them as manageable.

“That safety profile is incredibly important,” Leschly said. “Not only because you want it for patients, but also if you want to consider using this treatment in earlier myeloma patients, which we certainly do.”

Currently, bb2121 is being tested in heavily-treated multiple myeloma patients whose disease had relapsed after becoming refractory to multiple standard therapies. Two deaths in the study had been reported at ASH, linked to cardiac arrest and myelodysplastic syndrome. Both patients had demonstrated complete responses at their last assessments.

This year, Bluebird and Celgene hope to begin pursuit of bb2121 in earlier indications, step-by-step, Leschly said—including a planned phase 3 trial in third-line multiple myeloma compared to a triplet regimen of daratumumab (Genmab and Janssen’s Darzalex) plus pomalidomide (Celgene’s Pomalyst) and dexamethasone, a corticosteroid.

After that, the companies plan to explore label expansions in second-line therapy, followed by exploration in newly diagnosed disease compared to stem cell transplants.

“We believe our profile of efficacy and safety is very conducive to starting to move earlier lines of treatment,” he said. “That’s ultimately where the game will be played.”

Enrollment in a pivotal phase 2 trial, KarMMa, is already underway, which will be used to support the expected 2019 filing in later lines of treatment. The study plans to examine overall response rate in 80 relapsed and refractory patients who have previously received three or more treatment regimens.

KarMMa’s design also dovetails nicely with the phase 1 results, Leschly described, with certain elements being baked into the protocol along the way, such as aims for the higher end of the dose range and no delineation based on BCMA expression.

“As you now have refined and more targeted doses, one could hope that this data would be as good, if not better, over time,” he said. “But that’s what we need to go show.”

https://bit.ly/2LeLLn3

FDA lifts partial hold on Bristol-Myers myeloma med study

Bristol-Myers Squibb Company (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) lifted a partial clinical hold placed on CA209-602 (CheckMate -602), a randomized, open-label Phase 3 study evaluating the addition of Opdivo (nivolumab) to pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. The decision follows consultation with the FDA and agreement on amendments to the study protocol.

Three trials evaluating Opdivo-based combinations in relapsed or refractory multiple myeloma were placed on partial clinical hold in September 2017 as an FDA precaution following risks identified in trials studying another anti–PD-1 agent, pembrolizumab, in patients with multiple myeloma. CheckMate -602 is the last of the three trials to have its partial clinical hold lifted following a similar FDA action announced in December 2017, when the agency lifted partial holds on CA209-039 (CheckMate -039) and CA204-142.

https://bit.ly/2xAjCEY

Own Agios For ‘The Next Several Years’: Piper

Agios Pharmaceuticals Inc AGIO 3.59%, a pharmaceutical company that focuses on the field cellular metabolism to treat cancer and rare genetic diseases, is a stock investors should “own for the next several years,” according to Piper Jaffray.

The Analyst

Piper Jaffray’s Tyler M. Van Buren initiated coverage of Agios Pharmaceuticals with an Overweight rating and $125 price target.

The Thesis

The bullish case for owning Agios’ stock is four-fold, Van Buren said in a note.

• Agios and its partner Celgene CELG 0.46% received approval for its idhifa therapyand so far the launch has “gone well” and represents $200 million in potential U.S. sales. The company’s tibsovo therapy is similar to idhifa and is under review but should be approved by the end of 2018 and generate another $100 to $150 million in potential sales.
• Idhifa and tibsovo have shown “encouraging data” in frontline AML, but Van Buren said the opportunities for the therapies will likely expand. Tibsovo, for example, is in a Phase 1 development cholangiocarcinoma and low-grade glioma.
• Phase 2 data for the company’s AG-348 for the treatment pf Pyruvate Kinase Deficiency is favorable so far and indicates a durable 3.4 g/dL increase of hemoglobin in 50 percent of PKD patients.
• Agios faces a “very large” potential opportunity with its AG-270 for MTAP-deleted tumors. The company is expected to show initial data by early 2019 the latest and could ultimately serve more than 100,000 patients with MTAP-deleted tumors.

https://bit.ly/2LeDq2R

What to look out for at ASCO

This week, cancer patients, oncologists and investors alike look ahead to the annual meeting of the American Society of Clinical Oncology (ASCO), which kicks off in Chicago on Friday.

