In a year that has seen impressive advances for cell and gene therapies, this weekend's annual meeting of the American Society of Hematology will showcase new findings for a range of treatments aimed at hard-to-treat blood disorders and cancers.
While updates on already approved CAR-T treatments look set to draw investor attention, ASH will also highlight the emergence of a second wave of T-cell therapies targeting B-cell maturation antigen (BCMA) in multiple myeloma. At the same time, gene therapies from Bluebird bio Inc. and BioMarin Pharmaceuticals Inc. are making strides in hemophilia and sickle cell disease.
For pharmas like AbbVie Inc. and Johnson & Johnson, ASH is an opportunity to build upon earlier foundations. For smaller biotechs, the meeting can be a tense exercise that sends share prices fluctuating.
The seven companies below look likely to feature in many headlines coming from the meeting, for better or for worse.
AbbVie (abstract #LBA-2)
BioMarin (abstract #603)
Juno Therapeutics (abstract #581)
Janssen Biotech (abstract #LBA-4)
Novartis (abstract #577)
Seattle Genetics (abstract #6)
AbbVie is best known for its top-selling immunology drug Humira (adalimumab). Yet the biopharma has simultaneously built a formidable business in hematologic malignancies.
The growing depth of that business will be on display next week at ASH, where AbbVie will present results from a closely watched Phase 3 study called MURANO.
In that study, AbbVie paired its BCL-2 inhibitor Venclexta (venetoclax) with Rituxan (rituximab) to treat patients with relapsed or refractory chronic lymphocytic leukemia (CLL). (Venclexta is jointly commercialized by AbbVie and Roches's Genentech Inc. in the U.S.)
Venclexta is already OK'd by the Food and Drug Administration for a more aggressive type of CLL marked by a chromosonal abnormality known as 17p deletion. The MURANO study is aimed at supporting an expanded approval in the broader relapsed and refractory population — a market potentially five times larger, according to Cowen & Co. analyst Steve Scala.
Data released in an abstract last month showed Venclexta plus Rituxan lowered the risk of disease progression or death by an impressive 83% compared to patients who received the common regimen of bendamustine and Rituxan.
That higher efficacy did come with the cost of a higher rate of neutropenia. But only six cases of Grade 3 or 4 tumor lysis syndrome, a known risk to Venclexta, were reported.
Success in MURANO marks a step forward in AbbVie's strategy to build Venclexta as a complementary treatment to Imbruvica (ibrutinib), which is already approved in first-line CLL.
Swiss pharma Roche AG may have current claim to the limelight in the hemophilia space with its recently approved Hemlibra (emicizumab).
But, as BioMarin will show at ASH, gene therapies for the inherited blood disorder are gaining momentum — promising potential one-time treatment in lieu of frequent Factor VIII infusions.
A press briefing at the conference will highlight both the now accessible improvement in care delivered by Hemlibra, as well as the future potential of BioMarin's gene therapy valoctocogene roxaparvovec (BMN 270).
While only from 13 patients, data from a Phase 1/2 study of BMN 270 showed injection of the corrected gene led to sustained Factor VIII activity. Ten patients across two dose cohorts self-reported no bleeding episodes from one month post-infusion through the last follow-up visit.
Just as it has been in past years, ASH will be a key milestone for Bluebird bio, which will present updates on its LentiGlobin gene therapy in sickle-cell disease and beta thalassemia, as well as for its closely watched CAR-T program bb2121.
In sickle cell disease, the focus will be on manufacturing changes the biotech made last fall to boost LentiGlobin’s potency. Data from two patients previewed ahead of the conference suggest those improvements have boosted transduction and engraftment efficacy of the genetically modified stem cells.
At ASH, look for new ex vivo data from patients in the sickle cell study's "Group C," which are treated using the improved drug product as well as a new method of stem cell collection.
Bluebird bio will also present results from its Northstar-2 trial of LentiGlobin in transfusion-dependent beta thalassemia. Follow-up results for three patients already treated, along with an estimated five others, will be included.
Yet, the biotech's CAR-T treatment for multiple myeloma, bb2121, might steal investor attention away from LentiGlobin. Sixteen of 18 heavily pre-treated patients who received the cell therapy experienced a response after one month, according to the study’s abstract.
Notably, all evaluable patients treated with the three highest doses of bb2121 saw a response — eight of which were sustained out to six months.
BCMA-targeting CAR-Ts like bb2121 look to be the next evolution for a fast-moving field, and Bluebird's data to date suggest the biotech will be among the leaders.