In the run-up to what is usually thought of as the world’s foremost cancer meeting, with speculation increasing over what new insights might be revealed by the global pharma and biotech industries, we read the runes to provide our take on what to look out for.

After a quieter-than-usual event in 2017, early signs indicate that this year’s ASCO – the American counterpart to the meeting of the European Society of Medical Oncology (ESMO) – will provide pointers towards a number of key, potentially game-changing clinical trends.

Plenary session

Perhaps the first place to look for headline-grabbing news is the plenary session. This year’s session highlights the following four programs.

“Early signs indicate that this year’s ASCO will provide pointers towards a number of key, potentially game-changing clinical trends.”

TAILORx

A Phase III trial of chemoendocrine therapy versus endocrine therapy alone in certain breast cancer patients.

Report from European Paediatric Soft Tissue Sarcoma Study Group (EpSSG)

Looking at maintenance low-dose chemotherapy in patients with high-risk rhabdomyosarcoma, an aggressive and highly malignant form of cancer.

CARMENA

Results from a Phase III noninferiority study looking at cytoreductive nephrectomy followed by Sutent (sunitinib), versus Sutent alone in metastatic kidney cancer.

KEYNOTE-042

Keytruda (pembrolizumab) versus platinum-based chemotherapy as a first-line non-small cell lung cancer therapy.

Antibody-drug conjugates (ADC)

There is plenty of action on the ADC front this year.

There are currently two marketed ADCs, Adcetris (brentuximab vedotin), approved by the US Food and Drug Administration in 2011 and again in 2015, and Kadcyla (ado-trastuzumab emtansine), which has been marketed in the USA since 2013.

Adcetris developers Takeda Pharmaceutical (TYO: 4502) and Seattle Genetics (Nasdaq: SGEN) are still presenting positive Phase III data to build a case for the drug in Hodgkin’s lymphoma, although investors have been underwhelmed by its potential in this indication.

Roche’s (ROG: SIX) Kadcyla meanwhile has been successful in breast cancer, but has also struggled to gain the levels of reimbursement it requested in certain territories.

Immunomedics

Despite what might appear a thin record of success for this class of therapy, drugmakers are still plugging away, and there may be light at the end of the tunnel.

This year, many will be watching out for Phase I/II data from Immunomedics (Nasdaq: IMMU), related to its ADC candidate sacituzumab govitecan.

Activist shareholders scotched a deal, agreed around this time last year, for Seattle Genetics to gain rights to the therapy, which could be a challenger in  HR-positive/HER2-negative breast cancer.

Now going it alone, Immunomedics has taken longer to develop the candidate, only last week filing for regulatory approval in the USA. Nonetheless, markets have rewarded the firm with a near 200% increase in stock price for its efforts.

Other ADCs

Other firms to present data on ADCs this year include Astrazeneca (LSE: AZN), Immunogen (Nasdaq: IMGN), Menarini and Oxford Biotherapeutics.

Following on from the success of Kadcyla in breast cancer, Japanese pharma major Daiichi Sankyo (TYO: 4568), and fellow Tokyo-based firm Takeda (TYO: 4502) have results from their respective ADC candidates in this indication.

Daiichi is developing trastuzumab deruxtecan against HER2-positive breast cancer, and also U3-1402, another topoisomerase I inhibitor, against HER3-positive patients. Meanwhile Takeda and co-developer Mersana Therapeutics will offer data on XMT-1522.

Pfizer and AbbVie

AbbVie (NYSE: ABBV) and co-developer Pfizer (NYSE: PFE) will show overall response rate (ORR) and progression-free survival (PFS) data on cofetuzumab pelidotin, a PTK7-targeting ADC the firms believe has promise in various cancers.

For AbbVie, it could be the last chance to salvage some value from its $5.8 billion acquisitionof Stemcentryx, which the firm bought in 2016, largely to get its hands on leading ADC candidate Rova-T.

Extremely high hopes for Rova-T in lung cancer were dashed in dramatic fashion earlier this year, sending the Chicago native’s shares crashing.

While it’s probably too much to say the road to ADC success is littered with failures, there have been other high profile misses, including ADCT-502, which Switzerland’s ADC Therapeutics dropped in late April due to safety and tolerability issues.

It’s been a rough year for ADCs so far. For many of the firms mentioned here, ASCO 2018 could provide a platform to reinstil some hope for this approach.

I-O plus chemo combos

In recent months and years, there have been a slew of immuno-oncology trials, following on from the success of landmark checkpoint inhibitors and other immunomodulating therapies from Bristol-Myers Squibb (NYSE: BMY), Merck & Co (NYSE: MRK) and others.

Much of the recent activity has focused on combining established I-O therapies with chemotherapeutics, and data from ASCO 2018 look likely to enhance the potential for this therapeutic approach.

Merck has led the field here, with the first ever combo approval, and the firm has bet heavily on Keytruda (pembrolizumab), with billions invested in hundreds of trials.

Observers eagerly await results from the KEYNOTE-042 trial in lung cancer, to be presented at the plenary session, and will have to be patient until the curtain lifts to find out what the New Jersey-based firm has in store this year.

Merck is not the only one competing, however, with data from the CheckMate-227 trial to go on show, detailing that Bristol-Myers’ Opdivo (nivolumab) plus chemo reduced by 26% the relative risk of PFS, while results from a Roche (ROG: SIX) study will show impressive overall survival benefit.

Also look out for

Cemiplimab

Data from Regeneron Pharmaceuticals (Nasdaq: REGN) and Sanofi’s me-too checkpoint inhibitor cemiplimab. The firms are looking to offer the sixth therapy in this class, and have data showing a 47.5% response rate among certain patients.

The firms are hoping to show that blocking the PD-1 receptor is a better approach than stopping the PD-L1 ligand, as three of the current products on the market do.

Nerlynx (neratinib)

While Puma Biotechnology (Nasdaq: PBYI) has hit a rough patch in its regulatory efforts, the firm has data showing adjuvant use can improve invasive disease-free survival for some breast cancer patients. An exploratory analyses from the Phase III ExteNET trial provides useful learnings that may help to guide treatment practices to promote uptake.

https://bit.ly/2xDPPeP

ASCO’18: Blacks with Advanced Prostate Cancer With Chemo Have Equal Survival

An analysis of pooled data from nine randomized phase III trials of more than 8,000 men with advanced prostate cancer who received chemotherapy shows chances of survival are as good for black men as white men. The median survival was the same in black men and white men overall (21 months), but black men had a 19% lower risk for death than white men when researchers adjusted for various important risk factors that affect survival.

This is the largest analysis to date comparing black men and white men with advanced prostate cancer treated with chemotherapy, according to lead study author Susan Halabi, Ph.D., professor of biostatistics and bioinformatics at Duke University in Durham, NC. The findings will be featured in a press briefing today and presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.

“By pooling data across clinical trials, this study provided a unique opportunity to evaluate how race might affect prostate cancer response to treatment,” said Dr. Halabi. “This study underscores the importance of increasing the participation of racial minorities in clinical trials. Every patient who participates in a clinical trial contributes to improving care, and all patients should have the opportunity to receive needed therapies.”

In the United States, prostate cancer incidence rates are 60% higher among black men. In addition, black men are more likely to be diagnosed at a younger age, and with advanced-stage and higher-grade cancer. Despite an overall decline in prostate cancer deaths over the years, black men are twice as likely to die of the disease than white men.^1,2

Each of the nine clinical trials included too few black men to be able to determine if black men benefit from docetaxel/prednisone as much as white men. Prior studies have suggested that black men with advanced prostate cancer who received treatment had shorter overall survival than white men, but evidence has been inconsistent.

About the Study: Researchers analyzed data from 8,820 men with metastatic castration-resistant prostate cancer (mCRPC) who participated in nine different randomized, phase III clinical trials. In all trials, patients received chemotherapy docetaxel with prednisone or a regimen containing docetaxel (Taxotere®) and prednisone combined with other treatments. Of the 8,820 participants, 7,528 (85%) were white, 500 (6%) were black, and the rest were Asian or an unspecified race. Only black men and white men were included in this analysis (a total of 8,028 men) in order to test a prior hypothesis that black men had a worse survival than white men.