More than a year removed from a major safety setback, and eight months after shelving its once lead candidate, Juno Therapeutics Inc. will enter ASH with new momentum.
Data from a trial abstract released in November showed Juno's CAR-T therapy JCAR017 delivered competitive-looking efficacy and safety in diffuse large B-cell lymphoma, stoking optimism the biotech could eventually pull even with competitors Novartis AG and Gilead Sciences Inc.
Any chance of that is a year or more away, so ASH will an important check on Juno's progress.
The results from Juno’s TRANSCEND study, while early, showed treatment with JCAR017 led to a complete response in 22 of 55 efficacy-evaluable patients at three months — roughly on par with Novartis' Kymirah (tisagenlecleucel) and Gilead's Yescarta (axicabtagene ciloleucel) in DLBCL.
TRANSCEND study, efficacy
|# of patients||ORR||CR|
|Best overall response||68||75%||56%|
|At 3 months||55||49%||40%|
|At 6 months||35||40%||37%|
Juno believes JCAR017 could be potentially best in class, pointing to the therapy's defined cell composition as an advantage.
One area to watch will be the treatment's safety profile, with relatively lower rates of severe cytokine release syndrome and neurotoxicity reported. The company even says JCAR017 could possibly be administered as an outpatient therapy.
TRANSCEND study, safety
|Any grade CRS||30%|
|Any grade neurotoxicity||20%|
Juno will also present an abstract on its anti-BCMA CAR — known as JCARH125 — in multiple myeloma, which could attract investor attention given the promising data to date from other BMCA targeting CAR-Ts. Expect to see more data on response rates at three and six months, as well as on duration of response and overall survival.
Johnson & Johnson's pharma arm scored a late-breaking abstract entrant to this year's ASH with data from its ALYCONE study of Darzalex (daratumumab).
Combining the blood cancer drug with a combination regimen known as VMP effectively doubled progression-free survival compared to VMP alone in newly diagnosed multiple myeloma patients ineligible for transplant.
Darzalex is already an important growth driver for J&J in oncology, currently holding an approval in later lines of therapy for multiple myeloma.
The data set to be presented at ASH is important because it will likely support an expansion of Darzalex into the first-line setting and could further accelerate the drug's sales in the future.
Toward that end, J&J has requested priority review from the FDA for its supplemental Biologics License Application.
J&J's success with Darzalex, which it licenses from Genmab A/S, has even prompted speculation the healthcare giant might seek to acquire the Danish biotech outright rather than continue to pay royalties on sales.
While Novartis AG holds a U.S. approval for Kymriah in adult lymphocytic leukemia, the Swiss pharma is chasing Gilead's Yescarta in the larger market of DLBCL.
Results released at the International Conference on Malignant Lymphoma this past summer showcased the treatment’s competitive overall and complete response rates at three months. Investors will be watching Novartis' update at ASH to see data from more patients on how that efficacy holds up through six months.
From what was disclosed in the JULIET study abstract, the majority of patients who responded at three months appeared to remain so through the half-year mark.
The update is important because Gilead's Yescarta is already approved in DLBCL, having notched a 36% complete response rate among 101 patients at six months. Both treatments will be highlighted in a press conference that will also feature 12-month follow-up data for Yescarta.
Novartis already filed for approval of Kymriah in DLBCL back in October, setting up a decision from the FDA in 2018.
Shares in Seattle Genetics Inc. slid in June when the Seattle-based biotech revealed top-line results from its Phase 3 ECHELON-1 study of Adcetris (brentuximab vedotin) plus combination chemotherapy in classical Hodgkin lymphoma (cHL).
While the study was positive — showing the pairing improved progression-free survival over a four-drug chemo cocktail — safety data prompted investor concerns. Patients on the treatment arm experienced higher rates of febrile neutropenia and peripheral neuropathy, although dose modifications and prophylactic growth factors helped manage those safety events.
Replacing the chemotherapy agent bleomycin with Adcetris in the treatment combo, however, resulted in lower rates of pulmonary toxicity.
Through ECHELON-1, Seattle Genetics and its partner Takeda Pharmaceutical Company Ltd. hope to establish Adcetris as the regimen of choice for frontline treatment of cHL. Improving on the current standard of care is a noteworthy accomplishment, although some may question the degree of benefit given the higher risks.
The companies' presentation at ASH will give a more comprehensive accounting of the drug’s safety profile and benefit.