Because black men in the study had poor-prognostic factors, such as higher prostate-specific antigen (PSA) levels and worse performance status (a measure of a patient’s general well-being and ability to perform activities of daily living), the researchers conducted a multivariable analysis that compared outcomes in black men to white men with the same prognostic factors.

Key Findings: Despite differences in prognostic factors, the median overall survival was 21 months in black men and white men. Adjusting for prognostic factors, such as patient age, performance status, site of metastasis, PSA level, alkaline phosphatase and hemoglobin levels, researchers found that black men were 19% less likely than white men to die from any cause.

Next Steps: As all patients included in this study were eligible to be enrolled in clinical trials and had access to clinical trials, the lower risk of death in black men may reflect differences in the biology of the disease, or it may be that black men have better tolerability to docetaxel-prednisone combination, noted Dr. Halabi. The researchers are planning genomic analyses to evaluate if there are biologic variations that might explain differences in outcomes by race. Meanwhile, this research highlights the importance of enrolling underrepresented populations with advanced prostate cancer in future phase III clinical trials. This study received funding from Congressionally Directed Medical Research Programs.

Study at a Glance
Disease: Advanced prostate cancer
Trial Type: Pooled analysis of data from 9 phase III clinical trials of chemotherapy plus prednisone
Patients on Trials: 8,820
Primary Finding: No difference in overall survival between black men and white men
Secondary Finding(s): Adjusting for prognostic factors, black men were 19% less likely than white men to die

References:
1. Prostate Cancer. (2017, June 19). Retrieved from https://www.cdc.gov/cancer/prostate/statistics/race.htm
2. Cancer Stat Facts: Prostate Cancer. (n.d.). Retrieved from https://seer.cancer.gov/statfacts/html/prost.html

https://bit.ly/2LPoo4J

Stem cell-based phase I trial to repair spinal cord injuries called encouraging

Writing in the June 1 issue of Cell Stem Cell, researchers at University of California San Diego School of Medicine report that a first-in-human phase I clinical trial in which neural stem cells were transplanted into participants with chronic spinal cord injuries produced measurable improvement in three of four subjects, with no serious adverse effects.

“The primary purpose of this first trial was to assess safety. And no procedure-related complications were observed in any of the patients,” said Joseph Ciacci, MD, principal investigator and a neurosurgeon at UC San Diego Health. “Our results suggest the approach can be performed safely and early signs of efficacy warrant further exploration and dose escalation studies.”

The trial used a human spinal cord-derived neural stem cell line developed by Neuralstem, Inc, a biopharmaceutical company based in Maryland. Four trial participants with one- to two-year-old permanent injuries to T2-T12 thoracic vertebrae (located in the middle of the spine) received six injections, each containing 1.2 million neural stem cells.

In previous research, published in 2013 by Ciacci and co-author Martin Marsala, MD, professor in the Department of Anesthesiology at UC San Diego School of Medicine, stem cells were transplanted into rats with spinal cord injuries, resulting in neuronal regeneration and improvement in the animals’ functioning and mobility.

In the latest human clinical trial, the results (measured 18 to 27 months after transplantation) were not dramatic, but encouraging. Analysis of motor and sensory function and electrophysiology results showed improvement in three of the four participants.

“This is a small sample size, but the real strengths of this study are the extensive follow-up period, electrophysiological assessments and the timeline of treatment. Everyone was treated after a year of injury, meaning there was essentially no chance of spontaneous recovery,” said Ciacci. “Our primary objective was to provide proof of safety and tolerability of treatment. We’ve done that. These early signs of potential efficacy, combined with the promising results of earlier animal studies, argue for pressing ahead with new trials and greater doses to see if we can further accelerate repair and recovery.”

A second clinical trial is in development. Its focus will be subjects with cervical injuries.

More information: Erik Curtis et al, A First-in-Human, Phase I Study of Neural Stem Cell Transplantation for Chronic Spinal Cord Injury, Cell Stem Cell (2018). DOI: 10.1016/j.stem.2018.05.014

https://bit.ly/2sqd2fm